Heidi Splete

Statin use for a minimum of 3 months was significantly associated with an increased risk of skin and soft tissue infections (SSTIs), according to a sequence symmetry analysis of prescription claims over a 10-year period reported in the British Journal of Clinical Pharmacology.

In the study, statin use for as little as 91 days was linked with elevated risks of SSTIs and diabetes. However, the increased risk of infection was seen in individuals who did and did not develop diabetes, wrote Humphrey Ko, of the school of pharmacy and biomedical sciences, Curtin University, Perth, Australia, and colleagues.

The current literature on the impact of statins on SSTIs is conflicted, they noted. Previous research shows that statins “may reduce the risk of community-acquired [Staphylococcus aureus] bacteremia and exert antibacterial effects against S. aureus,” and therefore may have potential for reducing SSTI risk “or evolve into promising novel treatments for SSTIs,” the researchers said; they noted, however, that other data show that statins may induce new-onset diabetes.

They examined prescription claims (for statins, antidiabetic medications, and antistaphylococcal antibiotics) from 2001 to 2011 from the Australian Department of Veterans’ Affairs that included more than 228,000 veterans, war widows, and widowers. Prescriptions for antistaphylococcal antibiotics were used as a marker of SSTIs.

Overall, statins were significantly associated with an increased risk of SSTIs at 91 days (adjusted sequence ratio, 1.40). The risk of SSTIs from statin use was similar at 182 (ASR, 1.41) and 365 days (ASR, 1.40). In this case, the ASRs represent the incidence rate ratios of prescribing antibiotics in statin-exposed versus statin-nonexposed person-time.

Statins were associated with a significantly increased risk of new onset diabetes, but the SSTI risk was not significantly different between statin users with and without diabetes. Statin users who did not have diabetes had significant SSTI risks at 91, 182, and 365 days (ASR, 1.39, 1.41, and 1.37, respectively) and statin users with diabetes had similarly significant risks of SSTIs (ASR,1.43, 1.42, and 1.49, respectively).

In addition, socioeconomic status appeared to have no significant effect on the relationship between statin use, SSTIs, and diabetes, the researchers noted.

The findings were limited by several factors including the inability to account for patient compliance in taking the medications, a lack of dosage data to determine the impact of dosage on outcomes, and potential confounding by the presence of diabetes, they said. However, the results suggest that “it would seem prudent for clinicians to monitor blood glucose levels of statin users who are predisposed to diabetes, and be mindful of possible increased SSTI risks in such patients,” they concluded. Statins, they added, “may increase SSTI risk via direct or indirect mechanisms.”

More clinical trials are needed to confirm the mechanisms, and “to ascertain the effect of statins on gut dysbiosis, impaired bile acid metabolism, vitamin D levels, and cholesterol inhibition on skin function,” they wrote.

The study was supported in part by the Australian Government Research Training Program Scholarship, the Curtin Health Innovation Research Institute Biosciences Research Precinct Core Facility, and the School of Pharmacy and Biomedical Sciences (Curtin University). The researchers had no financial conflicts to disclose.

SOURCE: Ko H et al. Br J Clin Pharmacol. 2019 Oct 9. doi: 10.1111/bcp.14077.

Statin use for a minimum of 3 months was significantly associated with an increased risk of skin and soft tissue infections (SSTIs), according to a sequence symmetry analysis of prescription claims over a 10-year period reported in the British Journal of Clinical Pharmacology.

In the study, statin use for as little as 91 days was linked with elevated risks of SSTIs and diabetes. However, the increased risk of infection was seen in individuals who did and did not develop diabetes, wrote Humphrey Ko, of the school of pharmacy and biomedical sciences, Curtin University, Perth, Australia, and colleagues.

The current literature on the impact of statins on SSTIs is conflicted, they noted. Previous research shows that statins “may reduce the risk of community-acquired [Staphylococcus aureus] bacteremia and exert antibacterial effects against S. aureus,” and therefore may have potential for reducing SSTI risk “or evolve into promising novel treatments for SSTIs,” the researchers said; they noted, however, that other data show that statins may induce new-onset diabetes.

They examined prescription claims (for statins, antidiabetic medications, and antistaphylococcal antibiotics) from 2001 to 2011 from the Australian Department of Veterans’ Affairs that included more than 228,000 veterans, war widows, and widowers. Prescriptions for antistaphylococcal antibiotics were used as a marker of SSTIs.

Overall, statins were significantly associated with an increased risk of SSTIs at 91 days (adjusted sequence ratio, 1.40). The risk of SSTIs from statin use was similar at 182 (ASR, 1.41) and 365 days (ASR, 1.40). In this case, the ASRs represent the incidence rate ratios of prescribing antibiotics in statin-exposed versus statin-nonexposed person-time.

Statins were associated with a significantly increased risk of new onset diabetes, but the SSTI risk was not significantly different between statin users with and without diabetes. Statin users who did not have diabetes had significant SSTI risks at 91, 182, and 365 days (ASR, 1.39, 1.41, and 1.37, respectively) and statin users with diabetes had similarly significant risks of SSTIs (ASR,1.43, 1.42, and 1.49, respectively).

In addition, socioeconomic status appeared to have no significant effect on the relationship between statin use, SSTIs, and diabetes, the researchers noted.

The findings were limited by several factors including the inability to account for patient compliance in taking the medications, a lack of dosage data to determine the impact of dosage on outcomes, and potential confounding by the presence of diabetes, they said. However, the results suggest that “it would seem prudent for clinicians to monitor blood glucose levels of statin users who are predisposed to diabetes, and be mindful of possible increased SSTI risks in such patients,” they concluded. Statins, they added, “may increase SSTI risk via direct or indirect mechanisms.”

More clinical trials are needed to confirm the mechanisms, and “to ascertain the effect of statins on gut dysbiosis, impaired bile acid metabolism, vitamin D levels, and cholesterol inhibition on skin function,” they wrote.

The study was supported in part by the Australian Government Research Training Program Scholarship, the Curtin Health Innovation Research Institute Biosciences Research Precinct Core Facility, and the School of Pharmacy and Biomedical Sciences (Curtin University). The researchers had no financial conflicts to disclose.

SOURCE: Ko H et al. Br J Clin Pharmacol. 2019 Oct 9. doi: 10.1111/bcp.14077.

Statin use for a minimum of 3 months was significantly associated with an increased risk of skin and soft tissue infections (SSTIs), according to a sequence symmetry analysis of prescription claims over a 10-year period reported in the British Journal of Clinical Pharmacology.

In the study, statin use for as little as 91 days was linked with elevated risks of SSTIs and diabetes. However, the increased risk of infection was seen in individuals who did and did not develop diabetes, wrote Humphrey Ko, of the school of pharmacy and biomedical sciences, Curtin University, Perth, Australia, and colleagues.

The current literature on the impact of statins on SSTIs is conflicted, they noted. Previous research shows that statins “may reduce the risk of community-acquired [Staphylococcus aureus] bacteremia and exert antibacterial effects against S. aureus,” and therefore may have potential for reducing SSTI risk “or evolve into promising novel treatments for SSTIs,” the researchers said; they noted, however, that other data show that statins may induce new-onset diabetes.

They examined prescription claims (for statins, antidiabetic medications, and antistaphylococcal antibiotics) from 2001 to 2011 from the Australian Department of Veterans’ Affairs that included more than 228,000 veterans, war widows, and widowers. Prescriptions for antistaphylococcal antibiotics were used as a marker of SSTIs.

