Mixed Topics

A new guideline from the World Health Organization on nonsugar sweeteners (NSSs) recommends not using them to control weight or reduce the risk for diabetes, heart disease, or cancer. These sweeteners include aspartame, acesulfame K, advantame, saccharine, sucralose, stevia, and stevia derivatives.

The recommendation is based on the findings of a systematic review that collected data from 283 studies in adults, children, pregnant women, and mixed populations.

The findings suggest that use of NSSs does not confer any long-term benefit in reducing body fat in adults or children. They also suggest that long-term use of NSSs may have potential undesirable effects.

To clarify, short-term NSS use results in a small reduction in body weight and body mass index in adults without significant effects on other measures of adiposity or cardiometabolic health, including fasting glucose, insulin, blood lipids, and blood pressure.

Conversely, on a long-term basis, results from prospective cohort studies suggest that higher NSS intake is associated with increased risk for type 2 diabetes, cardiovascular diseases, and all-cause mortality in adults (very low– to low-certainty evidence). 

Regarding the risk for cancer, results from case-control studies suggest an association between saccharine intake and bladder cancer (very low certainty evidence), but significant associations for other types of cancer were not observed in case-control studies or meta-analysis of prospective cohort studies.

Relatively fewer studies were found for children, and results were largely inconclusive.

Finally, results for pregnant women suggest that higher NSS intake is associated with increased risk for preterm birth (low-certainty evidence) and possibly adiposity in offspring (very low–certainty evidence).
 

Reducing sugar consumption

“Replacing free sugars with NSS does not help with weight control in the long-term. People need to consider other ways to reduce free sugars intake, such as consuming food with naturally occurring sugars, like fruit, or unsweetened food and beverages,” Francesco Branca, MD, PhD, WHO director of the department of nutrition and food safety, said in a press release. 

“NSSs are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health,” he added.
 

Applying the guideline

The recommendation applies to all people except individuals with preexisting diabetes and includes all synthetic and naturally occurring or modified nonnutritive sweeteners, said the WHO. 

The recommendation does not apply to personal care and hygiene products containing NSSs, such as toothpaste, skin cream, and medications, or to low-calorie sugars and sugar alcohols (polyols).

Because the link observed in the evidence between NSSs and disease outcomes might be confounded by the baseline characteristics of study participants and complicated patterns of NSS use, the recommendation has been assessed as “conditional” by the WHO. 

“This signals that policy decisions based on this recommendation may require substantive discussion in specific country contexts, linked for example to the extent of consumption in different age groups,” said the WHO press release. 

This article was translated from the Medscape French Edition . A version of the article appeared on Medscape.com.

A new guideline from the World Health Organization on nonsugar sweeteners (NSSs) recommends not using them to control weight or reduce the risk for diabetes, heart disease, or cancer. These sweeteners include aspartame, acesulfame K, advantame, saccharine, sucralose, stevia, and stevia derivatives.

The recommendation is based on the findings of a systematic review that collected data from 283 studies in adults, children, pregnant women, and mixed populations.

The findings suggest that use of NSSs does not confer any long-term benefit in reducing body fat in adults or children. They also suggest that long-term use of NSSs may have potential undesirable effects.

To clarify, short-term NSS use results in a small reduction in body weight and body mass index in adults without significant effects on other measures of adiposity or cardiometabolic health, including fasting glucose, insulin, blood lipids, and blood pressure.

Conversely, on a long-term basis, results from prospective cohort studies suggest that higher NSS intake is associated with increased risk for type 2 diabetes, cardiovascular diseases, and all-cause mortality in adults (very low– to low-certainty evidence). 

Regarding the risk for cancer, results from case-control studies suggest an association between saccharine intake and bladder cancer (very low certainty evidence), but significant associations for other types of cancer were not observed in case-control studies or meta-analysis of prospective cohort studies.

Relatively fewer studies were found for children, and results were largely inconclusive.

Finally, results for pregnant women suggest that higher NSS intake is associated with increased risk for preterm birth (low-certainty evidence) and possibly adiposity in offspring (very low–certainty evidence).
 

Reducing sugar consumption

“Replacing free sugars with NSS does not help with weight control in the long-term. People need to consider other ways to reduce free sugars intake, such as consuming food with naturally occurring sugars, like fruit, or unsweetened food and beverages,” Francesco Branca, MD, PhD, WHO director of the department of nutrition and food safety, said in a press release. 

“NSSs are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health,” he added.
 

Applying the guideline

The recommendation applies to all people except individuals with preexisting diabetes and includes all synthetic and naturally occurring or modified nonnutritive sweeteners, said the WHO. 

The recommendation does not apply to personal care and hygiene products containing NSSs, such as toothpaste, skin cream, and medications, or to low-calorie sugars and sugar alcohols (polyols).

Because the link observed in the evidence between NSSs and disease outcomes might be confounded by the baseline characteristics of study participants and complicated patterns of NSS use, the recommendation has been assessed as “conditional” by the WHO. 

“This signals that policy decisions based on this recommendation may require substantive discussion in specific country contexts, linked for example to the extent of consumption in different age groups,” said the WHO press release. 

This article was translated from the Medscape French Edition . A version of the article appeared on Medscape.com.

A new guideline from the World Health Organization on nonsugar sweeteners (NSSs) recommends not using them to control weight or reduce the risk for diabetes, heart disease, or cancer. These sweeteners include aspartame, acesulfame K, advantame, saccharine, sucralose, stevia, and stevia derivatives.

The recommendation is based on the findings of a systematic review that collected data from 283 studies in adults, children, pregnant women, and mixed populations.

The findings suggest that use of NSSs does not confer any long-term benefit in reducing body fat in adults or children. They also suggest that long-term use of NSSs may have potential undesirable effects.

To clarify, short-term NSS use results in a small reduction in body weight and body mass index in adults without significant effects on other measures of adiposity or cardiometabolic health, including fasting glucose, insulin, blood lipids, and blood pressure.

Conversely, on a long-term basis, results from prospective cohort studies suggest that higher NSS intake is associated with increased risk for type 2 diabetes, cardiovascular diseases, and all-cause mortality in adults (very low– to low-certainty evidence). 

Regarding the risk for cancer, results from case-control studies suggest an association between saccharine intake and bladder cancer (very low certainty evidence), but significant associations for other types of cancer were not observed in case-control studies or meta-analysis of prospective cohort studies.

Relatively fewer studies were found for children, and results were largely inconclusive.

Finally, results for pregnant women suggest that higher NSS intake is associated with increased risk for preterm birth (low-certainty evidence) and possibly adiposity in offspring (very low–certainty evidence).
 

Reducing sugar consumption

“Replacing free sugars with NSS does not help with weight control in the long-term. People need to consider other ways to reduce free sugars intake, such as consuming food with naturally occurring sugars, like fruit, or unsweetened food and beverages,” Francesco Branca, MD, PhD, WHO director of the department of nutrition and food safety, said in a press release. 

“NSSs are not essential dietary factors and have no nutritional value. People should reduce the sweetness of the diet altogether, starting early in life, to improve their health,” he added.
 

Applying the guideline

The recommendation applies to all people except individuals with preexisting diabetes and includes all synthetic and naturally occurring or modified nonnutritive sweeteners, said the WHO. 

The recommendation does not apply to personal care and hygiene products containing NSSs, such as toothpaste, skin cream, and medications, or to low-calorie sugars and sugar alcohols (polyols).

Because the link observed in the evidence between NSSs and disease outcomes might be confounded by the baseline characteristics of study participants and complicated patterns of NSS use, the recommendation has been assessed as “conditional” by the WHO. 

“This signals that policy decisions based on this recommendation may require substantive discussion in specific country contexts, linked for example to the extent of consumption in different age groups,” said the WHO press release. 

This article was translated from the Medscape French Edition . A version of the article appeared on Medscape.com.

The US Coast Guard (USCG) operates within the US Department of Homeland Security during times of peace and represents a force of > 55,000 active-duty service members (ADSMs), civilians, and reservists. ADSMs account for about 40,000 USCG personnel. The missions of the USCG include activities such as maritime law enforcement (drug interdiction), search and rescue, and defense readiness.¹ Akin to other US Department of Defense (DoD) services, USCG ADSMs are required to maintain medical readiness to maximize operational success.

Whereas the DoD centralizes its health care services at military treatment facilities, USCG health care tends to be dispersed to smaller clinics and sickbays across large geographic areas. The USCG operates 42 clinics of varying sizes and medical capabilities, providing outpatient, dentistry, pharmacy, laboratory, radiology, physical therapy, optometry, and other health care services. Many ADSMs are evaluated by a USCG medical officer in these outpatient clinics, and ADSMs may choose to fill prescriptions at the in-house pharmacy if present at that clinic.

The USCG has 14 field pharmacists. In addition to the standard dispensing role at their respective clinics, USCG pharmacists provide regional oversight of pharmaceutical services for USCG units within their area of responsibility (AOR). Therefore, USCG pharmacists clinically, operationally, and logistically support these regional assets within their AOR while serving the traditional pharmacist role. USCG pharmacists have access to ADSM electronic health records (EHRs) when evaluating prescription orders, similar to other ambulatory care settings.

New recruits and accessions into the USCG are first screened for disqualifying health conditions, and ADSMs are required to maintain medical readiness throughout their careers.² Therefore, this population tends to be younger and overall healthier compared with the general population. Equally important, medication errors or inappropriate prescribing in the ADSM group could negatively affect their duty status and mission readiness of the USCG in addition to exposing the ADSM to medication-related harms.

Duty status is an important and unique consideration in this population. ADSMs are expected to be deployable worldwide and physically and mentally capable of executing all duties associated with their position. Duty status implications and the perceived ability to stand watch are tied to an ADMS’s specialty, training, and unit role. Duty status is based on various frameworks like the USCG Medical Manual, Aeromedical Policy Letters, and other governing documents.³ Duty status determinations are initiated by privileged USCG medical practitioners and may be executed in consultation with relevant commands and other subject matter experts. An inappropriately dosed antibiotic prescription, for example, can extend the duration that an ADSM would be considered unfit for full duty due to prolonged illness. Accordingly, being on a limited duty status may negatively affect USCG total mission readiness as a whole. USCG pharmacists play a vital role in optimizing ADSMs’ medication therapies to ensure safety and efficacy.

Currently no published literature explores the number of medication interventions or the impact of those interventions made by USCG pharmacists. This study aimed to quantify the number, duty status impact, and replicability of medication interventions made by one pharmacist at the USCG Base Alameda clinic over 6 months.

Methods

As part of a USCG quality improvement study, a pharmacist tracked all medication interventions on a spreadsheet at USCG Base Alameda clinic from July 1, 2021, to December 31, 2021. The study defined a medication intervention as a communication with the prescriber with the intention to change the medication, strength, dose, dosage form, quantity, or instructions. Each intervention was subcategorized as either a drug therapy problem (DTP) or a non-DTP intervention. Interventions were divided into 7 categories.

Each DTP intervention was evaluated in a retrospective chart review by a panel of USCG pharmacists to assess for duty status severity and replicability. For duty status severity, the panel reviewed the intervention after considering patient-specific factors and determined whether the original prescribing (had there not been an intervention) could have reasonably resulted in a change of duty status for the ADSM from a fit for full duty (FFFD) status to a different duty status (eg, fit for limited duty [FFLD]). This duty status review factored in potential impacts across multiple positions and billets, including aviators (pilots) and divers. In addition, the panel, whose members all have prior community pharmacy experience, assessed replicability by determining whether the same intervention could have reasonably been made in the absence of access to the patient EHR, as would be common in a community pharmacy setting.

Interventions without an identified DTP were considered non-DTP interventions. These interventions involved recommendations for a more cost-effective medication or a similar in stock therapeutic option to minimize delay of patient care. The spreadsheet also included the date, medication name, medication class, specific intervention made, outcome, and other descriptive comments.

Results

During the 6-month period, 1751 prescriptions were dispensed at USCG Base Alameda pharmacy with 116 interventions (7%).

Among the DTP interventions, 26 (41%) dealt with an inappropriate dose, 13 (20%) were for medication omission, 7 (11%) for inappropriate dosage form, and 6 (9%) for excess medication (Table 2).

Discussion

This study is novel in examining the impact of a pharmacist’s medication interventions in a USCG ambulatory care practice setting. A PubMed literature search of the phrases “Coast Guard AND pharmacy” or “Coast Guard AND pharmacy AND intervention” yielded no results specific to pharmacy interventions in a USCG setting. However, the 2021 implementation of the enterprise-wide MHS GENESIS EHR may support additional tracking and analysis tools in the future.

Pharmacist interventions have been studied in diverse patient populations and practice settings, and most conclude that pharmacists make meaningful interventions at their respective organizations.^4-7 Many of these studies were conducted at open-door health care systems, whereas USCG clinics serve ADSMs nearly exclusively. The ADSM population tends to be younger and healthier due to age requirements and medical accession and retention standards.

It is important to recognize the value of a USCG pharmacist in identifying and rectifying potential medication errors, particularly those that may affect the ability to stand duty for ADSMs. An example intervention includes changing the daily starting dose of citalopram from the ordered 30 mg to the intended 10 mg. Inappropriately prescribed medication regimens may increase the incidence of adverse effects or prolong duration to therapeutic efficacy, which impairs the ability to stand duty. There were 3 circumstances where the prescriber had ordered the medication for an incorrect ADSM that were rectified by the pharmacist. If left unchanged, these errors could negatively affect the ADSM’s overall health, well-being, and duty status.

The acceptance rate for interventions in this study was 96%. The literature suggests a highly variable acceptance rate of pharmacist interventions when examined across various practice settings, health systems, and geographic locations.^8-10 This study’s comparatively high rate could be due to the pharmacist-prescriber relationships at USCG clinics. By virtue of colocatation and teamwork initiatives, the pharmacist has the opportunity to develop positive rapport with physicians, physician assistants, and other clinic staff.

Having access to EHRs allowed the pharmacist to make 18 of the DTP interventions. Chart access is not unique to the USCG and is common in other ambulatory care settings. Those 18 interventions, such as reconciling a prescription ordered as fluticasone/salmeterol but recorded in the EHR as “will prescribe montelukast,” were deemed possible because of EHR access. Such interventions could potentially be lost if ADSMs solely received their pharmaceutical care elsewhere.

USCG uses independent duty health services technicians (IDHSs) who practice in settings where a medical officer is not present, such as at smaller sickbays or aboard Coast Guard cutters. In this study, an IDHS had mistakenly created a medication order for the medical officer to sign for bupropion SR, when the ADSM had been taking and was intended to continue taking bupropion XL. This order was signed off by the medical officer, but this oversight was identified and corrected by the pharmacist before dispensing. This indicates that there is a vital educational role that the USCG pharmacist fulfills when working with health care team members within the AOR.

Equally important to consider are the non-DTP interventions. In a military setting, minimizations of delay in care are a high priority. There were 34 instances where the pharmacist made an intervention to recommend a similar therapeutic medication that was in stock to ensure that the ADSM had timely access to the medication without the need for prior authorization. In the context of short-notice, mission-critical deployments that may last for multiple months, recognizing medication shortages or other inventory constraints and recommending therapeutic alternatives ensures that the USCG can maintain a ready posture for missions in addition to providing timely and quality patient care.

Saving about $1700 over 6 months is also important. While this was not explicitly evaluated in the study, prescribers may not be acutely aware of medication pricing. There are often significant price differences between different formulations of the same medication (eg, naproxen delayed-release vs tablets). Because USCG pharmacists are responsible for ordering medications and managing their regional budget within the AOR, they are best poised to make cost-savings recommendations. These interventions suggest that USCG pharmacists must continue to remain actively involved in the patient care team alongside physicians, physician assistants, nurses, and corpsmen. Throughout this setting and in so many others, patients’ health outcomes improve when pharmacists are more engaged in the pharmacotherapy care plan.

Limitations

Currently, the USCG does not publish ADSM demographic or health-related data, making it difficult to evaluate these interventions in the context of age, gender, or type of disease. Accordingly, potential directions for future research include how USCG pharmacists’ interventions are stratified by duty station and initial diagnosis. Such studies may support future models where USCG pharmacists are providing targeted education to prescribers based on disease or medication classes.

This analysis may have limited applicability to other practice settings even within USCG. Most USCG clinics have a limited number of medical officers; indeed, many have only one, and clinics with pharmacies typically have 1 to 5 medical officers aboard. USCG medical officers have a multitude of other duties, which may impact prescribing patterns and pharmacist interventions. Statistical analyses were limited by the dearth of baseline data or comparative literature. Finally, the assessment of DTP interventions’ impact did not use an official measurement tool like the US Department of Veterans Affairs’ Safety Assessment Code matrix.¹¹ Instead, the study used the internal USCG pharmacist panel for the fitness for duty consideration as the main stratification of the DTP interventions’ duty status severity, because maintaining medical readiness is the top priority for a USCG clinic.

Conclusions

The multifaceted role of pharmacists in USCG clinics includes collaborating with the patient care team to make pharmacy interventions that have significant impacts on ADSMs’ wellness and the USCG mission. The ADSMs of this nation deserve quality medical care that translates into mission readiness, and the USCG pharmacy force stands ready to support that goal.

Acknowledgments

The authors acknowledge the contributions of CDR Christopher Janik, US Coast Guard Headquarters, and LCDR Darin Schneider, US Coast Guard D11 Regional Practice Manager, in the drafting of the manuscript.

The US Coast Guard (USCG) operates within the US Department of Homeland Security during times of peace and represents a force of > 55,000 active-duty service members (ADSMs), civilians, and reservists. ADSMs account for about 40,000 USCG personnel. The missions of the USCG include activities such as maritime law enforcement (drug interdiction), search and rescue, and defense readiness.¹ Akin to other US Department of Defense (DoD) services, USCG ADSMs are required to maintain medical readiness to maximize operational success.

Whereas the DoD centralizes its health care services at military treatment facilities, USCG health care tends to be dispersed to smaller clinics and sickbays across large geographic areas. The USCG operates 42 clinics of varying sizes and medical capabilities, providing outpatient, dentistry, pharmacy, laboratory, radiology, physical therapy, optometry, and other health care services. Many ADSMs are evaluated by a USCG medical officer in these outpatient clinics, and ADSMs may choose to fill prescriptions at the in-house pharmacy if present at that clinic.

The USCG has 14 field pharmacists. In addition to the standard dispensing role at their respective clinics, USCG pharmacists provide regional oversight of pharmaceutical services for USCG units within their area of responsibility (AOR). Therefore, USCG pharmacists clinically, operationally, and logistically support these regional assets within their AOR while serving the traditional pharmacist role. USCG pharmacists have access to ADSM electronic health records (EHRs) when evaluating prescription orders, similar to other ambulatory care settings.