Overall, statins were significantly associated with an increased risk of SSTIs at 91 days (adjusted sequence ratio, 1.40). The risk of SSTIs from statin use was similar at 182 (ASR, 1.41) and 365 days (ASR, 1.40). In this case, the ASRs represent the incidence rate ratios of prescribing antibiotics in statin-exposed versus statin-nonexposed person-time.

Statins were associated with a significantly increased risk of new onset diabetes, but the SSTI risk was not significantly different between statin users with and without diabetes. Statin users who did not have diabetes had significant SSTI risks at 91, 182, and 365 days (ASR, 1.39, 1.41, and 1.37, respectively) and statin users with diabetes had similarly significant risks of SSTIs (ASR,1.43, 1.42, and 1.49, respectively).

In addition, socioeconomic status appeared to have no significant effect on the relationship between statin use, SSTIs, and diabetes, the researchers noted.

The findings were limited by several factors including the inability to account for patient compliance in taking the medications, a lack of dosage data to determine the impact of dosage on outcomes, and potential confounding by the presence of diabetes, they said. However, the results suggest that “it would seem prudent for clinicians to monitor blood glucose levels of statin users who are predisposed to diabetes, and be mindful of possible increased SSTI risks in such patients,” they concluded. Statins, they added, “may increase SSTI risk via direct or indirect mechanisms.”

More clinical trials are needed to confirm the mechanisms, and “to ascertain the effect of statins on gut dysbiosis, impaired bile acid metabolism, vitamin D levels, and cholesterol inhibition on skin function,” they wrote.

The study was supported in part by the Australian Government Research Training Program Scholarship, the Curtin Health Innovation Research Institute Biosciences Research Precinct Core Facility, and the School of Pharmacy and Biomedical Sciences (Curtin University). The researchers had no financial conflicts to disclose.

SOURCE: Ko H et al. Br J Clin Pharmacol. 2019 Oct 9. doi: 10.1111/bcp.14077.

Adult athletes who underwent knee surgery and had higher levels of preoperative pain catastrophizing were significantly less likely to return to preinjury activity, based on data from 101 individuals.

decade3d/Thinkstock

Pain is highly subjective, and pain perception can play a role in postsurgical outcomes, but the relationships among preoperative pain perception and short-term outcomes including returning to sports have not been well-studied, wrote Joshua S. Everhart, MD, of The Ohio State University Wexner Medical Center, Columbus, and colleagues.

In a study published in the Journal of Science and Medicine in Sport, the researchers assessed 101 adult athletes who underwent knee surgery at a single center. The average age of the patients was 33 years, and 49 were women.

Pain perception and coping were assessed via the McGill Pain questionnaire (SF-MPQ), Pain Catastrophizing Scale (PCS), Pain Coping Measure (PCM), and the brief COPE subscales of acceptance, denial, positive reframing, and use of instrumental support.

Patients who were severe pain catastrophizers (defined as scores greater than 36 on the Pain Catastrophizing Scale) had increased odds of not returning to a similar level of sport (OR 11.3).

Higher scores on the brief COPE subscale of “use of instrumental support” (instruments designed to help patients cope with pain) had a protective effect on returning to preinjury activity (OR 0.72 per point increase). However, higher COPE-denial scores were significantly associated with lower odds of improvement in kinesiophobia (OR 0.43).

Patients with greater levels of problem-focused coping had significantly greater improvement in International Knee Documentation Committee (IKDC) scores, as did patients who were older and more active.

“Specific coping strategies appear to moderate the effect of pain perceptions on postoperative outcomes, with some coping strategies being protective and others being harmful,” the researchers said.

The findings were limited by several factors including the use of multiple comparisons, the inability to assess the impact of pain perception after knee rehabilitation independent of surgery, and the small number of some uncommon procedures, the researchers noted.

However, the results suggest that “recognition of pain perception and coping styles early on in treatment may help sports medicine providers identify patients at risk for an unsatisfactory subjective outcome,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Everhart JS et al. J Sci Med Sport. 2019. doi: 10.1016/j.jsams.2019.09.011.

Adult athletes who underwent knee surgery and had higher levels of preoperative pain catastrophizing were significantly less likely to return to preinjury activity, based on data from 101 individuals.

decade3d/Thinkstock

Pain is highly subjective, and pain perception can play a role in postsurgical outcomes, but the relationships among preoperative pain perception and short-term outcomes including returning to sports have not been well-studied, wrote Joshua S. Everhart, MD, of The Ohio State University Wexner Medical Center, Columbus, and colleagues.

In a study published in the Journal of Science and Medicine in Sport, the researchers assessed 101 adult athletes who underwent knee surgery at a single center. The average age of the patients was 33 years, and 49 were women.

Pain perception and coping were assessed via the McGill Pain questionnaire (SF-MPQ), Pain Catastrophizing Scale (PCS), Pain Coping Measure (PCM), and the brief COPE subscales of acceptance, denial, positive reframing, and use of instrumental support.

Patients who were severe pain catastrophizers (defined as scores greater than 36 on the Pain Catastrophizing Scale) had increased odds of not returning to a similar level of sport (OR 11.3).

Higher scores on the brief COPE subscale of “use of instrumental support” (instruments designed to help patients cope with pain) had a protective effect on returning to preinjury activity (OR 0.72 per point increase). However, higher COPE-denial scores were significantly associated with lower odds of improvement in kinesiophobia (OR 0.43).

Patients with greater levels of problem-focused coping had significantly greater improvement in International Knee Documentation Committee (IKDC) scores, as did patients who were older and more active.

“Specific coping strategies appear to moderate the effect of pain perceptions on postoperative outcomes, with some coping strategies being protective and others being harmful,” the researchers said.

The findings were limited by several factors including the use of multiple comparisons, the inability to assess the impact of pain perception after knee rehabilitation independent of surgery, and the small number of some uncommon procedures, the researchers noted.

However, the results suggest that “recognition of pain perception and coping styles early on in treatment may help sports medicine providers identify patients at risk for an unsatisfactory subjective outcome,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Everhart JS et al. J Sci Med Sport. 2019. doi: 10.1016/j.jsams.2019.09.011.

Adult athletes who underwent knee surgery and had higher levels of preoperative pain catastrophizing were significantly less likely to return to preinjury activity, based on data from 101 individuals.

decade3d/Thinkstock

Pain is highly subjective, and pain perception can play a role in postsurgical outcomes, but the relationships among preoperative pain perception and short-term outcomes including returning to sports have not been well-studied, wrote Joshua S. Everhart, MD, of The Ohio State University Wexner Medical Center, Columbus, and colleagues.

In a study published in the Journal of Science and Medicine in Sport, the researchers assessed 101 adult athletes who underwent knee surgery at a single center. The average age of the patients was 33 years, and 49 were women.

Pain perception and coping were assessed via the McGill Pain questionnaire (SF-MPQ), Pain Catastrophizing Scale (PCS), Pain Coping Measure (PCM), and the brief COPE subscales of acceptance, denial, positive reframing, and use of instrumental support.

Patients who were severe pain catastrophizers (defined as scores greater than 36 on the Pain Catastrophizing Scale) had increased odds of not returning to a similar level of sport (OR 11.3).

Higher scores on the brief COPE subscale of “use of instrumental support” (instruments designed to help patients cope with pain) had a protective effect on returning to preinjury activity (OR 0.72 per point increase). However, higher COPE-denial scores were significantly associated with lower odds of improvement in kinesiophobia (OR 0.43).

Patients with greater levels of problem-focused coping had significantly greater improvement in International Knee Documentation Committee (IKDC) scores, as did patients who were older and more active.

“Specific coping strategies appear to moderate the effect of pain perceptions on postoperative outcomes, with some coping strategies being protective and others being harmful,” the researchers said.

The findings were limited by several factors including the use of multiple comparisons, the inability to assess the impact of pain perception after knee rehabilitation independent of surgery, and the small number of some uncommon procedures, the researchers noted.

However, the results suggest that “recognition of pain perception and coping styles early on in treatment may help sports medicine providers identify patients at risk for an unsatisfactory subjective outcome,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Everhart JS et al. J Sci Med Sport. 2019. doi: 10.1016/j.jsams.2019.09.011.

Age-adjusted mortality from antineutrophil cytoplasmic autoantibody–associated vasculitides (AAV) in the United States declined by nearly 2% each year between 1999 and 2017, based on data from the Centers for Disease Control and Prevention.

Significant morbidity and mortality are associated with untreated AAV, wrote Alexander W. Steinberg, MD, of Saint Joseph Hospital, Denver, Colo., and colleagues.

“Although population data from the United Kingdom have shown decreased AAV-related mortality during the past 20 years, it is unknown whether this pattern has occurred in the United States,” they wrote.

In a study published in Annals of Internal Medicine, the researchers identified 11,316 AAV-related deaths from 1999 to 2017 in the CDC data.

Overall, age-adjusted mortality was 1.86 per 1,000,000 persons, with highest rates among non-Hispanic whites, men, and residents of the Midwest. Mortality from AAV declined by an average of 1.6% in each year of the study period, and changes in subgroups stratified by gender, race, and geographic region were similar.

Mortality increased with age and was highest among individuals aged 75-84 years, but a significant decline in mortality occurred among individuals aged 65-74 years. “The decrease in overall mortality and mortality among persons aged 65 to 74 years may reflect increased longevity due to improved treatment of AAV and common comorbid conditions,” the researchers said.

“Surprisingly, the authors found much lower age-adjusted mortality rates for non-Hispanic black persons (0.77) and moderately lower mortality rates for Hispanic persons (1.57) than for non-Hispanic white persons (2.03),” wrote John R. Stone, MD, PhD, of Creighton University, Omaha, Neb., in an accompanying editorial.

“Suppose the mortality rate differences reported by Steinberg and colleagues are statistically significant, accurately represent death certificate diagnoses, and match people’s racial/ethnic self-identification. The data then show neither that the vasculitides actually have lower mortality rates in blacks or Hispanics compared with whites, nor that the diseases are indeed less frequent in blacks and Hispanics,” he said. “Rather, these differences probably signify how social inequities, social structural violence, and inferior health care access adversely influence diagnosis of rare diseases and promote health inequity,” Dr. Stone added. The findings suggest that clinicians should remain alert to AAV in some ethnic groups to improve diagnostic accuracy, he said.

“Moreover, improved AAV diagnosis in such groups is key to recruiting participants for research investigating whether therapies should differ among populations,” he emphasized.

The study findings were limited by possible under- or overreporting of AAV on death certificates, but they were strengthened by the large sample size, the researchers noted. “We hope that the mortality patterns presented here can be used to direct future research on the driving forces behind these trends,” they said.

Dr. Steinberg had no financial conflicts to disclose. Dr. Stone had no financial conflicts to disclose.

SOURCES: Steinberg AW et al. Ann Intern Med. 2019 Oct 8. doi: 10.7326/M19-1564; and Stone JR. Ann Intern Med. 2019 Oct 8. doi: 10.7326/M19-2755.

Age-adjusted mortality from antineutrophil cytoplasmic autoantibody–associated vasculitides (AAV) in the United States declined by nearly 2% each year between 1999 and 2017, based on data from the Centers for Disease Control and Prevention.

Significant morbidity and mortality are associated with untreated AAV, wrote Alexander W. Steinberg, MD, of Saint Joseph Hospital, Denver, Colo., and colleagues.

“Although population data from the United Kingdom have shown decreased AAV-related mortality during the past 20 years, it is unknown whether this pattern has occurred in the United States,” they wrote.

In a study published in Annals of Internal Medicine, the researchers identified 11,316 AAV-related deaths from 1999 to 2017 in the CDC data.

Overall, age-adjusted mortality was 1.86 per 1,000,000 persons, with highest rates among non-Hispanic whites, men, and residents of the Midwest. Mortality from AAV declined by an average of 1.6% in each year of the study period, and changes in subgroups stratified by gender, race, and geographic region were similar.

Mortality increased with age and was highest among individuals aged 75-84 years, but a significant decline in mortality occurred among individuals aged 65-74 years. “The decrease in overall mortality and mortality among persons aged 65 to 74 years may reflect increased longevity due to improved treatment of AAV and common comorbid conditions,” the researchers said.

“Surprisingly, the authors found much lower age-adjusted mortality rates for non-Hispanic black persons (0.77) and moderately lower mortality rates for Hispanic persons (1.57) than for non-Hispanic white persons (2.03),” wrote John R. Stone, MD, PhD, of Creighton University, Omaha, Neb., in an accompanying editorial.

“Suppose the mortality rate differences reported by Steinberg and colleagues are statistically significant, accurately represent death certificate diagnoses, and match people’s racial/ethnic self-identification. The data then show neither that the vasculitides actually have lower mortality rates in blacks or Hispanics compared with whites, nor that the diseases are indeed less frequent in blacks and Hispanics,” he said. “Rather, these differences probably signify how social inequities, social structural violence, and inferior health care access adversely influence diagnosis of rare diseases and promote health inequity,” Dr. Stone added. The findings suggest that clinicians should remain alert to AAV in some ethnic groups to improve diagnostic accuracy, he said.

“Moreover, improved AAV diagnosis in such groups is key to recruiting participants for research investigating whether therapies should differ among populations,” he emphasized.

The study findings were limited by possible under- or overreporting of AAV on death certificates, but they were strengthened by the large sample size, the researchers noted. “We hope that the mortality patterns presented here can be used to direct future research on the driving forces behind these trends,” they said.

Dr. Steinberg had no financial conflicts to disclose. Dr. Stone had no financial conflicts to disclose.

SOURCES: Steinberg AW et al. Ann Intern Med. 2019 Oct 8. doi: 10.7326/M19-1564; and Stone JR. Ann Intern Med. 2019 Oct 8. doi: 10.7326/M19-2755.

Age-adjusted mortality from antineutrophil cytoplasmic autoantibody–associated vasculitides (AAV) in the United States declined by nearly 2% each year between 1999 and 2017, based on data from the Centers for Disease Control and Prevention.

Significant morbidity and mortality are associated with untreated AAV, wrote Alexander W. Steinberg, MD, of Saint Joseph Hospital, Denver, Colo., and colleagues.

“Although population data from the United Kingdom have shown decreased AAV-related mortality during the past 20 years, it is unknown whether this pattern has occurred in the United States,” they wrote.

In a study published in Annals of Internal Medicine, the researchers identified 11,316 AAV-related deaths from 1999 to 2017 in the CDC data.

Overall, age-adjusted mortality was 1.86 per 1,000,000 persons, with highest rates among non-Hispanic whites, men, and residents of the Midwest. Mortality from AAV declined by an average of 1.6% in each year of the study period, and changes in subgroups stratified by gender, race, and geographic region were similar.

Mortality increased with age and was highest among individuals aged 75-84 years, but a significant decline in mortality occurred among individuals aged 65-74 years. “The decrease in overall mortality and mortality among persons aged 65 to 74 years may reflect increased longevity due to improved treatment of AAV and common comorbid conditions,” the researchers said.