New recruits and accessions into the USCG are first screened for disqualifying health conditions, and ADSMs are required to maintain medical readiness throughout their careers.² Therefore, this population tends to be younger and overall healthier compared with the general population. Equally important, medication errors or inappropriate prescribing in the ADSM group could negatively affect their duty status and mission readiness of the USCG in addition to exposing the ADSM to medication-related harms.

Duty status is an important and unique consideration in this population. ADSMs are expected to be deployable worldwide and physically and mentally capable of executing all duties associated with their position. Duty status implications and the perceived ability to stand watch are tied to an ADMS’s specialty, training, and unit role. Duty status is based on various frameworks like the USCG Medical Manual, Aeromedical Policy Letters, and other governing documents.³ Duty status determinations are initiated by privileged USCG medical practitioners and may be executed in consultation with relevant commands and other subject matter experts. An inappropriately dosed antibiotic prescription, for example, can extend the duration that an ADSM would be considered unfit for full duty due to prolonged illness. Accordingly, being on a limited duty status may negatively affect USCG total mission readiness as a whole. USCG pharmacists play a vital role in optimizing ADSMs’ medication therapies to ensure safety and efficacy.

Currently no published literature explores the number of medication interventions or the impact of those interventions made by USCG pharmacists. This study aimed to quantify the number, duty status impact, and replicability of medication interventions made by one pharmacist at the USCG Base Alameda clinic over 6 months.

Methods

As part of a USCG quality improvement study, a pharmacist tracked all medication interventions on a spreadsheet at USCG Base Alameda clinic from July 1, 2021, to December 31, 2021. The study defined a medication intervention as a communication with the prescriber with the intention to change the medication, strength, dose, dosage form, quantity, or instructions. Each intervention was subcategorized as either a drug therapy problem (DTP) or a non-DTP intervention. Interventions were divided into 7 categories.

Each DTP intervention was evaluated in a retrospective chart review by a panel of USCG pharmacists to assess for duty status severity and replicability. For duty status severity, the panel reviewed the intervention after considering patient-specific factors and determined whether the original prescribing (had there not been an intervention) could have reasonably resulted in a change of duty status for the ADSM from a fit for full duty (FFFD) status to a different duty status (eg, fit for limited duty [FFLD]). This duty status review factored in potential impacts across multiple positions and billets, including aviators (pilots) and divers. In addition, the panel, whose members all have prior community pharmacy experience, assessed replicability by determining whether the same intervention could have reasonably been made in the absence of access to the patient EHR, as would be common in a community pharmacy setting.

Interventions without an identified DTP were considered non-DTP interventions. These interventions involved recommendations for a more cost-effective medication or a similar in stock therapeutic option to minimize delay of patient care. The spreadsheet also included the date, medication name, medication class, specific intervention made, outcome, and other descriptive comments.

Results

During the 6-month period, 1751 prescriptions were dispensed at USCG Base Alameda pharmacy with 116 interventions (7%).

Among the DTP interventions, 26 (41%) dealt with an inappropriate dose, 13 (20%) were for medication omission, 7 (11%) for inappropriate dosage form, and 6 (9%) for excess medication (Table 2).

Discussion

This study is novel in examining the impact of a pharmacist’s medication interventions in a USCG ambulatory care practice setting. A PubMed literature search of the phrases “Coast Guard AND pharmacy” or “Coast Guard AND pharmacy AND intervention” yielded no results specific to pharmacy interventions in a USCG setting. However, the 2021 implementation of the enterprise-wide MHS GENESIS EHR may support additional tracking and analysis tools in the future.

Pharmacist interventions have been studied in diverse patient populations and practice settings, and most conclude that pharmacists make meaningful interventions at their respective organizations.^4-7 Many of these studies were conducted at open-door health care systems, whereas USCG clinics serve ADSMs nearly exclusively. The ADSM population tends to be younger and healthier due to age requirements and medical accession and retention standards.

It is important to recognize the value of a USCG pharmacist in identifying and rectifying potential medication errors, particularly those that may affect the ability to stand duty for ADSMs. An example intervention includes changing the daily starting dose of citalopram from the ordered 30 mg to the intended 10 mg. Inappropriately prescribed medication regimens may increase the incidence of adverse effects or prolong duration to therapeutic efficacy, which impairs the ability to stand duty. There were 3 circumstances where the prescriber had ordered the medication for an incorrect ADSM that were rectified by the pharmacist. If left unchanged, these errors could negatively affect the ADSM’s overall health, well-being, and duty status.

The acceptance rate for interventions in this study was 96%. The literature suggests a highly variable acceptance rate of pharmacist interventions when examined across various practice settings, health systems, and geographic locations.^8-10 This study’s comparatively high rate could be due to the pharmacist-prescriber relationships at USCG clinics. By virtue of colocatation and teamwork initiatives, the pharmacist has the opportunity to develop positive rapport with physicians, physician assistants, and other clinic staff.

Having access to EHRs allowed the pharmacist to make 18 of the DTP interventions. Chart access is not unique to the USCG and is common in other ambulatory care settings. Those 18 interventions, such as reconciling a prescription ordered as fluticasone/salmeterol but recorded in the EHR as “will prescribe montelukast,” were deemed possible because of EHR access. Such interventions could potentially be lost if ADSMs solely received their pharmaceutical care elsewhere.

USCG uses independent duty health services technicians (IDHSs) who practice in settings where a medical officer is not present, such as at smaller sickbays or aboard Coast Guard cutters. In this study, an IDHS had mistakenly created a medication order for the medical officer to sign for bupropion SR, when the ADSM had been taking and was intended to continue taking bupropion XL. This order was signed off by the medical officer, but this oversight was identified and corrected by the pharmacist before dispensing. This indicates that there is a vital educational role that the USCG pharmacist fulfills when working with health care team members within the AOR.

Equally important to consider are the non-DTP interventions. In a military setting, minimizations of delay in care are a high priority. There were 34 instances where the pharmacist made an intervention to recommend a similar therapeutic medication that was in stock to ensure that the ADSM had timely access to the medication without the need for prior authorization. In the context of short-notice, mission-critical deployments that may last for multiple months, recognizing medication shortages or other inventory constraints and recommending therapeutic alternatives ensures that the USCG can maintain a ready posture for missions in addition to providing timely and quality patient care.

Saving about $1700 over 6 months is also important. While this was not explicitly evaluated in the study, prescribers may not be acutely aware of medication pricing. There are often significant price differences between different formulations of the same medication (eg, naproxen delayed-release vs tablets). Because USCG pharmacists are responsible for ordering medications and managing their regional budget within the AOR, they are best poised to make cost-savings recommendations. These interventions suggest that USCG pharmacists must continue to remain actively involved in the patient care team alongside physicians, physician assistants, nurses, and corpsmen. Throughout this setting and in so many others, patients’ health outcomes improve when pharmacists are more engaged in the pharmacotherapy care plan.

Limitations

Currently, the USCG does not publish ADSM demographic or health-related data, making it difficult to evaluate these interventions in the context of age, gender, or type of disease. Accordingly, potential directions for future research include how USCG pharmacists’ interventions are stratified by duty station and initial diagnosis. Such studies may support future models where USCG pharmacists are providing targeted education to prescribers based on disease or medication classes.

This analysis may have limited applicability to other practice settings even within USCG. Most USCG clinics have a limited number of medical officers; indeed, many have only one, and clinics with pharmacies typically have 1 to 5 medical officers aboard. USCG medical officers have a multitude of other duties, which may impact prescribing patterns and pharmacist interventions. Statistical analyses were limited by the dearth of baseline data or comparative literature. Finally, the assessment of DTP interventions’ impact did not use an official measurement tool like the US Department of Veterans Affairs’ Safety Assessment Code matrix.¹¹ Instead, the study used the internal USCG pharmacist panel for the fitness for duty consideration as the main stratification of the DTP interventions’ duty status severity, because maintaining medical readiness is the top priority for a USCG clinic.

Conclusions

The multifaceted role of pharmacists in USCG clinics includes collaborating with the patient care team to make pharmacy interventions that have significant impacts on ADSMs’ wellness and the USCG mission. The ADSMs of this nation deserve quality medical care that translates into mission readiness, and the USCG pharmacy force stands ready to support that goal.

Acknowledgments

The authors acknowledge the contributions of CDR Christopher Janik, US Coast Guard Headquarters, and LCDR Darin Schneider, US Coast Guard D11 Regional Practice Manager, in the drafting of the manuscript.

The US Coast Guard (USCG) operates within the US Department of Homeland Security during times of peace and represents a force of > 55,000 active-duty service members (ADSMs), civilians, and reservists. ADSMs account for about 40,000 USCG personnel. The missions of the USCG include activities such as maritime law enforcement (drug interdiction), search and rescue, and defense readiness.¹ Akin to other US Department of Defense (DoD) services, USCG ADSMs are required to maintain medical readiness to maximize operational success.

Whereas the DoD centralizes its health care services at military treatment facilities, USCG health care tends to be dispersed to smaller clinics and sickbays across large geographic areas. The USCG operates 42 clinics of varying sizes and medical capabilities, providing outpatient, dentistry, pharmacy, laboratory, radiology, physical therapy, optometry, and other health care services. Many ADSMs are evaluated by a USCG medical officer in these outpatient clinics, and ADSMs may choose to fill prescriptions at the in-house pharmacy if present at that clinic.

The USCG has 14 field pharmacists. In addition to the standard dispensing role at their respective clinics, USCG pharmacists provide regional oversight of pharmaceutical services for USCG units within their area of responsibility (AOR). Therefore, USCG pharmacists clinically, operationally, and logistically support these regional assets within their AOR while serving the traditional pharmacist role. USCG pharmacists have access to ADSM electronic health records (EHRs) when evaluating prescription orders, similar to other ambulatory care settings.

New recruits and accessions into the USCG are first screened for disqualifying health conditions, and ADSMs are required to maintain medical readiness throughout their careers.² Therefore, this population tends to be younger and overall healthier compared with the general population. Equally important, medication errors or inappropriate prescribing in the ADSM group could negatively affect their duty status and mission readiness of the USCG in addition to exposing the ADSM to medication-related harms.

Duty status is an important and unique consideration in this population. ADSMs are expected to be deployable worldwide and physically and mentally capable of executing all duties associated with their position. Duty status implications and the perceived ability to stand watch are tied to an ADMS’s specialty, training, and unit role. Duty status is based on various frameworks like the USCG Medical Manual, Aeromedical Policy Letters, and other governing documents.³ Duty status determinations are initiated by privileged USCG medical practitioners and may be executed in consultation with relevant commands and other subject matter experts. An inappropriately dosed antibiotic prescription, for example, can extend the duration that an ADSM would be considered unfit for full duty due to prolonged illness. Accordingly, being on a limited duty status may negatively affect USCG total mission readiness as a whole. USCG pharmacists play a vital role in optimizing ADSMs’ medication therapies to ensure safety and efficacy.

Currently no published literature explores the number of medication interventions or the impact of those interventions made by USCG pharmacists. This study aimed to quantify the number, duty status impact, and replicability of medication interventions made by one pharmacist at the USCG Base Alameda clinic over 6 months.

Methods

As part of a USCG quality improvement study, a pharmacist tracked all medication interventions on a spreadsheet at USCG Base Alameda clinic from July 1, 2021, to December 31, 2021. The study defined a medication intervention as a communication with the prescriber with the intention to change the medication, strength, dose, dosage form, quantity, or instructions. Each intervention was subcategorized as either a drug therapy problem (DTP) or a non-DTP intervention. Interventions were divided into 7 categories.

Each DTP intervention was evaluated in a retrospective chart review by a panel of USCG pharmacists to assess for duty status severity and replicability. For duty status severity, the panel reviewed the intervention after considering patient-specific factors and determined whether the original prescribing (had there not been an intervention) could have reasonably resulted in a change of duty status for the ADSM from a fit for full duty (FFFD) status to a different duty status (eg, fit for limited duty [FFLD]). This duty status review factored in potential impacts across multiple positions and billets, including aviators (pilots) and divers. In addition, the panel, whose members all have prior community pharmacy experience, assessed replicability by determining whether the same intervention could have reasonably been made in the absence of access to the patient EHR, as would be common in a community pharmacy setting.

Interventions without an identified DTP were considered non-DTP interventions. These interventions involved recommendations for a more cost-effective medication or a similar in stock therapeutic option to minimize delay of patient care. The spreadsheet also included the date, medication name, medication class, specific intervention made, outcome, and other descriptive comments.

Results

During the 6-month period, 1751 prescriptions were dispensed at USCG Base Alameda pharmacy with 116 interventions (7%).

Among the DTP interventions, 26 (41%) dealt with an inappropriate dose, 13 (20%) were for medication omission, 7 (11%) for inappropriate dosage form, and 6 (9%) for excess medication (Table 2).

Discussion

This study is novel in examining the impact of a pharmacist’s medication interventions in a USCG ambulatory care practice setting. A PubMed literature search of the phrases “Coast Guard AND pharmacy” or “Coast Guard AND pharmacy AND intervention” yielded no results specific to pharmacy interventions in a USCG setting. However, the 2021 implementation of the enterprise-wide MHS GENESIS EHR may support additional tracking and analysis tools in the future.

Pharmacist interventions have been studied in diverse patient populations and practice settings, and most conclude that pharmacists make meaningful interventions at their respective organizations.^4-7 Many of these studies were conducted at open-door health care systems, whereas USCG clinics serve ADSMs nearly exclusively. The ADSM population tends to be younger and healthier due to age requirements and medical accession and retention standards.

It is important to recognize the value of a USCG pharmacist in identifying and rectifying potential medication errors, particularly those that may affect the ability to stand duty for ADSMs. An example intervention includes changing the daily starting dose of citalopram from the ordered 30 mg to the intended 10 mg. Inappropriately prescribed medication regimens may increase the incidence of adverse effects or prolong duration to therapeutic efficacy, which impairs the ability to stand duty. There were 3 circumstances where the prescriber had ordered the medication for an incorrect ADSM that were rectified by the pharmacist. If left unchanged, these errors could negatively affect the ADSM’s overall health, well-being, and duty status.

The acceptance rate for interventions in this study was 96%. The literature suggests a highly variable acceptance rate of pharmacist interventions when examined across various practice settings, health systems, and geographic locations.^8-10 This study’s comparatively high rate could be due to the pharmacist-prescriber relationships at USCG clinics. By virtue of colocatation and teamwork initiatives, the pharmacist has the opportunity to develop positive rapport with physicians, physician assistants, and other clinic staff.

Having access to EHRs allowed the pharmacist to make 18 of the DTP interventions. Chart access is not unique to the USCG and is common in other ambulatory care settings. Those 18 interventions, such as reconciling a prescription ordered as fluticasone/salmeterol but recorded in the EHR as “will prescribe montelukast,” were deemed possible because of EHR access. Such interventions could potentially be lost if ADSMs solely received their pharmaceutical care elsewhere.

USCG uses independent duty health services technicians (IDHSs) who practice in settings where a medical officer is not present, such as at smaller sickbays or aboard Coast Guard cutters. In this study, an IDHS had mistakenly created a medication order for the medical officer to sign for bupropion SR, when the ADSM had been taking and was intended to continue taking bupropion XL. This order was signed off by the medical officer, but this oversight was identified and corrected by the pharmacist before dispensing. This indicates that there is a vital educational role that the USCG pharmacist fulfills when working with health care team members within the AOR.

Equally important to consider are the non-DTP interventions. In a military setting, minimizations of delay in care are a high priority. There were 34 instances where the pharmacist made an intervention to recommend a similar therapeutic medication that was in stock to ensure that the ADSM had timely access to the medication without the need for prior authorization. In the context of short-notice, mission-critical deployments that may last for multiple months, recognizing medication shortages or other inventory constraints and recommending therapeutic alternatives ensures that the USCG can maintain a ready posture for missions in addition to providing timely and quality patient care.

Saving about $1700 over 6 months is also important. While this was not explicitly evaluated in the study, prescribers may not be acutely aware of medication pricing. There are often significant price differences between different formulations of the same medication (eg, naproxen delayed-release vs tablets). Because USCG pharmacists are responsible for ordering medications and managing their regional budget within the AOR, they are best poised to make cost-savings recommendations. These interventions suggest that USCG pharmacists must continue to remain actively involved in the patient care team alongside physicians, physician assistants, nurses, and corpsmen. Throughout this setting and in so many others, patients’ health outcomes improve when pharmacists are more engaged in the pharmacotherapy care plan.

Limitations

Currently, the USCG does not publish ADSM demographic or health-related data, making it difficult to evaluate these interventions in the context of age, gender, or type of disease. Accordingly, potential directions for future research include how USCG pharmacists’ interventions are stratified by duty station and initial diagnosis. Such studies may support future models where USCG pharmacists are providing targeted education to prescribers based on disease or medication classes.

This analysis may have limited applicability to other practice settings even within USCG. Most USCG clinics have a limited number of medical officers; indeed, many have only one, and clinics with pharmacies typically have 1 to 5 medical officers aboard. USCG medical officers have a multitude of other duties, which may impact prescribing patterns and pharmacist interventions. Statistical analyses were limited by the dearth of baseline data or comparative literature. Finally, the assessment of DTP interventions’ impact did not use an official measurement tool like the US Department of Veterans Affairs’ Safety Assessment Code matrix.¹¹ Instead, the study used the internal USCG pharmacist panel for the fitness for duty consideration as the main stratification of the DTP interventions’ duty status severity, because maintaining medical readiness is the top priority for a USCG clinic.

Conclusions

The multifaceted role of pharmacists in USCG clinics includes collaborating with the patient care team to make pharmacy interventions that have significant impacts on ADSMs’ wellness and the USCG mission. The ADSMs of this nation deserve quality medical care that translates into mission readiness, and the USCG pharmacy force stands ready to support that goal.

Acknowledgments

The authors acknowledge the contributions of CDR Christopher Janik, US Coast Guard Headquarters, and LCDR Darin Schneider, US Coast Guard D11 Regional Practice Manager, in the drafting of the manuscript.

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

A version of this article first appeared on Medscape.com.

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

A version of this article first appeared on Medscape.com.

Shortages of carboplatin and cisplatin have become widespread among major cancer centers, according to a survey released this week from the National Comprehensive Cancer Network.

The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.

“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.

“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”

The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.

“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.

Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.

The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.

The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.

“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”

In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:

• “Current shipments from established manufacturers have been paused.”
• “The supply of carboplatin available is not meeting our demands.”
• “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”

Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”

Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.

The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.

The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”

Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”

A version of this article first appeared on Medscape.com.

Springer Nature will retract an article that reported results of a survey of parents who thought their children’s gender dysphoria resulted from social contagion. The move is “due to concerns about lack of informed consent,” according to tweets by one of the paper’s authors. 

The article, “Rapid Onset Gender Dysphoria: Parent Reports on 1655 Possible Cases,” was published in March in the Archives of Sexual Behavior. It has not been cited in the scientific literature, according to Clarivate’s Web of Science, but Altmetric, which tracks the online attention papers receive, ranks the article in the top 1% of all articles of a similar age. 

Rapid Onset Gender Dysphoria (ROGD) is, the article stated, a “controversial theory” that “common cultural beliefs, values, and preoccupations cause some adolescents (especially female adolescents) to attribute their social problems, feelings, and mental health issues to gender dysphoria,” and that “youth with ROGD falsely believe that they are transgender,” in part due to social influences. 

Michael Bailey, a psychology professor at Northwestern University in Evanston, Ill., and the paper’s corresponding author, tweeted:

A version of this article first appeared on RetractionWatch.com.

Springer Nature will retract an article that reported results of a survey of parents who thought their children’s gender dysphoria resulted from social contagion. The move is “due to concerns about lack of informed consent,” according to tweets by one of the paper’s authors. 

The article, “Rapid Onset Gender Dysphoria: Parent Reports on 1655 Possible Cases,” was published in March in the Archives of Sexual Behavior. It has not been cited in the scientific literature, according to Clarivate’s Web of Science, but Altmetric, which tracks the online attention papers receive, ranks the article in the top 1% of all articles of a similar age. 

Rapid Onset Gender Dysphoria (ROGD) is, the article stated, a “controversial theory” that “common cultural beliefs, values, and preoccupations cause some adolescents (especially female adolescents) to attribute their social problems, feelings, and mental health issues to gender dysphoria,” and that “youth with ROGD falsely believe that they are transgender,” in part due to social influences. 

Michael Bailey, a psychology professor at Northwestern University in Evanston, Ill., and the paper’s corresponding author, tweeted:

A version of this article first appeared on RetractionWatch.com.

Springer Nature will retract an article that reported results of a survey of parents who thought their children’s gender dysphoria resulted from social contagion. The move is “due to concerns about lack of informed consent,” according to tweets by one of the paper’s authors. 

The article, “Rapid Onset Gender Dysphoria: Parent Reports on 1655 Possible Cases,” was published in March in the Archives of Sexual Behavior. It has not been cited in the scientific literature, according to Clarivate’s Web of Science, but Altmetric, which tracks the online attention papers receive, ranks the article in the top 1% of all articles of a similar age. 

Rapid Onset Gender Dysphoria (ROGD) is, the article stated, a “controversial theory” that “common cultural beliefs, values, and preoccupations cause some adolescents (especially female adolescents) to attribute their social problems, feelings, and mental health issues to gender dysphoria,” and that “youth with ROGD falsely believe that they are transgender,” in part due to social influences. 

Michael Bailey, a psychology professor at Northwestern University in Evanston, Ill., and the paper’s corresponding author, tweeted:

A version of this article first appeared on RetractionWatch.com.

An early predictor of cardiovascular disease (CVD) has been found in youth with bipolar disorder (BD), in new findings that may explain the “excessive and premature mortality” related to heart disease in this patient population.

The investigators found that higher reactive hyperemia index (RHI) scores, a measure of endothelial function, were tied to mood severity in patients with higher mania, but not depression scores. These findings persisted even after accounting for medications, obesity, and other cardiovascular risk factors (CVRFs).

“From a clinical perspective, these findings highlight the potential value of integrating vascular health in the assessment and management of youth with BD, and from a scientific perspective, these findings call for additional research focused on shared biological mechanisms linking vascular health and mood symptoms of BD,” senior investigator Benjamin Goldstein, MD, PhD, full professor of psychiatry, pharmacology, and psychological clinical science, University of Toronto, said in an interview.

The study was published online in the Journal of Clinical Psychiatry.
 

‘Excessively present’

BD is associated with “excessive and premature cardiovascular mortality” and CVD is “excessively present” in BD, exceeding what can be explained by traditional cardiovascular risk factors, psychiatric medications, and substance use, the researchers noted.

“In adults, more severe mood symptoms increase the risk of future CVD. Our focus on endothelial function rose due to the fact that CVD is rare in youth, whereas endothelial dysfunction – considered a precursor of CVD – can be assessed in youth,” said Dr. Goldstein, who holds the RBC Investments Chair in children’s mental health and developmental psychopathology at the Centre for Addiction and Mental Health, Toronto, where he is director of the Centre for Youth Bipolar Disorder.

For this reason, he and his colleagues were “interested in researching whether endothelial dysfunction is associated with mood symptoms in youth with BD.” Ultimately, the motivation was to “inspire new therapeutic opportunities that may improve both cardiovascular and mental health simultaneously.”

To investigate the question, the researchers studied 209 youth aged 13-20 years (n = 114 with BD and 94 healthy controls [HCs]).

In the BD group, there were 34 BD-euthymia, 36 BD-depressed, and 44 BD-hypomanic/mixed; and within the groups who had depression or hypomania/mixed features, 72 were experiencing clinically significant depression. 

Participants had to be free of chronic inflammatory illness, use of medications that might be addressing traditional CVRFs, recent infectious diseases, or neurologic conditions.

Participants’ bipolar symptoms, psychosocial functioning, and family history were assessed. In addition, they were asked about treatment, physical and/or sexual abuse, smoking status, and socioeconomic status. Height, weight, waist circumference, blood pressure, and blood tests to assess CVRFs, including C-reactive protein (CRP), were also assessed. RHI was measured via pulse amplitude tonometry, with lower values indicating poorer endothelial function.
 

Positive affect beneficial?

Compared with HCs, there were fewer White participants in the BD group (78% vs. 55%; P < .001). The BD group also had higher Tanner stage development scores (stage 5: 65% vs. 35%; P = .03; V = 0.21), higher body mass index (BMI, 24.4 ± 4.6 vs. 22.0 ± 4.2; P < .001; d = 0.53), and higher CRP (1.94 ± 3.99 vs. 0.76 ± 0.86; P = .009; d = –0.40).

After controlling for age, sex, and BMI (F_3,202 = 4.47; P = .005; n_p²  = 0.06), the researchers found significant between-group differences in RHI.

Post hoc pairwise comparisons showed RHI to be significantly lower in the BD-depressed versus the HC group (P = .04; d = 0.4). Moreover, the BD-hypomanic/mixed group had significantly higher RHI, compared with the other BD groups and the HC group.

RHI was associated with higher mania scores (beta, 0.26; P = .006), but there was no similar significant association with depression mood scores (beta, 0.01; P = .90).

The mood state differences in RHI and the RHI-mania association remained significant in sensitivity analyses examining the effect of current medication use as well as CVRFs, including lipids, CRP, and blood pressure on RHI.

“We found that youth with BD experiencing a depressive episode had lower endothelial function, whereas youth with BD experiencing a hypomanic/mixed episode had higher endothelial function, as compared to healthy youth,” Dr. Goldstein said.

There are several mechanisms potentially underlying the association between endothelial function and hypomania, the investigators noted. For example, positive affect is associated with increased endothelial function in normative samples, so hypomanic symptoms, including elation, may have similar beneficial associations, although those benefits likely do not extend to mania, which has been associated with cardiovascular risk.

They also point to several limitations in the study. The cross-sectional design “precludes making inferences regarding the temporal relationship between RHI and mood.” Moreover, the study focused only on hypomania, so “we cannot draw conclusions about mania.” In addition, the HC group had a “significantly higher proportion” of White participants, and a lower Tanner stage, so it “may not be a representative control sample.”

Nevertheless, the researchers concluded that the study “adds to the existing evidence for the potential value of integrating cardiovascular-related therapeutic approaches in BD,” noting that further research is needed to elucidate the mechanisms of the association.
 

Observable changes in youth

In a comment, Jess G Fiedorowicz, MD, PhD, head and chief, department of mental health, Ottawa Hospital Research Institute, noted that individuals with BD “have a much higher risk of CVD, which tends to develop earlier and shortens life expectancy by more than a decade.” 

This cardiovascular risk “appears to be acquired over the long-term course of illness and proportionate to the persistence and severity of mood symptoms, which implies that mood syndromes, such as depression and mania, themselves may induce changes in the body relevant to CVD,” said Dr. Fiedorowicz, who is also a professor in the department of psychiatry and senior research chair in adult psychiatry at the Brain and Mind Research Institute, University of Ottawa, and was not involved with the study.

The study “adds to a growing body of evidence that mood syndromes may enact physiological changes that may be relevant to risk of CVD. One important aspect of this study is that this can even be observed in young sample,” he said.

This study was funded by the Canadian Institutes of Health Research and a Miner’s Lamp Innovation Fund from the University of Toronto. Dr. Goldstein and coauthors declare no relevant financial relationships. Dr. Fiedorowicz receives an honorarium from Elsevier for his work as editor-in-chief of the Journal of Psychosomatic Research.

A version of this article first appeared on Medscape.com.

An early predictor of cardiovascular disease (CVD) has been found in youth with bipolar disorder (BD), in new findings that may explain the “excessive and premature mortality” related to heart disease in this patient population.

The investigators found that higher reactive hyperemia index (RHI) scores, a measure of endothelial function, were tied to mood severity in patients with higher mania, but not depression scores. These findings persisted even after accounting for medications, obesity, and other cardiovascular risk factors (CVRFs).

“From a clinical perspective, these findings highlight the potential value of integrating vascular health in the assessment and management of youth with BD, and from a scientific perspective, these findings call for additional research focused on shared biological mechanisms linking vascular health and mood symptoms of BD,” senior investigator Benjamin Goldstein, MD, PhD, full professor of psychiatry, pharmacology, and psychological clinical science, University of Toronto, said in an interview.

The study was published online in the Journal of Clinical Psychiatry.
 

‘Excessively present’

BD is associated with “excessive and premature cardiovascular mortality” and CVD is “excessively present” in BD, exceeding what can be explained by traditional cardiovascular risk factors, psychiatric medications, and substance use, the researchers noted.

“In adults, more severe mood symptoms increase the risk of future CVD. Our focus on endothelial function rose due to the fact that CVD is rare in youth, whereas endothelial dysfunction – considered a precursor of CVD – can be assessed in youth,” said Dr. Goldstein, who holds the RBC Investments Chair in children’s mental health and developmental psychopathology at the Centre for Addiction and Mental Health, Toronto, where he is director of the Centre for Youth Bipolar Disorder.

For this reason, he and his colleagues were “interested in researching whether endothelial dysfunction is associated with mood symptoms in youth with BD.” Ultimately, the motivation was to “inspire new therapeutic opportunities that may improve both cardiovascular and mental health simultaneously.”

To investigate the question, the researchers studied 209 youth aged 13-20 years (n = 114 with BD and 94 healthy controls [HCs]).

In the BD group, there were 34 BD-euthymia, 36 BD-depressed, and 44 BD-hypomanic/mixed; and within the groups who had depression or hypomania/mixed features, 72 were experiencing clinically significant depression. 

Participants had to be free of chronic inflammatory illness, use of medications that might be addressing traditional CVRFs, recent infectious diseases, or neurologic conditions.

Participants’ bipolar symptoms, psychosocial functioning, and family history were assessed. In addition, they were asked about treatment, physical and/or sexual abuse, smoking status, and socioeconomic status. Height, weight, waist circumference, blood pressure, and blood tests to assess CVRFs, including C-reactive protein (CRP), were also assessed. RHI was measured via pulse amplitude tonometry, with lower values indicating poorer endothelial function.
 

Positive affect beneficial?

Compared with HCs, there were fewer White participants in the BD group (78% vs. 55%; P < .001). The BD group also had higher Tanner stage development scores (stage 5: 65% vs. 35%; P = .03; V = 0.21), higher body mass index (BMI, 24.4 ± 4.6 vs. 22.0 ± 4.2; P < .001; d = 0.53), and higher CRP (1.94 ± 3.99 vs. 0.76 ± 0.86; P = .009; d = –0.40).

After controlling for age, sex, and BMI (F_3,202 = 4.47; P = .005; n_p²  = 0.06), the researchers found significant between-group differences in RHI.

Post hoc pairwise comparisons showed RHI to be significantly lower in the BD-depressed versus the HC group (P = .04; d = 0.4). Moreover, the BD-hypomanic/mixed group had significantly higher RHI, compared with the other BD groups and the HC group.

RHI was associated with higher mania scores (beta, 0.26; P = .006), but there was no similar significant association with depression mood scores (beta, 0.01; P = .90).

The mood state differences in RHI and the RHI-mania association remained significant in sensitivity analyses examining the effect of current medication use as well as CVRFs, including lipids, CRP, and blood pressure on RHI.

“We found that youth with BD experiencing a depressive episode had lower endothelial function, whereas youth with BD experiencing a hypomanic/mixed episode had higher endothelial function, as compared to healthy youth,” Dr. Goldstein said.

There are several mechanisms potentially underlying the association between endothelial function and hypomania, the investigators noted. For example, positive affect is associated with increased endothelial function in normative samples, so hypomanic symptoms, including elation, may have similar beneficial associations, although those benefits likely do not extend to mania, which has been associated with cardiovascular risk.

They also point to several limitations in the study. The cross-sectional design “precludes making inferences regarding the temporal relationship between RHI and mood.” Moreover, the study focused only on hypomania, so “we cannot draw conclusions about mania.” In addition, the HC group had a “significantly higher proportion” of White participants, and a lower Tanner stage, so it “may not be a representative control sample.”

Nevertheless, the researchers concluded that the study “adds to the existing evidence for the potential value of integrating cardiovascular-related therapeutic approaches in BD,” noting that further research is needed to elucidate the mechanisms of the association.
 

Observable changes in youth

In a comment, Jess G Fiedorowicz, MD, PhD, head and chief, department of mental health, Ottawa Hospital Research Institute, noted that individuals with BD “have a much higher risk of CVD, which tends to develop earlier and shortens life expectancy by more than a decade.” 

This cardiovascular risk “appears to be acquired over the long-term course of illness and proportionate to the persistence and severity of mood symptoms, which implies that mood syndromes, such as depression and mania, themselves may induce changes in the body relevant to CVD,” said Dr. Fiedorowicz, who is also a professor in the department of psychiatry and senior research chair in adult psychiatry at the Brain and Mind Research Institute, University of Ottawa, and was not involved with the study.

The study “adds to a growing body of evidence that mood syndromes may enact physiological changes that may be relevant to risk of CVD. One important aspect of this study is that this can even be observed in young sample,” he said.

This study was funded by the Canadian Institutes of Health Research and a Miner’s Lamp Innovation Fund from the University of Toronto. Dr. Goldstein and coauthors declare no relevant financial relationships. Dr. Fiedorowicz receives an honorarium from Elsevier for his work as editor-in-chief of the Journal of Psychosomatic Research.

A version of this article first appeared on Medscape.com.

An early predictor of cardiovascular disease (CVD) has been found in youth with bipolar disorder (BD), in new findings that may explain the “excessive and premature mortality” related to heart disease in this patient population.

The investigators found that higher reactive hyperemia index (RHI) scores, a measure of endothelial function, were tied to mood severity in patients with higher mania, but not depression scores. These findings persisted even after accounting for medications, obesity, and other cardiovascular risk factors (CVRFs).

“From a clinical perspective, these findings highlight the potential value of integrating vascular health in the assessment and management of youth with BD, and from a scientific perspective, these findings call for additional research focused on shared biological mechanisms linking vascular health and mood symptoms of BD,” senior investigator Benjamin Goldstein, MD, PhD, full professor of psychiatry, pharmacology, and psychological clinical science, University of Toronto, said in an interview.

The study was published online in the Journal of Clinical Psychiatry.
 

‘Excessively present’

BD is associated with “excessive and premature cardiovascular mortality” and CVD is “excessively present” in BD, exceeding what can be explained by traditional cardiovascular risk factors, psychiatric medications, and substance use, the researchers noted.

“In adults, more severe mood symptoms increase the risk of future CVD. Our focus on endothelial function rose due to the fact that CVD is rare in youth, whereas endothelial dysfunction – considered a precursor of CVD – can be assessed in youth,” said Dr. Goldstein, who holds the RBC Investments Chair in children’s mental health and developmental psychopathology at the Centre for Addiction and Mental Health, Toronto, where he is director of the Centre for Youth Bipolar Disorder.

For this reason, he and his colleagues were “interested in researching whether endothelial dysfunction is associated with mood symptoms in youth with BD.” Ultimately, the motivation was to “inspire new therapeutic opportunities that may improve both cardiovascular and mental health simultaneously.”

To investigate the question, the researchers studied 209 youth aged 13-20 years (n = 114 with BD and 94 healthy controls [HCs]).

In the BD group, there were 34 BD-euthymia, 36 BD-depressed, and 44 BD-hypomanic/mixed; and within the groups who had depression or hypomania/mixed features, 72 were experiencing clinically significant depression. 

Participants had to be free of chronic inflammatory illness, use of medications that might be addressing traditional CVRFs, recent infectious diseases, or neurologic conditions.

Participants’ bipolar symptoms, psychosocial functioning, and family history were assessed. In addition, they were asked about treatment, physical and/or sexual abuse, smoking status, and socioeconomic status. Height, weight, waist circumference, blood pressure, and blood tests to assess CVRFs, including C-reactive protein (CRP), were also assessed. RHI was measured via pulse amplitude tonometry, with lower values indicating poorer endothelial function.
 

Positive affect beneficial?

Compared with HCs, there were fewer White participants in the BD group (78% vs. 55%; P < .001). The BD group also had higher Tanner stage development scores (stage 5: 65% vs. 35%; P = .03; V = 0.21), higher body mass index (BMI, 24.4 ± 4.6 vs. 22.0 ± 4.2; P < .001; d = 0.53), and higher CRP (1.94 ± 3.99 vs. 0.76 ± 0.86; P = .009; d = –0.40).

After controlling for age, sex, and BMI (F_3,202 = 4.47; P = .005; n_p²  = 0.06), the researchers found significant between-group differences in RHI.

Post hoc pairwise comparisons showed RHI to be significantly lower in the BD-depressed versus the HC group (P = .04; d = 0.4). Moreover, the BD-hypomanic/mixed group had significantly higher RHI, compared with the other BD groups and the HC group.

RHI was associated with higher mania scores (beta, 0.26; P = .006), but there was no similar significant association with depression mood scores (beta, 0.01; P = .90).

The mood state differences in RHI and the RHI-mania association remained significant in sensitivity analyses examining the effect of current medication use as well as CVRFs, including lipids, CRP, and blood pressure on RHI.

“We found that youth with BD experiencing a depressive episode had lower endothelial function, whereas youth with BD experiencing a hypomanic/mixed episode had higher endothelial function, as compared to healthy youth,” Dr. Goldstein said.

There are several mechanisms potentially underlying the association between endothelial function and hypomania, the investigators noted. For example, positive affect is associated with increased endothelial function in normative samples, so hypomanic symptoms, including elation, may have similar beneficial associations, although those benefits likely do not extend to mania, which has been associated with cardiovascular risk.