“Surprisingly, the authors found much lower age-adjusted mortality rates for non-Hispanic black persons (0.77) and moderately lower mortality rates for Hispanic persons (1.57) than for non-Hispanic white persons (2.03),” wrote John R. Stone, MD, PhD, of Creighton University, Omaha, Neb., in an accompanying editorial.

“Suppose the mortality rate differences reported by Steinberg and colleagues are statistically significant, accurately represent death certificate diagnoses, and match people’s racial/ethnic self-identification. The data then show neither that the vasculitides actually have lower mortality rates in blacks or Hispanics compared with whites, nor that the diseases are indeed less frequent in blacks and Hispanics,” he said. “Rather, these differences probably signify how social inequities, social structural violence, and inferior health care access adversely influence diagnosis of rare diseases and promote health inequity,” Dr. Stone added. The findings suggest that clinicians should remain alert to AAV in some ethnic groups to improve diagnostic accuracy, he said.

“Moreover, improved AAV diagnosis in such groups is key to recruiting participants for research investigating whether therapies should differ among populations,” he emphasized.

The study findings were limited by possible under- or overreporting of AAV on death certificates, but they were strengthened by the large sample size, the researchers noted. “We hope that the mortality patterns presented here can be used to direct future research on the driving forces behind these trends,” they said.

Dr. Steinberg had no financial conflicts to disclose. Dr. Stone had no financial conflicts to disclose.

SOURCES: Steinberg AW et al. Ann Intern Med. 2019 Oct 8. doi: 10.7326/M19-1564; and Stone JR. Ann Intern Med. 2019 Oct 8. doi: 10.7326/M19-2755.

Burnout among health care professionals has been associated with lower quality of care, but the effect may be smaller than it seems, based on data from a meta-analysis of more than 200,000 clinicians.

Previous studies have reported associations between burnout and lower quality of care, but a standardized approach to analyze bias in the studies is lacking, wrote Daniel S. Tawfik, MD, of Stanford (Calif.) University and colleagues.

In a study published in the Annals of Internal Medicine, the researchers identified 123 publications from 1994 to 2019 with 142 study populations that included 241,553 health care providers.

Emotional exhaustion was the primary predictor for lower quality of care in 75 study populations, and overall burnout and depersonalization were the primary predictors for 56 and 11 study populations, respectively.

In an analysis of 114 unique burnout-quality combinations, 58 showed effects of burnout related to poor-quality care, 6 showed burnout related to high-quality care, and 50 showed no significant effect. Approximately one-third (33%) of the burnout-quality combinations were reported at least three times. In a review of the 46 burnout-quality combinations with primary effect sizes, 24 showed a significant effect of burnout on poor quality of care, 1 showed a significant effect of burnout on high quality of care, and 21 showed no significant effect.

The researchers also tested study bias using the Ioannidis test and found “an excess of observed versus predicted statistically significant studies (73% observed vs. 62%).”

The findings were limited by several factors, including the use of many cross-sectional, observational studies that could not show causality, the researchers noted. However, the results suggest several implications for future research including the need to consider exaggerated effects and reduce bias.

“Although the effect sizes in the published literature are modestly strong, our finding of excess significance implies that the true magnitude may be smaller than reported, and the studies that attempted to lower the risk of bias demonstrate fewer significant associations than the full evidence base,” the researchers noted.

“Whether curtailing burnout improves quality of care, or whether improving quality of care reduces burnout, is not yet known, and adequately powered and designed randomized trials will be indispensable in answering these questions,” they concluded.

The study was supported by the Stanford Maternal and Child Health Research Institute. Dr. Tawfik disclosed grants from Stanford Maternal and Child Health Research Institute during the study period.

SOURCE: Tawfik DS et al. Ann Intern Med. 2019 Oct 8. doi: 10.7326/M19-1152.

Burnout among health care professionals has been associated with lower quality of care, but the effect may be smaller than it seems, based on data from a meta-analysis of more than 200,000 clinicians.

Previous studies have reported associations between burnout and lower quality of care, but a standardized approach to analyze bias in the studies is lacking, wrote Daniel S. Tawfik, MD, of Stanford (Calif.) University and colleagues.

In a study published in the Annals of Internal Medicine, the researchers identified 123 publications from 1994 to 2019 with 142 study populations that included 241,553 health care providers.

Emotional exhaustion was the primary predictor for lower quality of care in 75 study populations, and overall burnout and depersonalization were the primary predictors for 56 and 11 study populations, respectively.

In an analysis of 114 unique burnout-quality combinations, 58 showed effects of burnout related to poor-quality care, 6 showed burnout related to high-quality care, and 50 showed no significant effect. Approximately one-third (33%) of the burnout-quality combinations were reported at least three times. In a review of the 46 burnout-quality combinations with primary effect sizes, 24 showed a significant effect of burnout on poor quality of care, 1 showed a significant effect of burnout on high quality of care, and 21 showed no significant effect.

The researchers also tested study bias using the Ioannidis test and found “an excess of observed versus predicted statistically significant studies (73% observed vs. 62%).”

The findings were limited by several factors, including the use of many cross-sectional, observational studies that could not show causality, the researchers noted. However, the results suggest several implications for future research including the need to consider exaggerated effects and reduce bias.

“Although the effect sizes in the published literature are modestly strong, our finding of excess significance implies that the true magnitude may be smaller than reported, and the studies that attempted to lower the risk of bias demonstrate fewer significant associations than the full evidence base,” the researchers noted.

“Whether curtailing burnout improves quality of care, or whether improving quality of care reduces burnout, is not yet known, and adequately powered and designed randomized trials will be indispensable in answering these questions,” they concluded.

The study was supported by the Stanford Maternal and Child Health Research Institute. Dr. Tawfik disclosed grants from Stanford Maternal and Child Health Research Institute during the study period.

SOURCE: Tawfik DS et al. Ann Intern Med. 2019 Oct 8. doi: 10.7326/M19-1152.

Burnout among health care professionals has been associated with lower quality of care, but the effect may be smaller than it seems, based on data from a meta-analysis of more than 200,000 clinicians.

Previous studies have reported associations between burnout and lower quality of care, but a standardized approach to analyze bias in the studies is lacking, wrote Daniel S. Tawfik, MD, of Stanford (Calif.) University and colleagues.

In a study published in the Annals of Internal Medicine, the researchers identified 123 publications from 1994 to 2019 with 142 study populations that included 241,553 health care providers.

Emotional exhaustion was the primary predictor for lower quality of care in 75 study populations, and overall burnout and depersonalization were the primary predictors for 56 and 11 study populations, respectively.

In an analysis of 114 unique burnout-quality combinations, 58 showed effects of burnout related to poor-quality care, 6 showed burnout related to high-quality care, and 50 showed no significant effect. Approximately one-third (33%) of the burnout-quality combinations were reported at least three times. In a review of the 46 burnout-quality combinations with primary effect sizes, 24 showed a significant effect of burnout on poor quality of care, 1 showed a significant effect of burnout on high quality of care, and 21 showed no significant effect.

The researchers also tested study bias using the Ioannidis test and found “an excess of observed versus predicted statistically significant studies (73% observed vs. 62%).”

The findings were limited by several factors, including the use of many cross-sectional, observational studies that could not show causality, the researchers noted. However, the results suggest several implications for future research including the need to consider exaggerated effects and reduce bias.

“Although the effect sizes in the published literature are modestly strong, our finding of excess significance implies that the true magnitude may be smaller than reported, and the studies that attempted to lower the risk of bias demonstrate fewer significant associations than the full evidence base,” the researchers noted.

“Whether curtailing burnout improves quality of care, or whether improving quality of care reduces burnout, is not yet known, and adequately powered and designed randomized trials will be indispensable in answering these questions,” they concluded.

The study was supported by the Stanford Maternal and Child Health Research Institute. Dr. Tawfik disclosed grants from Stanford Maternal and Child Health Research Institute during the study period.

SOURCE: Tawfik DS et al. Ann Intern Med. 2019 Oct 8. doi: 10.7326/M19-1152.

The Food and Drug Administration has approved trifarotene cream 0.005% for the treatment of acne vulgaris. The product is manufactured by Galderma under the brand name Aklief.

Olivier Le Moal/Getty Images

The approval was based on data from a pair of phase 3, randomized trials including 2,420 patients aged 9 years and older. The trials evaluated the effectiveness of the cream in a once-daily topical dose for facial and truncal acne at 12 weeks. Patients showed a significant reduction in the number of inflammatory lesions as early as 2 weeks on the face (including forehead cheeks, nose, and chin) and as early as 4 weeks on the trunk (including back, chest, and shoulders), compared with a control cream. The most common treatment-emergent adverse events were pain, dryness, discoloration, or rash at the site of application. Some patients also reported sunburn.

The complete study findings were published in the June issue of the Journal of the American Academy of Dermatology.

The studies, funded by Galderma, “showed that once-daily trifarotene cream appears effective and safe, with manageable local tolerability, for the treatment for facial and truncal acne,” wrote lead author Jerry Tan, MD, of the University of Western Ontario, London, and colleagues. “The studies provide substantial evidence to support use of this new topical retinoid in facial and truncal acne,” the researchers wrote.

Trifarotene is designed to target the retinoic acid receptor gamma, the most common retinoic acid receptor in the skin, and is the first new retinoid to be approved by the FDA in approximately 2 decades, according to a press release from Galderma.

The product is expected to be available in the United States in November 2019 in a 45-g pump.

The Food and Drug Administration has approved trifarotene cream 0.005% for the treatment of acne vulgaris. The product is manufactured by Galderma under the brand name Aklief.

Olivier Le Moal/Getty Images

The approval was based on data from a pair of phase 3, randomized trials including 2,420 patients aged 9 years and older. The trials evaluated the effectiveness of the cream in a once-daily topical dose for facial and truncal acne at 12 weeks. Patients showed a significant reduction in the number of inflammatory lesions as early as 2 weeks on the face (including forehead cheeks, nose, and chin) and as early as 4 weeks on the trunk (including back, chest, and shoulders), compared with a control cream. The most common treatment-emergent adverse events were pain, dryness, discoloration, or rash at the site of application. Some patients also reported sunburn.

The complete study findings were published in the June issue of the Journal of the American Academy of Dermatology.

The studies, funded by Galderma, “showed that once-daily trifarotene cream appears effective and safe, with manageable local tolerability, for the treatment for facial and truncal acne,” wrote lead author Jerry Tan, MD, of the University of Western Ontario, London, and colleagues. “The studies provide substantial evidence to support use of this new topical retinoid in facial and truncal acne,” the researchers wrote.

Trifarotene is designed to target the retinoic acid receptor gamma, the most common retinoic acid receptor in the skin, and is the first new retinoid to be approved by the FDA in approximately 2 decades, according to a press release from Galderma.

The product is expected to be available in the United States in November 2019 in a 45-g pump.

The Food and Drug Administration has approved trifarotene cream 0.005% for the treatment of acne vulgaris. The product is manufactured by Galderma under the brand name Aklief.

Olivier Le Moal/Getty Images

The approval was based on data from a pair of phase 3, randomized trials including 2,420 patients aged 9 years and older. The trials evaluated the effectiveness of the cream in a once-daily topical dose for facial and truncal acne at 12 weeks. Patients showed a significant reduction in the number of inflammatory lesions as early as 2 weeks on the face (including forehead cheeks, nose, and chin) and as early as 4 weeks on the trunk (including back, chest, and shoulders), compared with a control cream. The most common treatment-emergent adverse events were pain, dryness, discoloration, or rash at the site of application. Some patients also reported sunburn.

The complete study findings were published in the June issue of the Journal of the American Academy of Dermatology.

The studies, funded by Galderma, “showed that once-daily trifarotene cream appears effective and safe, with manageable local tolerability, for the treatment for facial and truncal acne,” wrote lead author Jerry Tan, MD, of the University of Western Ontario, London, and colleagues. “The studies provide substantial evidence to support use of this new topical retinoid in facial and truncal acne,” the researchers wrote.

Trifarotene is designed to target the retinoic acid receptor gamma, the most common retinoic acid receptor in the skin, and is the first new retinoid to be approved by the FDA in approximately 2 decades, according to a press release from Galderma.

The product is expected to be available in the United States in November 2019 in a 45-g pump.

Women who accumulated more indoor tanning sessions over time significantly increased their risk for squamous cell cancer over women who never engaged in indoor tanning, based on data from 159,419 women.

Previous research has examined associations between indoor tanning and cutaneous melanoma, but an association between indoor tanning and squamous cell carcinoma (SCC) has not been well studied, wrote Simon Lergenmuller, MSc, of the University of Oslo, and colleagues.

In a prospective cohort study published in JAMA Dermatology, the researchers surveyed 159,419 women from the Norwegian Women and Cancer study. Of these, 95,552 women (69%) reported ever use of indoor tanning. The average age at study inclusion was 50 years. During an average of 17 years’ follow-up, 597 women developed SCC.

Overall, the risk of SCC increased with increasing numbers of indoor tanning sessions. The adjusted hazard ratio for most tanning sessions versus no tanning sessions was 1.83. “The association between cumulative exposure to indoor tanning and SCC risk was the same regardless of duration of use and age at initiation,” the researchers wrote.

The risk of SCC was significantly higher both among women with 10 years or less of tanning bed use and among those with more than 10 years of use, compared with never users (HRs, 1.41 and 1.43, respectively). Similarly, researchers found a significantly higher risk of SCC among women who started indoor tanning at age 30 years or older and those who started younger than 30 years, compared with never users (HRs, 1.36 and HR, 1.51, respectively).

No significant association appeared between age at initiation of indoor tanning and age at the time of SCC diagnosis.

The study findings were limited by several factors including the variation in UV radiation among tanning devices, the lack of data on men, and the retrospective collection of UV exposure data that likely led to some misclassification, the researchers noted.

However, the results were strengthened by the large sample size and support the association between increased exposure to indoor tanning and increased risk of SCC, they wrote. “Avoidance of indoor tanning may help prevent not only melanoma but also SCC, and our results support the development of policies that regulate indoor tanning.”

The study was supported by the Institute of Basic Medical Sciences, University of Oslo, and the Norwegian Cancer Society. The researchers had no financial conflicts to disclose.

SOURCE: Lergenmuller S et al. JAMA Dermatol. 2019 Oct 2. doi: 10.1001/jamadermatol.2019.2681.

Women who accumulated more indoor tanning sessions over time significantly increased their risk for squamous cell cancer over women who never engaged in indoor tanning, based on data from 159,419 women.

Previous research has examined associations between indoor tanning and cutaneous melanoma, but an association between indoor tanning and squamous cell carcinoma (SCC) has not been well studied, wrote Simon Lergenmuller, MSc, of the University of Oslo, and colleagues.

In a prospective cohort study published in JAMA Dermatology, the researchers surveyed 159,419 women from the Norwegian Women and Cancer study. Of these, 95,552 women (69%) reported ever use of indoor tanning. The average age at study inclusion was 50 years. During an average of 17 years’ follow-up, 597 women developed SCC.