They also point to several limitations in the study. The cross-sectional design “precludes making inferences regarding the temporal relationship between RHI and mood.” Moreover, the study focused only on hypomania, so “we cannot draw conclusions about mania.” In addition, the HC group had a “significantly higher proportion” of White participants, and a lower Tanner stage, so it “may not be a representative control sample.”

Nevertheless, the researchers concluded that the study “adds to the existing evidence for the potential value of integrating cardiovascular-related therapeutic approaches in BD,” noting that further research is needed to elucidate the mechanisms of the association.
 

Observable changes in youth

In a comment, Jess G Fiedorowicz, MD, PhD, head and chief, department of mental health, Ottawa Hospital Research Institute, noted that individuals with BD “have a much higher risk of CVD, which tends to develop earlier and shortens life expectancy by more than a decade.” 

This cardiovascular risk “appears to be acquired over the long-term course of illness and proportionate to the persistence and severity of mood symptoms, which implies that mood syndromes, such as depression and mania, themselves may induce changes in the body relevant to CVD,” said Dr. Fiedorowicz, who is also a professor in the department of psychiatry and senior research chair in adult psychiatry at the Brain and Mind Research Institute, University of Ottawa, and was not involved with the study.

The study “adds to a growing body of evidence that mood syndromes may enact physiological changes that may be relevant to risk of CVD. One important aspect of this study is that this can even be observed in young sample,” he said.

This study was funded by the Canadian Institutes of Health Research and a Miner’s Lamp Innovation Fund from the University of Toronto. Dr. Goldstein and coauthors declare no relevant financial relationships. Dr. Fiedorowicz receives an honorarium from Elsevier for his work as editor-in-chief of the Journal of Psychosomatic Research.

A version of this article first appeared on Medscape.com.

A deeper understanding of the mechanisms underlying the success of fecal microbiota transplantation (FMT) is needed to further improve its effectiveness, according to two recent reviews published in Cell Host and Microbe.

Both research teams agree that more needs to be known about how various underexplored factors – such as the patient’s diet and genetic background, how closely the donor’s microbial composition matches the patient’s existing microbiome, and the presence of nonbacterial gut inhabitants like viruses and fungi – affect FMT success, according to a press release.

FMT is most often used to treat recurrent Clostridioides difficile infections, which don’t always respond to antibiotics. Success rates range from 60% to 90%, depending on the administration route and study design, notes an international research team led by Abbas Yadegar, PhD, a medical bacteriologist at the Shahid Beheshti University of Medical Sciences in Tehran, Iran.

The understanding of how FMT works is incomplete, however, and the reasons some patients fail to benefit is unclear, note Dr. Yadegar and colleagues. Little attention has been paid to the role that other components of the patient’s microbiome, along with outside factors, play in the treatment’s success, they add.

“We wanted other researchers to look beyond changes in stool microbial composition and function, which have been the focus of research in the past few years,” Dr. Yadegar’s team said in a statement provided to this news organization.

Dr. Yadegar and colleagues’ review of more than 130 studies summarizes recent evidence on the mechanisms contributing to FMT success against recurrent C. difficile infection, highlights knowledge gaps, and proposes future research directions in the field.

Factors that influence FMT’s effectiveness and the potential the procedure holds for treatment of other diseases associated with gut dysbiosis are the subject of a review of 149 studies by a team of researchers led by Serena Porcari, MD, a gastroenterologist at the Fondazione Policlinico Universitario Gemelli and Università Cattolica del Sacro Cuore, in Rome.

“Our main goal was not only to unravel the different mechanisms of FMT efficacy but also to introduce some mindset shifts that are needed to bring FMT forward, mainly covering the gap that exists between basic scientists and clinicians,” Gianluca Ianiro, MD, PhD, a senior researcher in digestive diseases who works with Dr. Porcari and is the review’s lead author, told this news organization.
 

Engraftment may influence success

Engraftment of donor microbial strains in recipients appears to be key to the therapeutic success of FMT, both reviews note.

Three factors influence engraftment: the donor’s bacteria fitness relative to the recipient, the bacteria already present in the recipient, and whether antibiotics are used prior to FMT to open a niche for the incoming donor microbes, according to Dr. Yadegar and colleagues.

How to calculate strain engraftment has not yet been standardized in the field, and the number of strains detected in the recipient’s fecal sample is dependent on the depth of sequencing techniques, Dr. Porcari and colleagues note.

The use of whole-genome sequencing has enabled more precise evaluation of engraftment, they add.

“With this approach, microbial engraftment has been associated with clinical success, regardless of the disease, in a large metagenomic metanalysis of 24 FMT trials and almost 1,400 fecal samples,” Dr. Porcari and colleagues write. However, these results have not been replicated, likely because of differences between the studies.

More study on the topic is needed, both articles note.

“Because the recent metagenomics studies compared pre- and post-FMT only in cases with successful treatment outcomes, it is not possible to link engraftment to clinical outcomes,” Dr. Yadegar and colleagues write in their statement to this news organization.
 

A closer look at donor-recipient pairings

Clinicians usually enlist healthy, carefully screened individuals as FMT donors.

However, both research groups conclude that fine-scale taxonomic and metabolic analyses of donor and recipient microbiomes would better inform clinical decisions, especially when treating diseases other than C. difficile.

This may call for a more personalized approach to choosing donor-recipient pairings. Investigators should assess the patient’s diet and genetic background and how closely the donor’s microbiome matches that of the patient.

“Most studies focused on profiling stool samples before and after FMT without also including functional analyses; therefore, there are still a lot of aspects of host microbial interactions that remain unknown,” write Dr. Yadegar and colleagues in their statement.

Ecologic factors, including diet and host genetics, are often not included in clinical studies of C. difficile, but they “may potentially be the missing links” to treatment failure in the small portion of patients whose condition doesn’t respond to FMT, they write.

Pairing donor-recipient combinations on the basis of dietary patterns and preferences could improve FMT efficacy because the donor microbiota would be preadapted to the recipient’s diet, Dr. Yadegar and colleagues write. The team is examining how donor and recipient diet may affect outcomes.

Dr. Porcari and colleagues add that while some studies support the existence of shared characteristics that make up super-donors, others found that the optimal donor is more patient specific. They call for personalized selection strategies that employ microbiome sequencing tools rather than a “one stool fits all” approach.

Currently, many clinicians aren’t familiar with microbiome sequencing and analysis, but they’ll need to be in the near future, note Dr. Porcari and colleagues.

“Identifying microbiome characteristics that maximize strain engraftment in the FMT will allow clinicians to select the best donor for each single patient,” they write.
 

The possible role of viruses and fungi

In FMT research, investigators tend to focus on the bacteria in the human microbiome. However, viruses and fungi also appear to play a role, both articles note.

“Other microbial kingdoms that inhabit the intestine should be taken into account when considering predictors of post-FMT microbial transfer,” write Dr. Porcari and colleagues.

Although few studies have examined the gut virome’s impact on FMT effectiveness against C. difficile, the existing research, although limited, indicates that bacteriophage viruses could play a role, Dr. Yadegar and colleagues note. For example, high levels of donor-derived Caudoviralesbacteriophages in recipients were associated with FMT efficacy in one preliminary study, they write.

In a small human study, fecal filtrate from healthy donors who had bacteriophages but no live bacteria successfully treated five patients with recurrent C. difficile infection, Dr. Yadegar and colleagues write.

“Therefore, the idea that viruses may play a role is very provocative,” write Dr. Yadegar’s team in their statement.

It’s important to note that these studies are associative, which means they can’t definitively answer the question of how or whether viruses play a role, Dr. Yadegar’s team added.

Researchers “know even less about how fungi may or may not play a role,” write Dr. Yadegar and colleagues. However, in early research that involved patients who had successfully undergone FMT for C. difficile, there was higher relative abundance of Saccharomyces and Aspergillus, whereas Candida, if prominent, may impede response, they write in their article.

Additionally, to explore whether live bacteria are necessary for FMT to work, Dr. Yadegar and colleagues informed this news organization that they are conducting a study “comparing traditional FMT to a fecal filtrate that contains no live bacteria, but has all other components, to see if we can achieve similar success rates in recurrent C. difficile infection.”
 

Repeat treatment for sustained response

Dr. Yadegar’s team offered another important takeaway: A single FMT treatment will not sustain a positive response, especially when treating chronic noncommunicable conditions in which intestinal dysbiosis may play a role. Repeat treatment will be needed, as with other chronic conditions. This has been shown even in C. difficile infection.

“Recent studies have documented a significant advantage of repeated FMT over single FMT on the cure rates of recurrent C. difficile,” especially for patients with inflammatory bowel disorder, Dr. Yadegar’s team told this news organization.

“What we don’t know is which patient is likely to respond to microbial-based therapy, or what the dose or frequency should be, or which bacteria are responsible for the effects,” Dr. Yadegar and team said.

Dr. Porcari and colleagues are examining whether FMT could be refined to improve its success against other diseases. This may involve selecting specific donors, monitoring the gut microbiome of both donors and recipients, or using a specific means of delivery, such as lyophilized capsules, Dr. Ianiro said.

A response to FMT for chronic, noncommunicable disorders typically is not sustained long term, note Dr. Porcari and colleagues. However, they add that “sequential transplants have been applied in this setting with promising results, suggesting that chronic modulation of the patient microbiome may be beneficial in noncommunicable chronic disorders.” Dr. Porcari and colleagues point to the success of repeated, long-term FMT in studies of patients with ulcerative colitis and irritable bowel syndrome.

The use of cutting-edge technologies for microbiome assessment and a change in the view of FMT as only an acute, single-use therapy could improve FMT protocols and outcomes for noncommunicable conditions, they write.
 

Expanding FMT beyond C. difficile

Dr. Yadegar and colleagues’ article “really breaks down what is known about the mechanisms of FMT in C. difficile infection, which is important as other live biotherapeutic products are developed,” Colleen Kelly, MD, an associate professor of medicine at Brown University in Providence, R.I., who was not involved with the reviews, said in an interview.

Dr. Yadegar and colleagues concur. They note in a press release that as the mechanisms behind FMT success are understood, that information should be used to design new standardized therapies.

“Although highly effective, there are substantial drawbacks with [FMT], including infectious risks and sparse long-term safety data,” they write. “Better treatment options for recurrent C. difficile infections that are targeted, safe, and donor-independent are thus desired.”

In December 2022, the U.S. Food and Drug Administration approved the first fecal microbiota product, Rebyota, to prevent recurrence of C. difficile. More recently, in April 2023, the FDA approved Vowst, a pill for treating recurrent C. difficile infections.

Dr. Kelly also noted that the article by Dr. Yadegar and colleagues “may help us understand why a small percentage of patients fail to achieve cure after FMT.”

Regarding Dr. Porcari and colleagues’ article, Dr. Kelly said, “There is a lot of hope that FMT or other gut microbiome therapies will be beneficial for conditions outside of C. difficile.

“They do a good job reviewing the state of the science of FMT and highlight the many unknowns around the use of FMT in conditions outside of C. difficile,” added Dr. Kelly, who has been using FMT to treat C. difficile for more than 15 years.

Data supporting FMT for conditions such as ulcerative colitis and autism are compelling, Dr. Kelly acknowledged. But in her view, FMT isn’t ready for “prime time” outside of C. difficile – at least not yet.

“Academic investigators and those in industry are actively conducting research in many non–C. difficile indications, and I predict we will see the emergence of gut microbiome–based therapies for other indications within the next 5-10 years,” Dr. Kelly said.

Dr. Yadegar reports no relevant financial relationships. One coauthor of the Yadegar study has served on the adjudication board for Finch Therapeutics and has received consulting fees and a speaking honorarium from Rebiotix/Ferring Pharmaceuticals. Dr. Ianiro reports no relevant financial relationships. Dr. Kelly has consulted for Sebela Pharmaceuticals and is one of the principal investigators for the FMT National Patient Registry funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

A version of this article originally appeared on Medscape.com.

A deeper understanding of the mechanisms underlying the success of fecal microbiota transplantation (FMT) is needed to further improve its effectiveness, according to two recent reviews published in Cell Host and Microbe.

Both research teams agree that more needs to be known about how various underexplored factors – such as the patient’s diet and genetic background, how closely the donor’s microbial composition matches the patient’s existing microbiome, and the presence of nonbacterial gut inhabitants like viruses and fungi – affect FMT success, according to a press release.

FMT is most often used to treat recurrent Clostridioides difficile infections, which don’t always respond to antibiotics. Success rates range from 60% to 90%, depending on the administration route and study design, notes an international research team led by Abbas Yadegar, PhD, a medical bacteriologist at the Shahid Beheshti University of Medical Sciences in Tehran, Iran.

The understanding of how FMT works is incomplete, however, and the reasons some patients fail to benefit is unclear, note Dr. Yadegar and colleagues. Little attention has been paid to the role that other components of the patient’s microbiome, along with outside factors, play in the treatment’s success, they add.

“We wanted other researchers to look beyond changes in stool microbial composition and function, which have been the focus of research in the past few years,” Dr. Yadegar’s team said in a statement provided to this news organization.

Dr. Yadegar and colleagues’ review of more than 130 studies summarizes recent evidence on the mechanisms contributing to FMT success against recurrent C. difficile infection, highlights knowledge gaps, and proposes future research directions in the field.

Factors that influence FMT’s effectiveness and the potential the procedure holds for treatment of other diseases associated with gut dysbiosis are the subject of a review of 149 studies by a team of researchers led by Serena Porcari, MD, a gastroenterologist at the Fondazione Policlinico Universitario Gemelli and Università Cattolica del Sacro Cuore, in Rome.

“Our main goal was not only to unravel the different mechanisms of FMT efficacy but also to introduce some mindset shifts that are needed to bring FMT forward, mainly covering the gap that exists between basic scientists and clinicians,” Gianluca Ianiro, MD, PhD, a senior researcher in digestive diseases who works with Dr. Porcari and is the review’s lead author, told this news organization.
 

Engraftment may influence success

Engraftment of donor microbial strains in recipients appears to be key to the therapeutic success of FMT, both reviews note.

Three factors influence engraftment: the donor’s bacteria fitness relative to the recipient, the bacteria already present in the recipient, and whether antibiotics are used prior to FMT to open a niche for the incoming donor microbes, according to Dr. Yadegar and colleagues.

How to calculate strain engraftment has not yet been standardized in the field, and the number of strains detected in the recipient’s fecal sample is dependent on the depth of sequencing techniques, Dr. Porcari and colleagues note.

The use of whole-genome sequencing has enabled more precise evaluation of engraftment, they add.

“With this approach, microbial engraftment has been associated with clinical success, regardless of the disease, in a large metagenomic metanalysis of 24 FMT trials and almost 1,400 fecal samples,” Dr. Porcari and colleagues write. However, these results have not been replicated, likely because of differences between the studies.

More study on the topic is needed, both articles note.

“Because the recent metagenomics studies compared pre- and post-FMT only in cases with successful treatment outcomes, it is not possible to link engraftment to clinical outcomes,” Dr. Yadegar and colleagues write in their statement to this news organization.
 

A closer look at donor-recipient pairings

Clinicians usually enlist healthy, carefully screened individuals as FMT donors.

However, both research groups conclude that fine-scale taxonomic and metabolic analyses of donor and recipient microbiomes would better inform clinical decisions, especially when treating diseases other than C. difficile.

This may call for a more personalized approach to choosing donor-recipient pairings. Investigators should assess the patient’s diet and genetic background and how closely the donor’s microbiome matches that of the patient.

“Most studies focused on profiling stool samples before and after FMT without also including functional analyses; therefore, there are still a lot of aspects of host microbial interactions that remain unknown,” write Dr. Yadegar and colleagues in their statement.

Ecologic factors, including diet and host genetics, are often not included in clinical studies of C. difficile, but they “may potentially be the missing links” to treatment failure in the small portion of patients whose condition doesn’t respond to FMT, they write.

Pairing donor-recipient combinations on the basis of dietary patterns and preferences could improve FMT efficacy because the donor microbiota would be preadapted to the recipient’s diet, Dr. Yadegar and colleagues write. The team is examining how donor and recipient diet may affect outcomes.

Dr. Porcari and colleagues add that while some studies support the existence of shared characteristics that make up super-donors, others found that the optimal donor is more patient specific. They call for personalized selection strategies that employ microbiome sequencing tools rather than a “one stool fits all” approach.

Currently, many clinicians aren’t familiar with microbiome sequencing and analysis, but they’ll need to be in the near future, note Dr. Porcari and colleagues.

“Identifying microbiome characteristics that maximize strain engraftment in the FMT will allow clinicians to select the best donor for each single patient,” they write.
 

The possible role of viruses and fungi

In FMT research, investigators tend to focus on the bacteria in the human microbiome. However, viruses and fungi also appear to play a role, both articles note.

“Other microbial kingdoms that inhabit the intestine should be taken into account when considering predictors of post-FMT microbial transfer,” write Dr. Porcari and colleagues.

Although few studies have examined the gut virome’s impact on FMT effectiveness against C. difficile, the existing research, although limited, indicates that bacteriophage viruses could play a role, Dr. Yadegar and colleagues note. For example, high levels of donor-derived Caudoviralesbacteriophages in recipients were associated with FMT efficacy in one preliminary study, they write.

In a small human study, fecal filtrate from healthy donors who had bacteriophages but no live bacteria successfully treated five patients with recurrent C. difficile infection, Dr. Yadegar and colleagues write.

“Therefore, the idea that viruses may play a role is very provocative,” write Dr. Yadegar’s team in their statement.

It’s important to note that these studies are associative, which means they can’t definitively answer the question of how or whether viruses play a role, Dr. Yadegar’s team added.

Researchers “know even less about how fungi may or may not play a role,” write Dr. Yadegar and colleagues. However, in early research that involved patients who had successfully undergone FMT for C. difficile, there was higher relative abundance of Saccharomyces and Aspergillus, whereas Candida, if prominent, may impede response, they write in their article.

Additionally, to explore whether live bacteria are necessary for FMT to work, Dr. Yadegar and colleagues informed this news organization that they are conducting a study “comparing traditional FMT to a fecal filtrate that contains no live bacteria, but has all other components, to see if we can achieve similar success rates in recurrent C. difficile infection.”
 

Repeat treatment for sustained response

Dr. Yadegar’s team offered another important takeaway: A single FMT treatment will not sustain a positive response, especially when treating chronic noncommunicable conditions in which intestinal dysbiosis may play a role. Repeat treatment will be needed, as with other chronic conditions. This has been shown even in C. difficile infection.

“Recent studies have documented a significant advantage of repeated FMT over single FMT on the cure rates of recurrent C. difficile,” especially for patients with inflammatory bowel disorder, Dr. Yadegar’s team told this news organization.

“What we don’t know is which patient is likely to respond to microbial-based therapy, or what the dose or frequency should be, or which bacteria are responsible for the effects,” Dr. Yadegar and team said.