Overall, the risk of SCC increased with increasing numbers of indoor tanning sessions. The adjusted hazard ratio for most tanning sessions versus no tanning sessions was 1.83. “The association between cumulative exposure to indoor tanning and SCC risk was the same regardless of duration of use and age at initiation,” the researchers wrote.

The risk of SCC was significantly higher both among women with 10 years or less of tanning bed use and among those with more than 10 years of use, compared with never users (HRs, 1.41 and 1.43, respectively). Similarly, researchers found a significantly higher risk of SCC among women who started indoor tanning at age 30 years or older and those who started younger than 30 years, compared with never users (HRs, 1.36 and HR, 1.51, respectively).

No significant association appeared between age at initiation of indoor tanning and age at the time of SCC diagnosis.

The study findings were limited by several factors including the variation in UV radiation among tanning devices, the lack of data on men, and the retrospective collection of UV exposure data that likely led to some misclassification, the researchers noted.

However, the results were strengthened by the large sample size and support the association between increased exposure to indoor tanning and increased risk of SCC, they wrote. “Avoidance of indoor tanning may help prevent not only melanoma but also SCC, and our results support the development of policies that regulate indoor tanning.”

The study was supported by the Institute of Basic Medical Sciences, University of Oslo, and the Norwegian Cancer Society. The researchers had no financial conflicts to disclose.

SOURCE: Lergenmuller S et al. JAMA Dermatol. 2019 Oct 2. doi: 10.1001/jamadermatol.2019.2681.

Women who accumulated more indoor tanning sessions over time significantly increased their risk for squamous cell cancer over women who never engaged in indoor tanning, based on data from 159,419 women.

Previous research has examined associations between indoor tanning and cutaneous melanoma, but an association between indoor tanning and squamous cell carcinoma (SCC) has not been well studied, wrote Simon Lergenmuller, MSc, of the University of Oslo, and colleagues.

In a prospective cohort study published in JAMA Dermatology, the researchers surveyed 159,419 women from the Norwegian Women and Cancer study. Of these, 95,552 women (69%) reported ever use of indoor tanning. The average age at study inclusion was 50 years. During an average of 17 years’ follow-up, 597 women developed SCC.

Overall, the risk of SCC increased with increasing numbers of indoor tanning sessions. The adjusted hazard ratio for most tanning sessions versus no tanning sessions was 1.83. “The association between cumulative exposure to indoor tanning and SCC risk was the same regardless of duration of use and age at initiation,” the researchers wrote.

The risk of SCC was significantly higher both among women with 10 years or less of tanning bed use and among those with more than 10 years of use, compared with never users (HRs, 1.41 and 1.43, respectively). Similarly, researchers found a significantly higher risk of SCC among women who started indoor tanning at age 30 years or older and those who started younger than 30 years, compared with never users (HRs, 1.36 and HR, 1.51, respectively).

No significant association appeared between age at initiation of indoor tanning and age at the time of SCC diagnosis.

The study findings were limited by several factors including the variation in UV radiation among tanning devices, the lack of data on men, and the retrospective collection of UV exposure data that likely led to some misclassification, the researchers noted.

However, the results were strengthened by the large sample size and support the association between increased exposure to indoor tanning and increased risk of SCC, they wrote. “Avoidance of indoor tanning may help prevent not only melanoma but also SCC, and our results support the development of policies that regulate indoor tanning.”

The study was supported by the Institute of Basic Medical Sciences, University of Oslo, and the Norwegian Cancer Society. The researchers had no financial conflicts to disclose.

SOURCE: Lergenmuller S et al. JAMA Dermatol. 2019 Oct 2. doi: 10.1001/jamadermatol.2019.2681.

Sleeping supine during late pregnancy was independently associated with lower birth weight, but the number of women in this subgroup was small in the study.

Data from previous studies suggest that impaired uteroplacental flow can affect fetal growth, wrote Ngaire H. Anderson, PhD, of the University of Auckland, N.Z., and colleagues.

“The initial going-to-sleep position is the sleep position that women maintain for the longest duration throughout the night; therefore, going-to-sleep position is likely to have the greatest impact on blood flow to the developing fetus,” they said.

In a study published in JAMA Network Open, the researchers interviewed women with ongoing pregnancies at 28 weeks’ gestation or later to determine their sleeping positions. The mean age of the participants was 30 years. Of the 1,760 women, 3% reported that they usually slept supine during the past 1-4 weeks.

The adjusted mean birth weight was 3,410 g among supine sleepers and 3,554 g among nonsupine sleepers. The primary outcome was an adjusted mean difference in birth weight between infants of supine sleepers and nonsupine sleepers, which was a statistically significant 144 g (P = .009).

The study findings were limited by several factors including the small number of women who were reported supine sleepers, as well as the reliance on self-reports of sleep position, the researchers said.

However, women who had going-to-sleep data for the previous night and the previous month suggest that most women are consistent in their going-to-sleep position, they noted. “It is also biologically plausible that the association of decreased maternal blood flow on birth size with supine maternal position is cumulative over time,” but the researchers were not able to investigate how the duration of supine sleeping might further affect birth weight.

Although it might make additional studies more difficult, a public health campaign to encourage pregnant women to sleep on their side during the third trimester is a safe and easy opportunity to potentially optimize birth weight, they added.

The study was important because of the limited number of high-quality studies on the effects of maternal sleep on perinatal outcomes, Martina Badell, MD of Emory University in Atlanta said in an interview.

“The overall findings suggested a possible small increased risk of small-for-gestational-age babies with supine maternal sleeping, however, the absolute gram difference of 144 grams at term may not be clinically relevant,” she said. In addition, the relatively small number of women who reported supine sleep in late pregnancy suggests that broad public health campaigns or recommendations may not be indicated at this time.

“Also, the percentage of women who are supine sleepers at term is only approximately 3%, and this study didn’t assess reasons for supine sleeping in this small subset of women,” she said. “Further research is needed to assess whether there are specific maternal factors associated with supine sleeping, such as GI symptoms or respiratory difficulties, which could contribute to smaller fetal size rather than the sleep position itself.”

The study was supported by a Trans-Tasman Research Funding Grant by Cure Kids and Red Nose Australia. Six coauthors reported receiving numerous grants from a variety of organizations. Dr. Anderson and the remaining coauthors had no financial conflicts to disclose. Dr. Badell had no relevant financial disclosures.

SOURCE: Anderson NH et al. JAMA Network Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.12614.

Sleeping supine during late pregnancy was independently associated with lower birth weight, but the number of women in this subgroup was small in the study.

Data from previous studies suggest that impaired uteroplacental flow can affect fetal growth, wrote Ngaire H. Anderson, PhD, of the University of Auckland, N.Z., and colleagues.

“The initial going-to-sleep position is the sleep position that women maintain for the longest duration throughout the night; therefore, going-to-sleep position is likely to have the greatest impact on blood flow to the developing fetus,” they said.

In a study published in JAMA Network Open, the researchers interviewed women with ongoing pregnancies at 28 weeks’ gestation or later to determine their sleeping positions. The mean age of the participants was 30 years. Of the 1,760 women, 3% reported that they usually slept supine during the past 1-4 weeks.

The adjusted mean birth weight was 3,410 g among supine sleepers and 3,554 g among nonsupine sleepers. The primary outcome was an adjusted mean difference in birth weight between infants of supine sleepers and nonsupine sleepers, which was a statistically significant 144 g (P = .009).

The study findings were limited by several factors including the small number of women who were reported supine sleepers, as well as the reliance on self-reports of sleep position, the researchers said.