Dr. Porcari and colleagues are examining whether FMT could be refined to improve its success against other diseases. This may involve selecting specific donors, monitoring the gut microbiome of both donors and recipients, or using a specific means of delivery, such as lyophilized capsules, Dr. Ianiro said.

A response to FMT for chronic, noncommunicable disorders typically is not sustained long term, note Dr. Porcari and colleagues. However, they add that “sequential transplants have been applied in this setting with promising results, suggesting that chronic modulation of the patient microbiome may be beneficial in noncommunicable chronic disorders.” Dr. Porcari and colleagues point to the success of repeated, long-term FMT in studies of patients with ulcerative colitis and irritable bowel syndrome.

The use of cutting-edge technologies for microbiome assessment and a change in the view of FMT as only an acute, single-use therapy could improve FMT protocols and outcomes for noncommunicable conditions, they write.
 

Expanding FMT beyond C. difficile

Dr. Yadegar and colleagues’ article “really breaks down what is known about the mechanisms of FMT in C. difficile infection, which is important as other live biotherapeutic products are developed,” Colleen Kelly, MD, an associate professor of medicine at Brown University in Providence, R.I., who was not involved with the reviews, said in an interview.

Dr. Yadegar and colleagues concur. They note in a press release that as the mechanisms behind FMT success are understood, that information should be used to design new standardized therapies.

“Although highly effective, there are substantial drawbacks with [FMT], including infectious risks and sparse long-term safety data,” they write. “Better treatment options for recurrent C. difficile infections that are targeted, safe, and donor-independent are thus desired.”

In December 2022, the U.S. Food and Drug Administration approved the first fecal microbiota product, Rebyota, to prevent recurrence of C. difficile. More recently, in April 2023, the FDA approved Vowst, a pill for treating recurrent C. difficile infections.

Dr. Kelly also noted that the article by Dr. Yadegar and colleagues “may help us understand why a small percentage of patients fail to achieve cure after FMT.”

Regarding Dr. Porcari and colleagues’ article, Dr. Kelly said, “There is a lot of hope that FMT or other gut microbiome therapies will be beneficial for conditions outside of C. difficile.

“They do a good job reviewing the state of the science of FMT and highlight the many unknowns around the use of FMT in conditions outside of C. difficile,” added Dr. Kelly, who has been using FMT to treat C. difficile for more than 15 years.

Data supporting FMT for conditions such as ulcerative colitis and autism are compelling, Dr. Kelly acknowledged. But in her view, FMT isn’t ready for “prime time” outside of C. difficile – at least not yet.

“Academic investigators and those in industry are actively conducting research in many non–C. difficile indications, and I predict we will see the emergence of gut microbiome–based therapies for other indications within the next 5-10 years,” Dr. Kelly said.

Dr. Yadegar reports no relevant financial relationships. One coauthor of the Yadegar study has served on the adjudication board for Finch Therapeutics and has received consulting fees and a speaking honorarium from Rebiotix/Ferring Pharmaceuticals. Dr. Ianiro reports no relevant financial relationships. Dr. Kelly has consulted for Sebela Pharmaceuticals and is one of the principal investigators for the FMT National Patient Registry funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

A version of this article originally appeared on Medscape.com.

A deeper understanding of the mechanisms underlying the success of fecal microbiota transplantation (FMT) is needed to further improve its effectiveness, according to two recent reviews published in Cell Host and Microbe.

Both research teams agree that more needs to be known about how various underexplored factors – such as the patient’s diet and genetic background, how closely the donor’s microbial composition matches the patient’s existing microbiome, and the presence of nonbacterial gut inhabitants like viruses and fungi – affect FMT success, according to a press release.

FMT is most often used to treat recurrent Clostridioides difficile infections, which don’t always respond to antibiotics. Success rates range from 60% to 90%, depending on the administration route and study design, notes an international research team led by Abbas Yadegar, PhD, a medical bacteriologist at the Shahid Beheshti University of Medical Sciences in Tehran, Iran.

The understanding of how FMT works is incomplete, however, and the reasons some patients fail to benefit is unclear, note Dr. Yadegar and colleagues. Little attention has been paid to the role that other components of the patient’s microbiome, along with outside factors, play in the treatment’s success, they add.

“We wanted other researchers to look beyond changes in stool microbial composition and function, which have been the focus of research in the past few years,” Dr. Yadegar’s team said in a statement provided to this news organization.

Dr. Yadegar and colleagues’ review of more than 130 studies summarizes recent evidence on the mechanisms contributing to FMT success against recurrent C. difficile infection, highlights knowledge gaps, and proposes future research directions in the field.

Factors that influence FMT’s effectiveness and the potential the procedure holds for treatment of other diseases associated with gut dysbiosis are the subject of a review of 149 studies by a team of researchers led by Serena Porcari, MD, a gastroenterologist at the Fondazione Policlinico Universitario Gemelli and Università Cattolica del Sacro Cuore, in Rome.

“Our main goal was not only to unravel the different mechanisms of FMT efficacy but also to introduce some mindset shifts that are needed to bring FMT forward, mainly covering the gap that exists between basic scientists and clinicians,” Gianluca Ianiro, MD, PhD, a senior researcher in digestive diseases who works with Dr. Porcari and is the review’s lead author, told this news organization.
 

Engraftment may influence success

Engraftment of donor microbial strains in recipients appears to be key to the therapeutic success of FMT, both reviews note.

Three factors influence engraftment: the donor’s bacteria fitness relative to the recipient, the bacteria already present in the recipient, and whether antibiotics are used prior to FMT to open a niche for the incoming donor microbes, according to Dr. Yadegar and colleagues.

How to calculate strain engraftment has not yet been standardized in the field, and the number of strains detected in the recipient’s fecal sample is dependent on the depth of sequencing techniques, Dr. Porcari and colleagues note.

The use of whole-genome sequencing has enabled more precise evaluation of engraftment, they add.

“With this approach, microbial engraftment has been associated with clinical success, regardless of the disease, in a large metagenomic metanalysis of 24 FMT trials and almost 1,400 fecal samples,” Dr. Porcari and colleagues write. However, these results have not been replicated, likely because of differences between the studies.

More study on the topic is needed, both articles note.

“Because the recent metagenomics studies compared pre- and post-FMT only in cases with successful treatment outcomes, it is not possible to link engraftment to clinical outcomes,” Dr. Yadegar and colleagues write in their statement to this news organization.
 

A closer look at donor-recipient pairings

Clinicians usually enlist healthy, carefully screened individuals as FMT donors.

However, both research groups conclude that fine-scale taxonomic and metabolic analyses of donor and recipient microbiomes would better inform clinical decisions, especially when treating diseases other than C. difficile.

This may call for a more personalized approach to choosing donor-recipient pairings. Investigators should assess the patient’s diet and genetic background and how closely the donor’s microbiome matches that of the patient.

“Most studies focused on profiling stool samples before and after FMT without also including functional analyses; therefore, there are still a lot of aspects of host microbial interactions that remain unknown,” write Dr. Yadegar and colleagues in their statement.

Ecologic factors, including diet and host genetics, are often not included in clinical studies of C. difficile, but they “may potentially be the missing links” to treatment failure in the small portion of patients whose condition doesn’t respond to FMT, they write.

Pairing donor-recipient combinations on the basis of dietary patterns and preferences could improve FMT efficacy because the donor microbiota would be preadapted to the recipient’s diet, Dr. Yadegar and colleagues write. The team is examining how donor and recipient diet may affect outcomes.

Dr. Porcari and colleagues add that while some studies support the existence of shared characteristics that make up super-donors, others found that the optimal donor is more patient specific. They call for personalized selection strategies that employ microbiome sequencing tools rather than a “one stool fits all” approach.

Currently, many clinicians aren’t familiar with microbiome sequencing and analysis, but they’ll need to be in the near future, note Dr. Porcari and colleagues.

“Identifying microbiome characteristics that maximize strain engraftment in the FMT will allow clinicians to select the best donor for each single patient,” they write.
 

The possible role of viruses and fungi

In FMT research, investigators tend to focus on the bacteria in the human microbiome. However, viruses and fungi also appear to play a role, both articles note.

“Other microbial kingdoms that inhabit the intestine should be taken into account when considering predictors of post-FMT microbial transfer,” write Dr. Porcari and colleagues.

Although few studies have examined the gut virome’s impact on FMT effectiveness against C. difficile, the existing research, although limited, indicates that bacteriophage viruses could play a role, Dr. Yadegar and colleagues note. For example, high levels of donor-derived Caudoviralesbacteriophages in recipients were associated with FMT efficacy in one preliminary study, they write.

In a small human study, fecal filtrate from healthy donors who had bacteriophages but no live bacteria successfully treated five patients with recurrent C. difficile infection, Dr. Yadegar and colleagues write.

“Therefore, the idea that viruses may play a role is very provocative,” write Dr. Yadegar’s team in their statement.

It’s important to note that these studies are associative, which means they can’t definitively answer the question of how or whether viruses play a role, Dr. Yadegar’s team added.

Researchers “know even less about how fungi may or may not play a role,” write Dr. Yadegar and colleagues. However, in early research that involved patients who had successfully undergone FMT for C. difficile, there was higher relative abundance of Saccharomyces and Aspergillus, whereas Candida, if prominent, may impede response, they write in their article.

Additionally, to explore whether live bacteria are necessary for FMT to work, Dr. Yadegar and colleagues informed this news organization that they are conducting a study “comparing traditional FMT to a fecal filtrate that contains no live bacteria, but has all other components, to see if we can achieve similar success rates in recurrent C. difficile infection.”
 

Repeat treatment for sustained response

Dr. Yadegar’s team offered another important takeaway: A single FMT treatment will not sustain a positive response, especially when treating chronic noncommunicable conditions in which intestinal dysbiosis may play a role. Repeat treatment will be needed, as with other chronic conditions. This has been shown even in C. difficile infection.

“Recent studies have documented a significant advantage of repeated FMT over single FMT on the cure rates of recurrent C. difficile,” especially for patients with inflammatory bowel disorder, Dr. Yadegar’s team told this news organization.

“What we don’t know is which patient is likely to respond to microbial-based therapy, or what the dose or frequency should be, or which bacteria are responsible for the effects,” Dr. Yadegar and team said.

Dr. Porcari and colleagues are examining whether FMT could be refined to improve its success against other diseases. This may involve selecting specific donors, monitoring the gut microbiome of both donors and recipients, or using a specific means of delivery, such as lyophilized capsules, Dr. Ianiro said.

A response to FMT for chronic, noncommunicable disorders typically is not sustained long term, note Dr. Porcari and colleagues. However, they add that “sequential transplants have been applied in this setting with promising results, suggesting that chronic modulation of the patient microbiome may be beneficial in noncommunicable chronic disorders.” Dr. Porcari and colleagues point to the success of repeated, long-term FMT in studies of patients with ulcerative colitis and irritable bowel syndrome.

The use of cutting-edge technologies for microbiome assessment and a change in the view of FMT as only an acute, single-use therapy could improve FMT protocols and outcomes for noncommunicable conditions, they write.
 

Expanding FMT beyond C. difficile

Dr. Yadegar and colleagues’ article “really breaks down what is known about the mechanisms of FMT in C. difficile infection, which is important as other live biotherapeutic products are developed,” Colleen Kelly, MD, an associate professor of medicine at Brown University in Providence, R.I., who was not involved with the reviews, said in an interview.

Dr. Yadegar and colleagues concur. They note in a press release that as the mechanisms behind FMT success are understood, that information should be used to design new standardized therapies.

“Although highly effective, there are substantial drawbacks with [FMT], including infectious risks and sparse long-term safety data,” they write. “Better treatment options for recurrent C. difficile infections that are targeted, safe, and donor-independent are thus desired.”

In December 2022, the U.S. Food and Drug Administration approved the first fecal microbiota product, Rebyota, to prevent recurrence of C. difficile. More recently, in April 2023, the FDA approved Vowst, a pill for treating recurrent C. difficile infections.

Dr. Kelly also noted that the article by Dr. Yadegar and colleagues “may help us understand why a small percentage of patients fail to achieve cure after FMT.”

Regarding Dr. Porcari and colleagues’ article, Dr. Kelly said, “There is a lot of hope that FMT or other gut microbiome therapies will be beneficial for conditions outside of C. difficile.

“They do a good job reviewing the state of the science of FMT and highlight the many unknowns around the use of FMT in conditions outside of C. difficile,” added Dr. Kelly, who has been using FMT to treat C. difficile for more than 15 years.

Data supporting FMT for conditions such as ulcerative colitis and autism are compelling, Dr. Kelly acknowledged. But in her view, FMT isn’t ready for “prime time” outside of C. difficile – at least not yet.

“Academic investigators and those in industry are actively conducting research in many non–C. difficile indications, and I predict we will see the emergence of gut microbiome–based therapies for other indications within the next 5-10 years,” Dr. Kelly said.

Dr. Yadegar reports no relevant financial relationships. One coauthor of the Yadegar study has served on the adjudication board for Finch Therapeutics and has received consulting fees and a speaking honorarium from Rebiotix/Ferring Pharmaceuticals. Dr. Ianiro reports no relevant financial relationships. Dr. Kelly has consulted for Sebela Pharmaceuticals and is one of the principal investigators for the FMT National Patient Registry funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

A version of this article originally appeared on Medscape.com.

Around 50% of patients develop an infection in the final months, weeks, or days before their deaths. Diagnosing an infection is complex because of the presence of symptoms that are often nonspecific and that are common in patients in decline toward the end of life. Use of antibiotic therapy in this patient population is still controversial, because the clinical benefits are not clear and the risk of pointless overmedicalization is very high.

Etiology

For patients who are receiving palliative care, the following factors predispose to an infection:

• Increasing fragility.
• Bedbound status and anorexia/cachexia syndrome.
• Weakened immune defenses owing to disease or treatments.
• Changes to skin integrity, related to venous access sites and/or bladder catheterization.

Four-week cutoff

For patients who are expected to live for fewer than 4 weeks, evidence from the literature shows that antimicrobial therapy does not resolve a potential infection or improve the prognosis. Antibiotics should therefore be used only for improving symptom management.

In practice, the most common infections in patients receiving end-of-life care are in the urinary and respiratory tracts. Antibiotics are beneficial in the short term in managing symptoms associated with urinary tract infections (effective in 60%-92% of cases), so they should be considered if the patient is not in the agonal or pre-agonal phase of death.

Antibiotics are also beneficial in managing symptoms associated with respiratory tract infections (effective in up to 53% of cases), so they should be considered if the patient is not in the agonal or pre-agonal phase of death. However, the risk of futility is high. As an alternative, opioids and antitussives could provide greater benefit for patients with dyspnea and cough.

No benefit has been observed with the use of antibiotics to treat symptoms associated with sepsis, abscesses, and deep and complicated infections. Antibiotics are therefore deemed futile in these cases.

In unclear cases, the “2-day rule” is useful. This involves waiting for 2 days, and if the patient remains clinically stable, prescribing antibiotics. If the patient’s condition deteriorates rapidly and progressively, antibiotics should not be prescribed.

Alternatively, one can prescribe antibiotics immediately. If no clinical improvement is observed after 2 days, the antibiotics should be stopped, especially if deterioration of the patient’s condition is rapid and progressive.

Increased body temperature is somewhat common in the last days and hours of life and is not generally associated with symptoms. Fever in these cases is not an indication for the use of antimicrobial therapy.

The most common laboratory markers of infection (C-reactive protein level, erythrocyte sedimentation rate, leukocyte level) are not particularly useful in this patient population, because they are affected by the baseline condition as well as by any treatments given and the state of systemic inflammation, which is associated with the decline in overall health in the last few weeks of life.

The choice should be individualized and shared with patients and family members so that the clinical appropriateness of the therapeutic strategy is evident and that decisions regarding antibiotic treatment are not regarded as a failure to treat the patient.
 

The longer term

In deciding to start antibiotic therapy, consideration must be given to the patient’s overall health, the treatment objectives, the possibility that the antibiotic will resolve the infection or improve the patient’s symptoms, and the estimated prognosis, which must be sufficiently long to allow the antibiotic time to take effect.

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

Around 50% of patients develop an infection in the final months, weeks, or days before their deaths. Diagnosing an infection is complex because of the presence of symptoms that are often nonspecific and that are common in patients in decline toward the end of life. Use of antibiotic therapy in this patient population is still controversial, because the clinical benefits are not clear and the risk of pointless overmedicalization is very high.

Etiology

For patients who are receiving palliative care, the following factors predispose to an infection:

• Increasing fragility.
• Bedbound status and anorexia/cachexia syndrome.
• Weakened immune defenses owing to disease or treatments.
• Changes to skin integrity, related to venous access sites and/or bladder catheterization.

Four-week cutoff

For patients who are expected to live for fewer than 4 weeks, evidence from the literature shows that antimicrobial therapy does not resolve a potential infection or improve the prognosis. Antibiotics should therefore be used only for improving symptom management.

In practice, the most common infections in patients receiving end-of-life care are in the urinary and respiratory tracts. Antibiotics are beneficial in the short term in managing symptoms associated with urinary tract infections (effective in 60%-92% of cases), so they should be considered if the patient is not in the agonal or pre-agonal phase of death.

Antibiotics are also beneficial in managing symptoms associated with respiratory tract infections (effective in up to 53% of cases), so they should be considered if the patient is not in the agonal or pre-agonal phase of death. However, the risk of futility is high. As an alternative, opioids and antitussives could provide greater benefit for patients with dyspnea and cough.

No benefit has been observed with the use of antibiotics to treat symptoms associated with sepsis, abscesses, and deep and complicated infections. Antibiotics are therefore deemed futile in these cases.

In unclear cases, the “2-day rule” is useful. This involves waiting for 2 days, and if the patient remains clinically stable, prescribing antibiotics. If the patient’s condition deteriorates rapidly and progressively, antibiotics should not be prescribed.

Alternatively, one can prescribe antibiotics immediately. If no clinical improvement is observed after 2 days, the antibiotics should be stopped, especially if deterioration of the patient’s condition is rapid and progressive.

Increased body temperature is somewhat common in the last days and hours of life and is not generally associated with symptoms. Fever in these cases is not an indication for the use of antimicrobial therapy.

The most common laboratory markers of infection (C-reactive protein level, erythrocyte sedimentation rate, leukocyte level) are not particularly useful in this patient population, because they are affected by the baseline condition as well as by any treatments given and the state of systemic inflammation, which is associated with the decline in overall health in the last few weeks of life.

The choice should be individualized and shared with patients and family members so that the clinical appropriateness of the therapeutic strategy is evident and that decisions regarding antibiotic treatment are not regarded as a failure to treat the patient.
 

The longer term

In deciding to start antibiotic therapy, consideration must be given to the patient’s overall health, the treatment objectives, the possibility that the antibiotic will resolve the infection or improve the patient’s symptoms, and the estimated prognosis, which must be sufficiently long to allow the antibiotic time to take effect.