However, women who had going-to-sleep data for the previous night and the previous month suggest that most women are consistent in their going-to-sleep position, they noted. “It is also biologically plausible that the association of decreased maternal blood flow on birth size with supine maternal position is cumulative over time,” but the researchers were not able to investigate how the duration of supine sleeping might further affect birth weight.

Although it might make additional studies more difficult, a public health campaign to encourage pregnant women to sleep on their side during the third trimester is a safe and easy opportunity to potentially optimize birth weight, they added.

The study was important because of the limited number of high-quality studies on the effects of maternal sleep on perinatal outcomes, Martina Badell, MD of Emory University in Atlanta said in an interview.

“The overall findings suggested a possible small increased risk of small-for-gestational-age babies with supine maternal sleeping, however, the absolute gram difference of 144 grams at term may not be clinically relevant,” she said. In addition, the relatively small number of women who reported supine sleep in late pregnancy suggests that broad public health campaigns or recommendations may not be indicated at this time.

“Also, the percentage of women who are supine sleepers at term is only approximately 3%, and this study didn’t assess reasons for supine sleeping in this small subset of women,” she said. “Further research is needed to assess whether there are specific maternal factors associated with supine sleeping, such as GI symptoms or respiratory difficulties, which could contribute to smaller fetal size rather than the sleep position itself.”

The study was supported by a Trans-Tasman Research Funding Grant by Cure Kids and Red Nose Australia. Six coauthors reported receiving numerous grants from a variety of organizations. Dr. Anderson and the remaining coauthors had no financial conflicts to disclose. Dr. Badell had no relevant financial disclosures.

SOURCE: Anderson NH et al. JAMA Network Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.12614.

Sleeping supine during late pregnancy was independently associated with lower birth weight, but the number of women in this subgroup was small in the study.

Data from previous studies suggest that impaired uteroplacental flow can affect fetal growth, wrote Ngaire H. Anderson, PhD, of the University of Auckland, N.Z., and colleagues.

“The initial going-to-sleep position is the sleep position that women maintain for the longest duration throughout the night; therefore, going-to-sleep position is likely to have the greatest impact on blood flow to the developing fetus,” they said.

In a study published in JAMA Network Open, the researchers interviewed women with ongoing pregnancies at 28 weeks’ gestation or later to determine their sleeping positions. The mean age of the participants was 30 years. Of the 1,760 women, 3% reported that they usually slept supine during the past 1-4 weeks.

The adjusted mean birth weight was 3,410 g among supine sleepers and 3,554 g among nonsupine sleepers. The primary outcome was an adjusted mean difference in birth weight between infants of supine sleepers and nonsupine sleepers, which was a statistically significant 144 g (P = .009).

The study findings were limited by several factors including the small number of women who were reported supine sleepers, as well as the reliance on self-reports of sleep position, the researchers said.

However, women who had going-to-sleep data for the previous night and the previous month suggest that most women are consistent in their going-to-sleep position, they noted. “It is also biologically plausible that the association of decreased maternal blood flow on birth size with supine maternal position is cumulative over time,” but the researchers were not able to investigate how the duration of supine sleeping might further affect birth weight.

Although it might make additional studies more difficult, a public health campaign to encourage pregnant women to sleep on their side during the third trimester is a safe and easy opportunity to potentially optimize birth weight, they added.

The study was important because of the limited number of high-quality studies on the effects of maternal sleep on perinatal outcomes, Martina Badell, MD of Emory University in Atlanta said in an interview.

“The overall findings suggested a possible small increased risk of small-for-gestational-age babies with supine maternal sleeping, however, the absolute gram difference of 144 grams at term may not be clinically relevant,” she said. In addition, the relatively small number of women who reported supine sleep in late pregnancy suggests that broad public health campaigns or recommendations may not be indicated at this time.

“Also, the percentage of women who are supine sleepers at term is only approximately 3%, and this study didn’t assess reasons for supine sleeping in this small subset of women,” she said. “Further research is needed to assess whether there are specific maternal factors associated with supine sleeping, such as GI symptoms or respiratory difficulties, which could contribute to smaller fetal size rather than the sleep position itself.”

The study was supported by a Trans-Tasman Research Funding Grant by Cure Kids and Red Nose Australia. Six coauthors reported receiving numerous grants from a variety of organizations. Dr. Anderson and the remaining coauthors had no financial conflicts to disclose. Dr. Badell had no relevant financial disclosures.

SOURCE: Anderson NH et al. JAMA Network Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.12614.

Persistent high rates of bacterial resistance to current treatments have created the need for more options, especially for the treatment of community-acquired bacterial pneumonia (CABP), which remains a leading cause of hospitalization and death in the United States, wrote Elizabeth Alexander, MD, of Nabriva Therapeutics in King of Prussia, Penn., and colleagues. Lefamulin, “the first pleuromutilin antibiotic approved for intravenous and oral use in humans,” has demonstrated activity against many CABP-causing pathogens, including some not susceptible to other classes of antimicrobials, they noted.

Findings of Lefamulin Evaluation Against Pneumonia 2 (LEAP2) were published in JAMA. In this study, the researchers randomized 370 patients to 600 mg of oral lefamulin every 12 hours for 5 days and 368 patients to 400 mg of oral moxifloxacin every 24 hours for 7 days.

Early clinical response rates at 96 hours were 90.8% for both medications (difference of 0.1%). In addition, the rates of clinical response success were similar between the groups in both the modified intent-to-treat population (87.5% with lefamulin and 89.1% with moxifloxacin) and the clinically evaluable population (89.7% with lefamulin and 93.6% with moxifloxacin).

Gastrointestinal issues of diarrhea and nausea were the two most frequently reported treatment-emergent adverse events in both groups. Both conditions occurred more often in the lefamulin group, compared with the moxifloxacin group, but the differences were not significant (12.2% vs. 1.1% and 5.2% vs. 1.9%, respectively).

The study findings were limited by several factors including strict exclusion criteria that may limit the generalizability of the results, as well as a lack of testing for viral copathogens, low recovery of resistant pathogens, and possible misclassification of patient ethnicity, the researchers noted.

However, the results were strengthened by the randomized design, inclusion of patients with more severe CABP, and low rate of discontinuation, they said. The data support previous studies of lefamulin. Its lack of cross-resistance to other drug classes, coverage of typical and atypical CABP pathogens, and options for both oral and intravenous use suggest that it “may provide an alternative approach for the treatment of vulnerable patients,” the researchers said.

The study was supported by Nabriva Therapeutics. Dr. Alexander and several coauthors are employees of Nabriva Therapeutics and own stock in the company.

SOURCE: Alexander E et al. JAMA. 2019 Sep 27. doi:10.1001/jama.2019.15468.

Persistent high rates of bacterial resistance to current treatments have created the need for more options, especially for the treatment of community-acquired bacterial pneumonia (CABP), which remains a leading cause of hospitalization and death in the United States, wrote Elizabeth Alexander, MD, of Nabriva Therapeutics in King of Prussia, Penn., and colleagues. Lefamulin, “the first pleuromutilin antibiotic approved for intravenous and oral use in humans,” has demonstrated activity against many CABP-causing pathogens, including some not susceptible to other classes of antimicrobials, they noted.

Findings of Lefamulin Evaluation Against Pneumonia 2 (LEAP2) were published in JAMA. In this study, the researchers randomized 370 patients to 600 mg of oral lefamulin every 12 hours for 5 days and 368 patients to 400 mg of oral moxifloxacin every 24 hours for 7 days.