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

Around 50% of patients develop an infection in the final months, weeks, or days before their deaths. Diagnosing an infection is complex because of the presence of symptoms that are often nonspecific and that are common in patients in decline toward the end of life. Use of antibiotic therapy in this patient population is still controversial, because the clinical benefits are not clear and the risk of pointless overmedicalization is very high.

Etiology

For patients who are receiving palliative care, the following factors predispose to an infection:

• Increasing fragility.
• Bedbound status and anorexia/cachexia syndrome.
• Weakened immune defenses owing to disease or treatments.
• Changes to skin integrity, related to venous access sites and/or bladder catheterization.

Four-week cutoff

For patients who are expected to live for fewer than 4 weeks, evidence from the literature shows that antimicrobial therapy does not resolve a potential infection or improve the prognosis. Antibiotics should therefore be used only for improving symptom management.

In practice, the most common infections in patients receiving end-of-life care are in the urinary and respiratory tracts. Antibiotics are beneficial in the short term in managing symptoms associated with urinary tract infections (effective in 60%-92% of cases), so they should be considered if the patient is not in the agonal or pre-agonal phase of death.

Antibiotics are also beneficial in managing symptoms associated with respiratory tract infections (effective in up to 53% of cases), so they should be considered if the patient is not in the agonal or pre-agonal phase of death. However, the risk of futility is high. As an alternative, opioids and antitussives could provide greater benefit for patients with dyspnea and cough.

No benefit has been observed with the use of antibiotics to treat symptoms associated with sepsis, abscesses, and deep and complicated infections. Antibiotics are therefore deemed futile in these cases.

In unclear cases, the “2-day rule” is useful. This involves waiting for 2 days, and if the patient remains clinically stable, prescribing antibiotics. If the patient’s condition deteriorates rapidly and progressively, antibiotics should not be prescribed.

Alternatively, one can prescribe antibiotics immediately. If no clinical improvement is observed after 2 days, the antibiotics should be stopped, especially if deterioration of the patient’s condition is rapid and progressive.

Increased body temperature is somewhat common in the last days and hours of life and is not generally associated with symptoms. Fever in these cases is not an indication for the use of antimicrobial therapy.

The most common laboratory markers of infection (C-reactive protein level, erythrocyte sedimentation rate, leukocyte level) are not particularly useful in this patient population, because they are affected by the baseline condition as well as by any treatments given and the state of systemic inflammation, which is associated with the decline in overall health in the last few weeks of life.

The choice should be individualized and shared with patients and family members so that the clinical appropriateness of the therapeutic strategy is evident and that decisions regarding antibiotic treatment are not regarded as a failure to treat the patient.
 

The longer term

In deciding to start antibiotic therapy, consideration must be given to the patient’s overall health, the treatment objectives, the possibility that the antibiotic will resolve the infection or improve the patient’s symptoms, and the estimated prognosis, which must be sufficiently long to allow the antibiotic time to take effect.

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

Sowing the seeds of cancer prevention

Are you looking to add to your quality of life, even though pets are not your speed? Might we suggest something with lower maintenance? Something a little greener?

Indoor plants can purify the air that comes from outside. Researchers at the University of Technology Sydney, in partnership with the plantscaping company Ambius, showed that a “green wall” made up of mixed indoor plants was able to suck up 97% of “the most toxic compounds” from the air in just 8 hours. We’re talking about lung-irritating, headache-inducing, cancer risk–boosting compounds from gasoline fumes, including benzene.

Fraser Torpy/University of Technology Sydney

Public health initiatives often strive to reduce cardiovascular and obesity risks, but breathing seems pretty important too. According to the World Health Organization, household air pollution is responsible for about 2.5 million global premature deaths each year. And since 2020 we’ve become accustomed to spending more time inside and at home.

“This new research proves that plants should not just be seen as ‘nice to have,’ but rather a crucial part of every workplace wellness plan,” Ambius General Manager Johan Hodgson said in statement released by the university.

So don’t spend hundreds of dollars on a fancy air filtration system when a wall of plants can do that for next to nothing. Find what works for you and your space and become a plant parent today! Your lungs will thank you.
 

But officer, I had to swerve to miss the duodenal ampulla

Tiny video capsule endoscopes have been around for many years, but they have one big weakness: The ingestible cameras’ journey through the GI tract is passively driven by gravity and the natural movement of the body, so they often miss potential problem areas.

AnX Robotica

Not anymore. That flaw has been addressed by medical technology company AnX Robotica, which has taken endoscopy to the next level by adding that wondrous directional control device of the modern electronic age, a joystick.

The new system “uses an external magnet and hand-held video game style joysticks to move the capsule in three dimensions,” which allows physicians to “remotely drive a miniature video capsule to all regions of the stomach to visualize and photograph potential problem areas,” according to Andrew C. Meltzer, MD, of George Washington University and associates, who conducted a pilot study funded by AnX Robotica.

The video capsule provided a 95% rate of visualization in the stomachs of 40 patients who were examined at a medical office building by an emergency medicine physician who had no previous specialty training in endoscopy. “Capsules were driven by the ER physician and then the study reports were reviewed by an attending gastroenterologist who was physically off site,” the investigators said in a written statement.

The capsule operator did receive some additional training, and development of artificial intelligence to self-drive the capsule is in the works, but for now, we’re talking about a device controlled by a human using a joystick. And we all know that 50-year-olds are not especially known for their joystick skills. For that we need real experts. Yup, we need to put those joystick-controlled capsule endoscopes in the hands of teenage gamers. Who wants to go first?
 

Maybe AI isn’t ready for the big time after all

“How long before some intrepid stockholder says: ‘Hey, instead of paying doctors, why don’t we just use the free robot instead?’ ” Those words appeared on LOTME but a month ago. After all, the AI is supposed to be smarter and more empathetic than a doctor. And did we mention it’s free? Or at least extremely cheap. Cheaper than, say, a group of recently unionized health care workers.

maewjpho/Thinkstock

In early May, the paid employees manning the National Eating Disorders Association emergency hotline voted to unionize, as they felt overwhelmed and underpaid. Apparently, paying six people an extra few thousand a year was too much for NEDA’s leadership, as they decided a few weeks later to fire those workers, fully closing down the hotline. Instead of talking to a real person, people “calling in” for support would be met with Tessa, a wellness chatbot that would hopefully guide them through their crisis. Key word, hopefully.

In perhaps the least surprising twist of the year, NEDA was forced to walk back its decision about a week after its initial announcement. It all started with a viral Instagram post from a woman who called in and received the following advice from Tessa: Lose 1-2 pounds a week, count calories and work for a 500- to 1,000-calorie deficit, weigh herself weekly, and restrict her diet. Unfortunately, all of these suggestions were things that led to the development of the woman’s eating disorder.

Naturally, NEDA responded in good grace, accusing the woman of lying. A NEDA vice president even left some nasty comments on the post, but hastily deleted them a day later when NEDA announced it was shutting down Tessa “until further notice for a complete investigation.” NEDA’s CEO insisted they hadn’t seen that behavior from Tessa before, calling it a “bug” and insisting the bot would only be down temporarily until the triggers causing the bug were fixed.

In the aftermath, several doctors and psychologists chimed in, terming the rush to automate human roles dangerous and risky. After all, much of what makes these hotlines effective is the volunteers speaking from their own experience. An unsupervised bot doesn’t seem to have what it takes to deal with a mental health crisis, but we’re betting that Tessa will be back. As a wise cephalopod once said: Nobody gives a care about the fate of labor as long as they can get their instant gratification.
 

You can’t spell existential without s-t-e-n-t

This week, we’re including a special “bonus” item that, to be honest, has nothing to do with stents. That’s why our editor is making us call this a “bonus” (and making us use quote marks, too): It doesn’t really have anything to do with stents or health care or those who practice health care. Actually, his exact words were, “You can’t just give the readers someone else’s ****ing list and expect to get paid for it.” Did we mention that he looks like Jack Nicklaus but acts like BoJack Horseman?

Anywaaay, we’re pretty sure that the list in question – “America’s Top 10 Most Googled Existential Questions” – says something about the human condition, just not about stents:

1. Why is the sky blue?

2. What do dreams mean?

3. What is the meaning of life?

4. Why am I so tired?

5. Who am I?

6. What is love?

7. Is a hot dog a sandwich?

8. What came first, the chicken or the egg?

9. What should I do?

10. Do animals have souls?

Sowing the seeds of cancer prevention

Are you looking to add to your quality of life, even though pets are not your speed? Might we suggest something with lower maintenance? Something a little greener?

Indoor plants can purify the air that comes from outside. Researchers at the University of Technology Sydney, in partnership with the plantscaping company Ambius, showed that a “green wall” made up of mixed indoor plants was able to suck up 97% of “the most toxic compounds” from the air in just 8 hours. We’re talking about lung-irritating, headache-inducing, cancer risk–boosting compounds from gasoline fumes, including benzene.

Fraser Torpy/University of Technology Sydney

Public health initiatives often strive to reduce cardiovascular and obesity risks, but breathing seems pretty important too. According to the World Health Organization, household air pollution is responsible for about 2.5 million global premature deaths each year. And since 2020 we’ve become accustomed to spending more time inside and at home.

“This new research proves that plants should not just be seen as ‘nice to have,’ but rather a crucial part of every workplace wellness plan,” Ambius General Manager Johan Hodgson said in statement released by the university.

So don’t spend hundreds of dollars on a fancy air filtration system when a wall of plants can do that for next to nothing. Find what works for you and your space and become a plant parent today! Your lungs will thank you.
 

But officer, I had to swerve to miss the duodenal ampulla

Tiny video capsule endoscopes have been around for many years, but they have one big weakness: The ingestible cameras’ journey through the GI tract is passively driven by gravity and the natural movement of the body, so they often miss potential problem areas.

AnX Robotica

Not anymore. That flaw has been addressed by medical technology company AnX Robotica, which has taken endoscopy to the next level by adding that wondrous directional control device of the modern electronic age, a joystick.

The new system “uses an external magnet and hand-held video game style joysticks to move the capsule in three dimensions,” which allows physicians to “remotely drive a miniature video capsule to all regions of the stomach to visualize and photograph potential problem areas,” according to Andrew C. Meltzer, MD, of George Washington University and associates, who conducted a pilot study funded by AnX Robotica.

The video capsule provided a 95% rate of visualization in the stomachs of 40 patients who were examined at a medical office building by an emergency medicine physician who had no previous specialty training in endoscopy. “Capsules were driven by the ER physician and then the study reports were reviewed by an attending gastroenterologist who was physically off site,” the investigators said in a written statement.

The capsule operator did receive some additional training, and development of artificial intelligence to self-drive the capsule is in the works, but for now, we’re talking about a device controlled by a human using a joystick. And we all know that 50-year-olds are not especially known for their joystick skills. For that we need real experts. Yup, we need to put those joystick-controlled capsule endoscopes in the hands of teenage gamers. Who wants to go first?
 

Maybe AI isn’t ready for the big time after all

“How long before some intrepid stockholder says: ‘Hey, instead of paying doctors, why don’t we just use the free robot instead?’ ” Those words appeared on LOTME but a month ago. After all, the AI is supposed to be smarter and more empathetic than a doctor. And did we mention it’s free? Or at least extremely cheap. Cheaper than, say, a group of recently unionized health care workers.

maewjpho/Thinkstock

In early May, the paid employees manning the National Eating Disorders Association emergency hotline voted to unionize, as they felt overwhelmed and underpaid. Apparently, paying six people an extra few thousand a year was too much for NEDA’s leadership, as they decided a few weeks later to fire those workers, fully closing down the hotline. Instead of talking to a real person, people “calling in” for support would be met with Tessa, a wellness chatbot that would hopefully guide them through their crisis. Key word, hopefully.

In perhaps the least surprising twist of the year, NEDA was forced to walk back its decision about a week after its initial announcement. It all started with a viral Instagram post from a woman who called in and received the following advice from Tessa: Lose 1-2 pounds a week, count calories and work for a 500- to 1,000-calorie deficit, weigh herself weekly, and restrict her diet. Unfortunately, all of these suggestions were things that led to the development of the woman’s eating disorder.

Naturally, NEDA responded in good grace, accusing the woman of lying. A NEDA vice president even left some nasty comments on the post, but hastily deleted them a day later when NEDA announced it was shutting down Tessa “until further notice for a complete investigation.” NEDA’s CEO insisted they hadn’t seen that behavior from Tessa before, calling it a “bug” and insisting the bot would only be down temporarily until the triggers causing the bug were fixed.

In the aftermath, several doctors and psychologists chimed in, terming the rush to automate human roles dangerous and risky. After all, much of what makes these hotlines effective is the volunteers speaking from their own experience. An unsupervised bot doesn’t seem to have what it takes to deal with a mental health crisis, but we’re betting that Tessa will be back. As a wise cephalopod once said: Nobody gives a care about the fate of labor as long as they can get their instant gratification.
 

You can’t spell existential without s-t-e-n-t

This week, we’re including a special “bonus” item that, to be honest, has nothing to do with stents. That’s why our editor is making us call this a “bonus” (and making us use quote marks, too): It doesn’t really have anything to do with stents or health care or those who practice health care. Actually, his exact words were, “You can’t just give the readers someone else’s ****ing list and expect to get paid for it.” Did we mention that he looks like Jack Nicklaus but acts like BoJack Horseman?

Anywaaay, we’re pretty sure that the list in question – “America’s Top 10 Most Googled Existential Questions” – says something about the human condition, just not about stents:

1. Why is the sky blue?

2. What do dreams mean?

3. What is the meaning of life?

4. Why am I so tired?

5. Who am I?

6. What is love?

7. Is a hot dog a sandwich?

8. What came first, the chicken or the egg?

9. What should I do?

10. Do animals have souls?

Sowing the seeds of cancer prevention

Are you looking to add to your quality of life, even though pets are not your speed? Might we suggest something with lower maintenance? Something a little greener?

Indoor plants can purify the air that comes from outside. Researchers at the University of Technology Sydney, in partnership with the plantscaping company Ambius, showed that a “green wall” made up of mixed indoor plants was able to suck up 97% of “the most toxic compounds” from the air in just 8 hours. We’re talking about lung-irritating, headache-inducing, cancer risk–boosting compounds from gasoline fumes, including benzene.

Fraser Torpy/University of Technology Sydney

Public health initiatives often strive to reduce cardiovascular and obesity risks, but breathing seems pretty important too. According to the World Health Organization, household air pollution is responsible for about 2.5 million global premature deaths each year. And since 2020 we’ve become accustomed to spending more time inside and at home.

“This new research proves that plants should not just be seen as ‘nice to have,’ but rather a crucial part of every workplace wellness plan,” Ambius General Manager Johan Hodgson said in statement released by the university.

So don’t spend hundreds of dollars on a fancy air filtration system when a wall of plants can do that for next to nothing. Find what works for you and your space and become a plant parent today! Your lungs will thank you.
 

But officer, I had to swerve to miss the duodenal ampulla

Tiny video capsule endoscopes have been around for many years, but they have one big weakness: The ingestible cameras’ journey through the GI tract is passively driven by gravity and the natural movement of the body, so they often miss potential problem areas.

AnX Robotica

Not anymore. That flaw has been addressed by medical technology company AnX Robotica, which has taken endoscopy to the next level by adding that wondrous directional control device of the modern electronic age, a joystick.

The new system “uses an external magnet and hand-held video game style joysticks to move the capsule in three dimensions,” which allows physicians to “remotely drive a miniature video capsule to all regions of the stomach to visualize and photograph potential problem areas,” according to Andrew C. Meltzer, MD, of George Washington University and associates, who conducted a pilot study funded by AnX Robotica.

The video capsule provided a 95% rate of visualization in the stomachs of 40 patients who were examined at a medical office building by an emergency medicine physician who had no previous specialty training in endoscopy. “Capsules were driven by the ER physician and then the study reports were reviewed by an attending gastroenterologist who was physically off site,” the investigators said in a written statement.

The capsule operator did receive some additional training, and development of artificial intelligence to self-drive the capsule is in the works, but for now, we’re talking about a device controlled by a human using a joystick. And we all know that 50-year-olds are not especially known for their joystick skills. For that we need real experts. Yup, we need to put those joystick-controlled capsule endoscopes in the hands of teenage gamers. Who wants to go first?
 

Maybe AI isn’t ready for the big time after all

“How long before some intrepid stockholder says: ‘Hey, instead of paying doctors, why don’t we just use the free robot instead?’ ” Those words appeared on LOTME but a month ago. After all, the AI is supposed to be smarter and more empathetic than a doctor. And did we mention it’s free? Or at least extremely cheap. Cheaper than, say, a group of recently unionized health care workers.

maewjpho/Thinkstock

In early May, the paid employees manning the National Eating Disorders Association emergency hotline voted to unionize, as they felt overwhelmed and underpaid. Apparently, paying six people an extra few thousand a year was too much for NEDA’s leadership, as they decided a few weeks later to fire those workers, fully closing down the hotline. Instead of talking to a real person, people “calling in” for support would be met with Tessa, a wellness chatbot that would hopefully guide them through their crisis. Key word, hopefully.

In perhaps the least surprising twist of the year, NEDA was forced to walk back its decision about a week after its initial announcement. It all started with a viral Instagram post from a woman who called in and received the following advice from Tessa: Lose 1-2 pounds a week, count calories and work for a 500- to 1,000-calorie deficit, weigh herself weekly, and restrict her diet. Unfortunately, all of these suggestions were things that led to the development of the woman’s eating disorder.

Naturally, NEDA responded in good grace, accusing the woman of lying. A NEDA vice president even left some nasty comments on the post, but hastily deleted them a day later when NEDA announced it was shutting down Tessa “until further notice for a complete investigation.” NEDA’s CEO insisted they hadn’t seen that behavior from Tessa before, calling it a “bug” and insisting the bot would only be down temporarily until the triggers causing the bug were fixed.

In the aftermath, several doctors and psychologists chimed in, terming the rush to automate human roles dangerous and risky. After all, much of what makes these hotlines effective is the volunteers speaking from their own experience. An unsupervised bot doesn’t seem to have what it takes to deal with a mental health crisis, but we’re betting that Tessa will be back. As a wise cephalopod once said: Nobody gives a care about the fate of labor as long as they can get their instant gratification.
 

You can’t spell existential without s-t-e-n-t

This week, we’re including a special “bonus” item that, to be honest, has nothing to do with stents. That’s why our editor is making us call this a “bonus” (and making us use quote marks, too): It doesn’t really have anything to do with stents or health care or those who practice health care. Actually, his exact words were, “You can’t just give the readers someone else’s ****ing list and expect to get paid for it.” Did we mention that he looks like Jack Nicklaus but acts like BoJack Horseman?

Anywaaay, we’re pretty sure that the list in question – “America’s Top 10 Most Googled Existential Questions” – says something about the human condition, just not about stents:

1. Why is the sky blue?

2. What do dreams mean?

3. What is the meaning of life?

4. Why am I so tired?

5. Who am I?

6. What is love?

7. Is a hot dog a sandwich?

8. What came first, the chicken or the egg?

9. What should I do?

10. Do animals have souls?

To the Editor:

Dermatology is one of the most competitive residencies for matching, with a 57.5% match rate in 2022.¹ Our prior study of research-mentor relationships among matched dermatology applicants corroborated the importance of home programs (HPs) and program connections.² Therefore, our current objective was to compare profiles of matched dermatology applicants without HPs vs those with HPs.

We searched websites of 139 dermatology programs nationwide and found 1736 matched applicants from 2016 to 2020; of them, 323 did not have HPs. We determined program rank by research output using Doximity Residency Navigator (https://www.doximity.com/residency/). Advanced degrees (ADs) of applicants were identified using program websites and LinkedIn. A PubMed search was conducted for number of articles published by each applicant before September 15 of their match year. For applicants without HPs, we identified the senior author on each publication. The senior author publishing with an applicant most often was considered the research mentor. Two-tailed independent t tests and χ² tests were used to determine statistical significance (P<.05).

On average, matched applicants without HPs matched in lower-ranked (74.4) and smaller (12.4) programs compared with matched applicants with HPs (45.3 [P<.0001] and 15.1 [P<.0001], respectively)(eTable). The mean number of publications was similar between matched applicants with HPs and without HPs (5.64 and 4.80, respectively; P=.0525) as well as the percentage with ADs (14.7% and 11.5%, respectively; P=.0953). Overall, 14.8% of matched applicants without HPs matched at their mentors’ institutions.

Data were obtained for matched international applicants as a subset of non-HP applicants. Despite attending medical schools without associated HPs in the United States, international applicants matched at similarly ranked (44.3) and sized (15.0) programs, on average, compared with HP applicants. The mean number of publications was higher for international applicants (11.4) vs domestic applicants (5.33). International applicants more often had ADs (23.8%) and 60.1% of them held doctor of philosophy degrees. Overall, 40.5% of international applicants matched at their mentors’ institutions.

Our study suggests that matched dermatology applicants with and without HPs had similar achievements, on average, for the number of publications and percentage with ADs. However, non-HP applicants matched at lower-ranked programs than HP applicants. Therefore, applicants without HPs should strongly consider cultivating program connections, especially if they desire to match at higher-ranked dermatology programs. To illustrate, the rate of matching at research mentors’ institutions was approximately 3-times higher for international applicants than non-HP applicants overall. Despite the disadvantages of applying as international applicants, they were able to match at substantially higher-ranked dermatology programs than non-HP applicants. International applicants may have a longer time investment—the number of years from obtaining their medical degree or US medical license to matching—giving them time to produce quality research and develop meaningful relationships at an institution. Additionally, our prior study of the top 25 dermatology residencies showed that 26.2% of successful applicants matched at their research mentors’ institutions, with almost half of this subset matching at their HPs, where their mentors also practiced.² Because of the potential benefits of having program connections, applicants without HPs should seek dermatology research mentors, especially via highly beneficial in-person networking opportunities (eg, away rotations, conferences) that had previously been limited during the COVID-19 pandemic.³ Formal mentorship programs giving priority to students without HPs recently have been developed, which only begins to address the inequities in the dermatology residency application process.⁴

Study limitations include lack of resident information on 15 program websites, missed publications due to applicant name changes, not accounting for abstracts and posters, and inability to collect data on unmatched applicants.

We hope that our study alleviates some concerns that applicants without HPs may have regarding applying for dermatology residency and encourages those with a genuine interest in dermatology to pursue the specialty, provided they find a strong research mentor. Residency programs should be cognizant of the unique challenges that non-HP applicants face for matching.

To the Editor:

Dermatology is one of the most competitive residencies for matching, with a 57.5% match rate in 2022.¹ Our prior study of research-mentor relationships among matched dermatology applicants corroborated the importance of home programs (HPs) and program connections.² Therefore, our current objective was to compare profiles of matched dermatology applicants without HPs vs those with HPs.

We searched websites of 139 dermatology programs nationwide and found 1736 matched applicants from 2016 to 2020; of them, 323 did not have HPs. We determined program rank by research output using Doximity Residency Navigator (https://www.doximity.com/residency/). Advanced degrees (ADs) of applicants were identified using program websites and LinkedIn. A PubMed search was conducted for number of articles published by each applicant before September 15 of their match year. For applicants without HPs, we identified the senior author on each publication. The senior author publishing with an applicant most often was considered the research mentor. Two-tailed independent t tests and χ² tests were used to determine statistical significance (P<.05).

On average, matched applicants without HPs matched in lower-ranked (74.4) and smaller (12.4) programs compared with matched applicants with HPs (45.3 [P<.0001] and 15.1 [P<.0001], respectively)(eTable). The mean number of publications was similar between matched applicants with HPs and without HPs (5.64 and 4.80, respectively; P=.0525) as well as the percentage with ADs (14.7% and 11.5%, respectively; P=.0953). Overall, 14.8% of matched applicants without HPs matched at their mentors’ institutions.

Data were obtained for matched international applicants as a subset of non-HP applicants. Despite attending medical schools without associated HPs in the United States, international applicants matched at similarly ranked (44.3) and sized (15.0) programs, on average, compared with HP applicants. The mean number of publications was higher for international applicants (11.4) vs domestic applicants (5.33). International applicants more often had ADs (23.8%) and 60.1% of them held doctor of philosophy degrees. Overall, 40.5% of international applicants matched at their mentors’ institutions.

Our study suggests that matched dermatology applicants with and without HPs had similar achievements, on average, for the number of publications and percentage with ADs. However, non-HP applicants matched at lower-ranked programs than HP applicants. Therefore, applicants without HPs should strongly consider cultivating program connections, especially if they desire to match at higher-ranked dermatology programs. To illustrate, the rate of matching at research mentors’ institutions was approximately 3-times higher for international applicants than non-HP applicants overall. Despite the disadvantages of applying as international applicants, they were able to match at substantially higher-ranked dermatology programs than non-HP applicants. International applicants may have a longer time investment—the number of years from obtaining their medical degree or US medical license to matching—giving them time to produce quality research and develop meaningful relationships at an institution. Additionally, our prior study of the top 25 dermatology residencies showed that 26.2% of successful applicants matched at their research mentors’ institutions, with almost half of this subset matching at their HPs, where their mentors also practiced.² Because of the potential benefits of having program connections, applicants without HPs should seek dermatology research mentors, especially via highly beneficial in-person networking opportunities (eg, away rotations, conferences) that had previously been limited during the COVID-19 pandemic.³ Formal mentorship programs giving priority to students without HPs recently have been developed, which only begins to address the inequities in the dermatology residency application process.⁴

Study limitations include lack of resident information on 15 program websites, missed publications due to applicant name changes, not accounting for abstracts and posters, and inability to collect data on unmatched applicants.

We hope that our study alleviates some concerns that applicants without HPs may have regarding applying for dermatology residency and encourages those with a genuine interest in dermatology to pursue the specialty, provided they find a strong research mentor. Residency programs should be cognizant of the unique challenges that non-HP applicants face for matching.

To the Editor:

Dermatology is one of the most competitive residencies for matching, with a 57.5% match rate in 2022.¹ Our prior study of research-mentor relationships among matched dermatology applicants corroborated the importance of home programs (HPs) and program connections.² Therefore, our current objective was to compare profiles of matched dermatology applicants without HPs vs those with HPs.

We searched websites of 139 dermatology programs nationwide and found 1736 matched applicants from 2016 to 2020; of them, 323 did not have HPs. We determined program rank by research output using Doximity Residency Navigator (https://www.doximity.com/residency/). Advanced degrees (ADs) of applicants were identified using program websites and LinkedIn. A PubMed search was conducted for number of articles published by each applicant before September 15 of their match year. For applicants without HPs, we identified the senior author on each publication. The senior author publishing with an applicant most often was considered the research mentor. Two-tailed independent t tests and χ² tests were used to determine statistical significance (P<.05).

On average, matched applicants without HPs matched in lower-ranked (74.4) and smaller (12.4) programs compared with matched applicants with HPs (45.3 [P<.0001] and 15.1 [P<.0001], respectively)(eTable). The mean number of publications was similar between matched applicants with HPs and without HPs (5.64 and 4.80, respectively; P=.0525) as well as the percentage with ADs (14.7% and 11.5%, respectively; P=.0953). Overall, 14.8% of matched applicants without HPs matched at their mentors’ institutions.

Data were obtained for matched international applicants as a subset of non-HP applicants. Despite attending medical schools without associated HPs in the United States, international applicants matched at similarly ranked (44.3) and sized (15.0) programs, on average, compared with HP applicants. The mean number of publications was higher for international applicants (11.4) vs domestic applicants (5.33). International applicants more often had ADs (23.8%) and 60.1% of them held doctor of philosophy degrees. Overall, 40.5% of international applicants matched at their mentors’ institutions.

Our study suggests that matched dermatology applicants with and without HPs had similar achievements, on average, for the number of publications and percentage with ADs. However, non-HP applicants matched at lower-ranked programs than HP applicants. Therefore, applicants without HPs should strongly consider cultivating program connections, especially if they desire to match at higher-ranked dermatology programs. To illustrate, the rate of matching at research mentors’ institutions was approximately 3-times higher for international applicants than non-HP applicants overall. Despite the disadvantages of applying as international applicants, they were able to match at substantially higher-ranked dermatology programs than non-HP applicants. International applicants may have a longer time investment—the number of years from obtaining their medical degree or US medical license to matching—giving them time to produce quality research and develop meaningful relationships at an institution. Additionally, our prior study of the top 25 dermatology residencies showed that 26.2% of successful applicants matched at their research mentors’ institutions, with almost half of this subset matching at their HPs, where their mentors also practiced.² Because of the potential benefits of having program connections, applicants without HPs should seek dermatology research mentors, especially via highly beneficial in-person networking opportunities (eg, away rotations, conferences) that had previously been limited during the COVID-19 pandemic.³ Formal mentorship programs giving priority to students without HPs recently have been developed, which only begins to address the inequities in the dermatology residency application process.⁴

Study limitations include lack of resident information on 15 program websites, missed publications due to applicant name changes, not accounting for abstracts and posters, and inability to collect data on unmatched applicants.

We hope that our study alleviates some concerns that applicants without HPs may have regarding applying for dermatology residency and encourages those with a genuine interest in dermatology to pursue the specialty, provided they find a strong research mentor. Residency programs should be cognizant of the unique challenges that non-HP applicants face for matching.

Classification

Triatomine bugs (Triatoma) and the wheel bug (Arilus cristatus) are part of the family Reduviidae (order Hemiptera, a name that describes the sucking proboscis on the front of the insect’s head).^1,2 Both arthropods are found in multiple countries and are especially common in warmer areas, including in the United States, where they can be seen from Texas to California.^3,4 Because blood-feeding triatomines need a blood meal to survive while laying eggs and then throughout their 5 developmental nymph stages to undergo molting, they feed on mammals, such as opossums, raccoons, pack rats, and armadillos, whereas wheel bugs mainly prey on soft-bodied insects.^1,4-6

Triatoma bugs seek cutaneous blood vessels using thermosensors in their antennae to locate blood flow under the skin for feeding. After inserting the proboscis, they release nitric oxide and an anticoagulant that allows for continuous blood flow while feeding.⁷ It has been reported that triatomine bugs are not able to bite through clothing, instead seeking exposed skin, particularly near mucous membranes, such as the hands, arms, feet, head, and trunk. The name kissing bug for triatomines was coined because bites near the mouth are common.⁶ The bite typically is painless and occurs mainly at night when the insect is most active. After obtaining a blood meal, triatomine bugs seek shelter and hide in mud and daub structures, cracks, crevices, and furniture.^1,8

Unlike Triatoma species, A cristatus does not require a blood meal for development and survival, leading it to prey on soft-bodied insects. Piercing prey with the proboscis, wheel bugs inject a toxin to digest the contents and suck the digested contents through this apparatus.⁴ Because the wheel bug does not require a blood meal, it typically bites a human only for defense if it feels threatened. Unlike the painless bite of a triatomine bug, the bite of A cristatus is extremely painful; it has been described as the worst arthropod bite—worse than a hornet’s sting. The pain from the bite is caused by the toxin being injected into the skin; possible retention of the proboscis makes the pain worse.^4,9 In addition, when A cristatus is disturbed, it exudes pungent material from a pair of bright orange subrectal glands while stridulating to repulse predators.⁹

Although Triatoma species and A cristatus have separate roles in nature and vastly different impacts on health, they often are mistaken for the same arthropod when seen in nature. Features that members of Reduviidae share include large bodies (relative to their overall length); long thin legs; a narrow head; wings; and a long sucking proboscis on the front of the head.¹⁰

Characteristics that differentiate Triatoma and A cristatus species include size, color, and distinctive markings. Most triatomine bugs are 12- to 36-mm long; are dark brown or black; and have what are called tiger-stripe orange markings on the peripheral two-thirds of the body (Figure 1).¹¹ In contrast, wheel bugs commonly are bigger—measuring longer than 1.25 inches—and gray, with a cogwheel-like structure on the thorax (Figure 2).¹⁰

Dermatologic Presentation and Clinical Symptoms

The area of involved skin on patients presenting with Triatoma or A cristatus bites may resemble other insect bites. Many bites from Triatoma bugs and A cristatus initially present as an erythematous, raised, pruritic papule with a central punctum that is visible because of the involvement of the proboscis. However, other presentations of bites from both arthropods have been reported^4,6,7: grouped vesicles on an erythematous base; indurated, giant, urticarial-type wheels measuring 10 to 15 mm in diameter; and hemorrhagic bullous nodules (Figure 3). Associated lymphangitis or lymphadenitis is typical of the latter 2 variations.⁶ These variations in presentation can be mistaken for other causes of similarly presenting lesions, such as shingles or spider bites, leading to delayed or missed diagnosis.

Patients may present with a single bite or multiple bites due to the feeding pattern of Triatoma bugs; if the host moves or disrupts its feeding, the arthropod takes multiple bites to finish feeding.⁸ In comparison, 4 common variations of wheel bug bites have been reported: (1) a painful bite without complications; (2) a cutaneous horn and papilloma at the site of toxin injection; (3) a necrotic ulcer around the central punctum caused by injected toxin; and (4) an abscess under the central punctum due to secondary infection.⁴

Anaphylaxis—Although the bites of Triatoma and A cristatus present differently, both can cause anaphylaxis. Triatoma is implicated more often than A cristatus as the cause of anaphylaxis.¹² In fact, Triatoma bites are among the more common causes of anaphylaxis from bug bites, with multiple cases of these reactions reported in the literature.^12,13

Symptoms of Triatoma anaphylaxis include acute-onset urticarial rash, flushing, dyspnea, wheezing, nausea, vomiting, and localized edema.² The cause of anaphylaxis is proteins in Triatoma saliva, including 20-kDa procalin, which incites the systemic reaction. Other potential causes of anaphylaxis include serine protease, which has similarities to salivary protein and desmoglein in humans.¹¹

The degree of reaction to a bite depends on the patient's sensitization to antigenic proteins in each insect’s saliva.^4,6 Patients who have a bite from a triatomine bug are at risk for subsequent bites, as household infestation is likely due to the pliability of the insect, allowing it to hide in small spaces unnoticed.⁸ In the case of a bite from Triatoma or A cristatus, sensitization may lead to severe and worsening reactions with subsequent bites, which ultimately can result in life-threatening anaphylaxis.^1,6

Treatment and Prevention

Treatment of Triatoma and A cristatus bites depends on the severity of the patient’s reaction to the bite. A local reaction to a bite from either insect can be treated supportively with local corticosteroids and antihistamines.³ If the patient is sensitized to proteins associated with a bite, standard anaphylaxis treatment such as epinephrine and intravenous antihistamines may be indicated.¹⁴ Secondary infection can be treated with antibiotics; a formed abscess might need to be drained or debrided.¹⁵

There’s No Place Like Home—Because Triatoma bugs have a pliable exoskeleton and can squeeze into small spaces, they commonly infest dwellings where they find multiple attractants: light, heat, carbon dioxide, and lactic acid.⁸ The more household occupants (including pets), the higher the levels of carbon dioxide and lactic acid, thus the greater the attraction. Infestation of a home can lead to the spread of diseases harbored by Triatoma, including Chagas disease, which is caused by the parasite Trypanosoma cruzi.⁵

Preventive measures can be taken to reduce the risk and extent of home infestation by Triatoma bugs, including insecticides, a solid foundation, window screens, air conditioning, sealing of cracks and crevices, outdoor light management, and removal of clutter throughout the house.⁸ Because Triatoma bugs cannot bite through clothing, protective clothing and bug repellent on exposed skin can be employed. Another degree of protection is offered by pest management, especially control of rodents by removing food, water, and nests in areas where triatomine bugs feed off of that population.^8,14

Unlike triatomine bugs, wheel bugs tend not to invade houses; therefore, these preventive measures are unnecessary. If a wheel bug is identified, do not engage the arthropod due to the defensive nature of its attack.^4,9 Such deliberate avoidance should ensure protection from the wheel bug’s painful bite.

Medical Complications

Although triatomine bugs and wheel bugs are in the same taxonomic family, subsequent infection is unique to Triatoma bugs because they need a blood meal to survive. Because Triatoma bugs feed on mammals, they present an increased opportunity for transmitting the causative agents of infection from hosts on which they have fed.¹² The principal parasite transmitted by triatomines is T cruzi, which causes Chagas disease and lives in the gastrointestinal (GI) tract of the insect.⁵ When a triatomine bug seeks out a mucosal surface to bite, including the mouth, it defecates and urinates during or shortly after feeding, leading to contamination of the initial wound or mucosal surfaces. In addition, Triatoma bugs are vectors for transmission of Serratia marcescans, Bartonella henselae, and Mycobacterium leprae.¹⁶

Chagas Disease—This infection has 3 stages: acute, intermediate, and chronic.⁵ The acute stage can present with symptoms of conjunctivitis, fever, lymphadenopathy, hepatosplenomegaly, and anemia. The intermediate stage typically is asymptomatic. The chronic stage usually involves the heart and GI tract and causes cardiac aneurysms, cardiomegaly, megacolon, and megaesophagus. Initial symptoms can be a localized nodule (chagoma) at the inoculation site, fever, fatigue, lymphadenopathy, and hepatosplenomegaly.² Unilateral palpebral edema with associated lymphadenopathy (Romaña sign) also can be seen—not to be confused with bilateral swelling in an acute reaction to an insect bite. Romaña sign is pathognomonic of T cruzi infection; bilateral palpebral swelling is typical of an allergic reaction.¹²

Identification of a triatomine bite is the first step in diagnosing Chagas disease, which can be life-threatening. Among chronic carriers of Chagas disease, 30% develop GI and cardiac symptoms, of which 20% to 30% develop cardiomyopathy, with serious symptoms that present 10 to 20 years after the asymptomatic intermediate phase.²

Chagas disease is endemic to Central and South America but is also seen in North America; 28,000 new cases are reported annually in South America and North America combined. Human migration from endemic areas and from rural to urban areas has promoted the spread of Chagas disease.² However, patients in the United States have a relatively low risk for Chagas disease, largely because of the quality of housing construction and use of insecticides.

Treatment options for Chagas disease include nifurtimox and benznidazole. Without treatment, the host immune response typically controls acute replication of the parasite but will lead to a chronic state, ultimately involving the heart and GI tract.⁵

Classification

Triatomine bugs (Triatoma) and the wheel bug (Arilus cristatus) are part of the family Reduviidae (order Hemiptera, a name that describes the sucking proboscis on the front of the insect’s head).^1,2 Both arthropods are found in multiple countries and are especially common in warmer areas, including in the United States, where they can be seen from Texas to California.^3,4 Because blood-feeding triatomines need a blood meal to survive while laying eggs and then throughout their 5 developmental nymph stages to undergo molting, they feed on mammals, such as opossums, raccoons, pack rats, and armadillos, whereas wheel bugs mainly prey on soft-bodied insects.^1,4-6

Triatoma bugs seek cutaneous blood vessels using thermosensors in their antennae to locate blood flow under the skin for feeding. After inserting the proboscis, they release nitric oxide and an anticoagulant that allows for continuous blood flow while feeding.⁷ It has been reported that triatomine bugs are not able to bite through clothing, instead seeking exposed skin, particularly near mucous membranes, such as the hands, arms, feet, head, and trunk. The name kissing bug for triatomines was coined because bites near the mouth are common.⁶ The bite typically is painless and occurs mainly at night when the insect is most active. After obtaining a blood meal, triatomine bugs seek shelter and hide in mud and daub structures, cracks, crevices, and furniture.^1,8

Unlike Triatoma species, A cristatus does not require a blood meal for development and survival, leading it to prey on soft-bodied insects. Piercing prey with the proboscis, wheel bugs inject a toxin to digest the contents and suck the digested contents through this apparatus.⁴ Because the wheel bug does not require a blood meal, it typically bites a human only for defense if it feels threatened. Unlike the painless bite of a triatomine bug, the bite of A cristatus is extremely painful; it has been described as the worst arthropod bite—worse than a hornet’s sting. The pain from the bite is caused by the toxin being injected into the skin; possible retention of the proboscis makes the pain worse.^4,9 In addition, when A cristatus is disturbed, it exudes pungent material from a pair of bright orange subrectal glands while stridulating to repulse predators.⁹

Although Triatoma species and A cristatus have separate roles in nature and vastly different impacts on health, they often are mistaken for the same arthropod when seen in nature. Features that members of Reduviidae share include large bodies (relative to their overall length); long thin legs; a narrow head; wings; and a long sucking proboscis on the front of the head.¹⁰

Characteristics that differentiate Triatoma and A cristatus species include size, color, and distinctive markings. Most triatomine bugs are 12- to 36-mm long; are dark brown or black; and have what are called tiger-stripe orange markings on the peripheral two-thirds of the body (Figure 1).¹¹ In contrast, wheel bugs commonly are bigger—measuring longer than 1.25 inches—and gray, with a cogwheel-like structure on the thorax (Figure 2).¹⁰

Dermatologic Presentation and Clinical Symptoms

The area of involved skin on patients presenting with Triatoma or A cristatus bites may resemble other insect bites. Many bites from Triatoma bugs and A cristatus initially present as an erythematous, raised, pruritic papule with a central punctum that is visible because of the involvement of the proboscis. However, other presentations of bites from both arthropods have been reported^4,6,7: grouped vesicles on an erythematous base; indurated, giant, urticarial-type wheels measuring 10 to 15 mm in diameter; and hemorrhagic bullous nodules (Figure 3). Associated lymphangitis or lymphadenitis is typical of the latter 2 variations.⁶ These variations in presentation can be mistaken for other causes of similarly presenting lesions, such as shingles or spider bites, leading to delayed or missed diagnosis.

Patients may present with a single bite or multiple bites due to the feeding pattern of Triatoma bugs; if the host moves or disrupts its feeding, the arthropod takes multiple bites to finish feeding.⁸ In comparison, 4 common variations of wheel bug bites have been reported: (1) a painful bite without complications; (2) a cutaneous horn and papilloma at the site of toxin injection; (3) a necrotic ulcer around the central punctum caused by injected toxin; and (4) an abscess under the central punctum due to secondary infection.⁴

Anaphylaxis—Although the bites of Triatoma and A cristatus present differently, both can cause anaphylaxis. Triatoma is implicated more often than A cristatus as the cause of anaphylaxis.¹² In fact, Triatoma bites are among the more common causes of anaphylaxis from bug bites, with multiple cases of these reactions reported in the literature.^12,13

Symptoms of Triatoma anaphylaxis include acute-onset urticarial rash, flushing, dyspnea, wheezing, nausea, vomiting, and localized edema.² The cause of anaphylaxis is proteins in Triatoma saliva, including 20-kDa procalin, which incites the systemic reaction. Other potential causes of anaphylaxis include serine protease, which has similarities to salivary protein and desmoglein in humans.¹¹

The degree of reaction to a bite depends on the patient's sensitization to antigenic proteins in each insect’s saliva.^4,6 Patients who have a bite from a triatomine bug are at risk for subsequent bites, as household infestation is likely due to the pliability of the insect, allowing it to hide in small spaces unnoticed.⁸ In the case of a bite from Triatoma or A cristatus, sensitization may lead to severe and worsening reactions with subsequent bites, which ultimately can result in life-threatening anaphylaxis.^1,6

Treatment and Prevention

Treatment of Triatoma and A cristatus bites depends on the severity of the patient’s reaction to the bite. A local reaction to a bite from either insect can be treated supportively with local corticosteroids and antihistamines.³ If the patient is sensitized to proteins associated with a bite, standard anaphylaxis treatment such as epinephrine and intravenous antihistamines may be indicated.¹⁴ Secondary infection can be treated with antibiotics; a formed abscess might need to be drained or debrided.¹⁵

There’s No Place Like Home—Because Triatoma bugs have a pliable exoskeleton and can squeeze into small spaces, they commonly infest dwellings where they find multiple attractants: light, heat, carbon dioxide, and lactic acid.⁸ The more household occupants (including pets), the higher the levels of carbon dioxide and lactic acid, thus the greater the attraction. Infestation of a home can lead to the spread of diseases harbored by Triatoma, including Chagas disease, which is caused by the parasite Trypanosoma cruzi.⁵

Preventive measures can be taken to reduce the risk and extent of home infestation by Triatoma bugs, including insecticides, a solid foundation, window screens, air conditioning, sealing of cracks and crevices, outdoor light management, and removal of clutter throughout the house.⁸ Because Triatoma bugs cannot bite through clothing, protective clothing and bug repellent on exposed skin can be employed. Another degree of protection is offered by pest management, especially control of rodents by removing food, water, and nests in areas where triatomine bugs feed off of that population.^8,14

Unlike triatomine bugs, wheel bugs tend not to invade houses; therefore, these preventive measures are unnecessary. If a wheel bug is identified, do not engage the arthropod due to the defensive nature of its attack.^4,9 Such deliberate avoidance should ensure protection from the wheel bug’s painful bite.

Medical Complications

Although triatomine bugs and wheel bugs are in the same taxonomic family, subsequent infection is unique to Triatoma bugs because they need a blood meal to survive. Because Triatoma bugs feed on mammals, they present an increased opportunity for transmitting the causative agents of infection from hosts on which they have fed.¹² The principal parasite transmitted by triatomines is T cruzi, which causes Chagas disease and lives in the gastrointestinal (GI) tract of the insect.⁵ When a triatomine bug seeks out a mucosal surface to bite, including the mouth, it defecates and urinates during or shortly after feeding, leading to contamination of the initial wound or mucosal surfaces. In addition, Triatoma bugs are vectors for transmission of Serratia marcescans, Bartonella henselae, and Mycobacterium leprae.¹⁶

Chagas Disease—This infection has 3 stages: acute, intermediate, and chronic.⁵ The acute stage can present with symptoms of conjunctivitis, fever, lymphadenopathy, hepatosplenomegaly, and anemia. The intermediate stage typically is asymptomatic. The chronic stage usually involves the heart and GI tract and causes cardiac aneurysms, cardiomegaly, megacolon, and megaesophagus. Initial symptoms can be a localized nodule (chagoma) at the inoculation site, fever, fatigue, lymphadenopathy, and hepatosplenomegaly.² Unilateral palpebral edema with associated lymphadenopathy (Romaña sign) also can be seen—not to be confused with bilateral swelling in an acute reaction to an insect bite. Romaña sign is pathognomonic of T cruzi infection; bilateral palpebral swelling is typical of an allergic reaction.¹²

Identification of a triatomine bite is the first step in diagnosing Chagas disease, which can be life-threatening. Among chronic carriers of Chagas disease, 30% develop GI and cardiac symptoms, of which 20% to 30% develop cardiomyopathy, with serious symptoms that present 10 to 20 years after the asymptomatic intermediate phase.²

Chagas disease is endemic to Central and South America but is also seen in North America; 28,000 new cases are reported annually in South America and North America combined. Human migration from endemic areas and from rural to urban areas has promoted the spread of Chagas disease.² However, patients in the United States have a relatively low risk for Chagas disease, largely because of the quality of housing construction and use of insecticides.

Treatment options for Chagas disease include nifurtimox and benznidazole. Without treatment, the host immune response typically controls acute replication of the parasite but will lead to a chronic state, ultimately involving the heart and GI tract.⁵

Classification

Triatomine bugs (Triatoma) and the wheel bug (Arilus cristatus) are part of the family Reduviidae (order Hemiptera, a name that describes the sucking proboscis on the front of the insect’s head).^1,2 Both arthropods are found in multiple countries and are especially common in warmer areas, including in the United States, where they can be seen from Texas to California.^3,4 Because blood-feeding triatomines need a blood meal to survive while laying eggs and then throughout their 5 developmental nymph stages to undergo molting, they feed on mammals, such as opossums, raccoons, pack rats, and armadillos, whereas wheel bugs mainly prey on soft-bodied insects.^1,4-6

Triatoma bugs seek cutaneous blood vessels using thermosensors in their antennae to locate blood flow under the skin for feeding. After inserting the proboscis, they release nitric oxide and an anticoagulant that allows for continuous blood flow while feeding.⁷ It has been reported that triatomine bugs are not able to bite through clothing, instead seeking exposed skin, particularly near mucous membranes, such as the hands, arms, feet, head, and trunk. The name kissing bug for triatomines was coined because bites near the mouth are common.⁶ The bite typically is painless and occurs mainly at night when the insect is most active. After obtaining a blood meal, triatomine bugs seek shelter and hide in mud and daub structures, cracks, crevices, and furniture.^1,8

Unlike Triatoma species, A cristatus does not require a blood meal for development and survival, leading it to prey on soft-bodied insects. Piercing prey with the proboscis, wheel bugs inject a toxin to digest the contents and suck the digested contents through this apparatus.⁴ Because the wheel bug does not require a blood meal, it typically bites a human only for defense if it feels threatened. Unlike the painless bite of a triatomine bug, the bite of A cristatus is extremely painful; it has been described as the worst arthropod bite—worse than a hornet’s sting. The pain from the bite is caused by the toxin being injected into the skin; possible retention of the proboscis makes the pain worse.^4,9 In addition, when A cristatus is disturbed, it exudes pungent material from a pair of bright orange subrectal glands while stridulating to repulse predators.⁹

Although Triatoma species and A cristatus have separate roles in nature and vastly different impacts on health, they often are mistaken for the same arthropod when seen in nature. Features that members of Reduviidae share include large bodies (relative to their overall length); long thin legs; a narrow head; wings; and a long sucking proboscis on the front of the head.¹⁰

Characteristics that differentiate Triatoma and A cristatus species include size, color, and distinctive markings. Most triatomine bugs are 12- to 36-mm long; are dark brown or black; and have what are called tiger-stripe orange markings on the peripheral two-thirds of the body (Figure 1).¹¹ In contrast, wheel bugs commonly are bigger—measuring longer than 1.25 inches—and gray, with a cogwheel-like structure on the thorax (Figure 2).¹⁰

Dermatologic Presentation and Clinical Symptoms

The area of involved skin on patients presenting with Triatoma or A cristatus bites may resemble other insect bites. Many bites from Triatoma bugs and A cristatus initially present as an erythematous, raised, pruritic papule with a central punctum that is visible because of the involvement of the proboscis. However, other presentations of bites from both arthropods have been reported^4,6,7: grouped vesicles on an erythematous base; indurated, giant, urticarial-type wheels measuring 10 to 15 mm in diameter; and hemorrhagic bullous nodules (Figure 3). Associated lymphangitis or lymphadenitis is typical of the latter 2 variations.⁶ These variations in presentation can be mistaken for other causes of similarly presenting lesions, such as shingles or spider bites, leading to delayed or missed diagnosis.

Patients may present with a single bite or multiple bites due to the feeding pattern of Triatoma bugs; if the host moves or disrupts its feeding, the arthropod takes multiple bites to finish feeding.⁸ In comparison, 4 common variations of wheel bug bites have been reported: (1) a painful bite without complications; (2) a cutaneous horn and papilloma at the site of toxin injection; (3) a necrotic ulcer around the central punctum caused by injected toxin; and (4) an abscess under the central punctum due to secondary infection.⁴

Anaphylaxis—Although the bites of Triatoma and A cristatus present differently, both can cause anaphylaxis. Triatoma is implicated more often than A cristatus as the cause of anaphylaxis.¹² In fact, Triatoma bites are among the more common causes of anaphylaxis from bug bites, with multiple cases of these reactions reported in the literature.^12,13

Symptoms of Triatoma anaphylaxis include acute-onset urticarial rash, flushing, dyspnea, wheezing, nausea, vomiting, and localized edema.² The cause of anaphylaxis is proteins in Triatoma saliva, including 20-kDa procalin, which incites the systemic reaction. Other potential causes of anaphylaxis include serine protease, which has similarities to salivary protein and desmoglein in humans.¹¹

The degree of reaction to a bite depends on the patient's sensitization to antigenic proteins in each insect’s saliva.^4,6 Patients who have a bite from a triatomine bug are at risk for subsequent bites, as household infestation is likely due to the pliability of the insect, allowing it to hide in small spaces unnoticed.⁸ In the case of a bite from Triatoma or A cristatus, sensitization may lead to severe and worsening reactions with subsequent bites, which ultimately can result in life-threatening anaphylaxis.^1,6

Treatment and Prevention

Treatment of Triatoma and A cristatus bites depends on the severity of the patient’s reaction to the bite. A local reaction to a bite from either insect can be treated supportively with local corticosteroids and antihistamines.³ If the patient is sensitized to proteins associated with a bite, standard anaphylaxis treatment such as epinephrine and intravenous antihistamines may be indicated.¹⁴ Secondary infection can be treated with antibiotics; a formed abscess might need to be drained or debrided.¹⁵

There’s No Place Like Home—Because Triatoma bugs have a pliable exoskeleton and can squeeze into small spaces, they commonly infest dwellings where they find multiple attractants: light, heat, carbon dioxide, and lactic acid.⁸ The more household occupants (including pets), the higher the levels of carbon dioxide and lactic acid, thus the greater the attraction. Infestation of a home can lead to the spread of diseases harbored by Triatoma, including Chagas disease, which is caused by the parasite Trypanosoma cruzi.⁵

Preventive measures can be taken to reduce the risk and extent of home infestation by Triatoma bugs, including insecticides, a solid foundation, window screens, air conditioning, sealing of cracks and crevices, outdoor light management, and removal of clutter throughout the house.⁸ Because Triatoma bugs cannot bite through clothing, protective clothing and bug repellent on exposed skin can be employed. Another degree of protection is offered by pest management, especially control of rodents by removing food, water, and nests in areas where triatomine bugs feed off of that population.^8,14

Unlike triatomine bugs, wheel bugs tend not to invade houses; therefore, these preventive measures are unnecessary. If a wheel bug is identified, do not engage the arthropod due to the defensive nature of its attack.^4,9 Such deliberate avoidance should ensure protection from the wheel bug’s painful bite.

Medical Complications

Although triatomine bugs and wheel bugs are in the same taxonomic family, subsequent infection is unique to Triatoma bugs because they need a blood meal to survive. Because Triatoma bugs feed on mammals, they present an increased opportunity for transmitting the causative agents of infection from hosts on which they have fed.¹² The principal parasite transmitted by triatomines is T cruzi, which causes Chagas disease and lives in the gastrointestinal (GI) tract of the insect.⁵ When a triatomine bug seeks out a mucosal surface to bite, including the mouth, it defecates and urinates during or shortly after feeding, leading to contamination of the initial wound or mucosal surfaces. In addition, Triatoma bugs are vectors for transmission of Serratia marcescans, Bartonella henselae, and Mycobacterium leprae.¹⁶

Chagas Disease—This infection has 3 stages: acute, intermediate, and chronic.⁵ The acute stage can present with symptoms of conjunctivitis, fever, lymphadenopathy, hepatosplenomegaly, and anemia. The intermediate stage typically is asymptomatic. The chronic stage usually involves the heart and GI tract and causes cardiac aneurysms, cardiomegaly, megacolon, and megaesophagus. Initial symptoms can be a localized nodule (chagoma) at the inoculation site, fever, fatigue, lymphadenopathy, and hepatosplenomegaly.² Unilateral palpebral edema with associated lymphadenopathy (Romaña sign) also can be seen—not to be confused with bilateral swelling in an acute reaction to an insect bite. Romaña sign is pathognomonic of T cruzi infection; bilateral palpebral swelling is typical of an allergic reaction.¹²

Identification of a triatomine bite is the first step in diagnosing Chagas disease, which can be life-threatening. Among chronic carriers of Chagas disease, 30% develop GI and cardiac symptoms, of which 20% to 30% develop cardiomyopathy, with serious symptoms that present 10 to 20 years after the asymptomatic intermediate phase.²

Chagas disease is endemic to Central and South America but is also seen in North America; 28,000 new cases are reported annually in South America and North America combined. Human migration from endemic areas and from rural to urban areas has promoted the spread of Chagas disease.² However, patients in the United States have a relatively low risk for Chagas disease, largely because of the quality of housing construction and use of insecticides.

Treatment options for Chagas disease include nifurtimox and benznidazole. Without treatment, the host immune response typically controls acute replication of the parasite but will lead to a chronic state, ultimately involving the heart and GI tract.⁵