Early clinical response rates at 96 hours were 90.8% for both medications (difference of 0.1%). In addition, the rates of clinical response success were similar between the groups in both the modified intent-to-treat population (87.5% with lefamulin and 89.1% with moxifloxacin) and the clinically evaluable population (89.7% with lefamulin and 93.6% with moxifloxacin).

Gastrointestinal issues of diarrhea and nausea were the two most frequently reported treatment-emergent adverse events in both groups. Both conditions occurred more often in the lefamulin group, compared with the moxifloxacin group, but the differences were not significant (12.2% vs. 1.1% and 5.2% vs. 1.9%, respectively).

The study findings were limited by several factors including strict exclusion criteria that may limit the generalizability of the results, as well as a lack of testing for viral copathogens, low recovery of resistant pathogens, and possible misclassification of patient ethnicity, the researchers noted.

However, the results were strengthened by the randomized design, inclusion of patients with more severe CABP, and low rate of discontinuation, they said. The data support previous studies of lefamulin. Its lack of cross-resistance to other drug classes, coverage of typical and atypical CABP pathogens, and options for both oral and intravenous use suggest that it “may provide an alternative approach for the treatment of vulnerable patients,” the researchers said.

The study was supported by Nabriva Therapeutics. Dr. Alexander and several coauthors are employees of Nabriva Therapeutics and own stock in the company.

SOURCE: Alexander E et al. JAMA. 2019 Sep 27. doi:10.1001/jama.2019.15468.

Persistent high rates of bacterial resistance to current treatments have created the need for more options, especially for the treatment of community-acquired bacterial pneumonia (CABP), which remains a leading cause of hospitalization and death in the United States, wrote Elizabeth Alexander, MD, of Nabriva Therapeutics in King of Prussia, Penn., and colleagues. Lefamulin, “the first pleuromutilin antibiotic approved for intravenous and oral use in humans,” has demonstrated activity against many CABP-causing pathogens, including some not susceptible to other classes of antimicrobials, they noted.

Findings of Lefamulin Evaluation Against Pneumonia 2 (LEAP2) were published in JAMA. In this study, the researchers randomized 370 patients to 600 mg of oral lefamulin every 12 hours for 5 days and 368 patients to 400 mg of oral moxifloxacin every 24 hours for 7 days.

Early clinical response rates at 96 hours were 90.8% for both medications (difference of 0.1%). In addition, the rates of clinical response success were similar between the groups in both the modified intent-to-treat population (87.5% with lefamulin and 89.1% with moxifloxacin) and the clinically evaluable population (89.7% with lefamulin and 93.6% with moxifloxacin).

Gastrointestinal issues of diarrhea and nausea were the two most frequently reported treatment-emergent adverse events in both groups. Both conditions occurred more often in the lefamulin group, compared with the moxifloxacin group, but the differences were not significant (12.2% vs. 1.1% and 5.2% vs. 1.9%, respectively).

The study findings were limited by several factors including strict exclusion criteria that may limit the generalizability of the results, as well as a lack of testing for viral copathogens, low recovery of resistant pathogens, and possible misclassification of patient ethnicity, the researchers noted.

However, the results were strengthened by the randomized design, inclusion of patients with more severe CABP, and low rate of discontinuation, they said. The data support previous studies of lefamulin. Its lack of cross-resistance to other drug classes, coverage of typical and atypical CABP pathogens, and options for both oral and intravenous use suggest that it “may provide an alternative approach for the treatment of vulnerable patients,” the researchers said.

The study was supported by Nabriva Therapeutics. Dr. Alexander and several coauthors are employees of Nabriva Therapeutics and own stock in the company.

SOURCE: Alexander E et al. JAMA. 2019 Sep 27. doi:10.1001/jama.2019.15468.

At least 50% of patients with irritable bowel syndrome (IBS) described their condition as “extremely bothersome” based on survey data from 3,254 individuals. However, differences in the nature of other symptoms among IBS subtypes, namely IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C), have not been well studied, wrote Sarah Ballou, PhD, of Beth Israel Deaconess Medical Center, Boston, and colleagues.

Source: American Gastroenterological Association

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed survey results from 1,587 individuals with IBS-D and 1,667 with IBS-C. The average age of the patients was 47 years, 81% were female, and 90% were white.

Approximately 84% of patients with IBS-C and 93% of those with IBS-D reported abdominal pain, the most common symptom in both groups. Overall, 36% of the 1,885 patients employed or in school reported decreased productivity in those settings.

IBS-C patients were significantly more likely to report that their symptoms caused them to avoid sex, feel self-conscious about their bodies, have trouble concentrating, and feel “not like myself,” compared with IBS-D patients (P less than .004 for all).

IBS-D patients were significantly more likely to report that their symptoms caused them to avoid traveling in general, avoid places without bathrooms, avoid leaving the house, and have trouble making plans, compared with IBS-C patients (P less than .004 for all).

The survey also asked respondents what they would give up for 1 month in exchange for 1 month of relief from IBS symptoms. Overall, approximately 60% said they would give up alcohol, 55% said they would give up caffeine, 40% would give up sex, 24.5% would give up their cell phones, and 21.5% would give up the internet, the researchers wrote.

The study findings were limited by several factors, including the absence of survey respondents with mixed-type IBS, the reliance on self-reports, and the potential for recall bias. Also, the study was not designed to assess the impact of other comorbidities and did not include non-IBS controls, the researchers noted.

However, the results suggest that patients with different IBS subtypes struggle differently in areas of daily function, which has implications for treatment, they wrote.

“This study highlights important differences between IBS-C and IBS-D, which could impact the development and refinement of mind-body therapies for IBS, with tailored treatment goals for each IBS subtype. For example, treatment tailored specifically for IBS-D may be more behaviorally focused (e.g., exposure to specific situations outside the home) while treatment for IBS-C may be more cognitively focused (e.g., evaluating self-esteem and beliefs about self and others) in addition to targeting the bowel dysfunction and pain,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Ballou S et al. Clin Gastroenterol Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.016.

At least 50% of patients with irritable bowel syndrome (IBS) described their condition as “extremely bothersome” based on survey data from 3,254 individuals. However, differences in the nature of other symptoms among IBS subtypes, namely IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C), have not been well studied, wrote Sarah Ballou, PhD, of Beth Israel Deaconess Medical Center, Boston, and colleagues.

Source: American Gastroenterological Association

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed survey results from 1,587 individuals with IBS-D and 1,667 with IBS-C. The average age of the patients was 47 years, 81% were female, and 90% were white.

Approximately 84% of patients with IBS-C and 93% of those with IBS-D reported abdominal pain, the most common symptom in both groups. Overall, 36% of the 1,885 patients employed or in school reported decreased productivity in those settings.

IBS-C patients were significantly more likely to report that their symptoms caused them to avoid sex, feel self-conscious about their bodies, have trouble concentrating, and feel “not like myself,” compared with IBS-D patients (P less than .004 for all).

IBS-D patients were significantly more likely to report that their symptoms caused them to avoid traveling in general, avoid places without bathrooms, avoid leaving the house, and have trouble making plans, compared with IBS-C patients (P less than .004 for all).

The survey also asked respondents what they would give up for 1 month in exchange for 1 month of relief from IBS symptoms. Overall, approximately 60% said they would give up alcohol, 55% said they would give up caffeine, 40% would give up sex, 24.5% would give up their cell phones, and 21.5% would give up the internet, the researchers wrote.

The study findings were limited by several factors, including the absence of survey respondents with mixed-type IBS, the reliance on self-reports, and the potential for recall bias. Also, the study was not designed to assess the impact of other comorbidities and did not include non-IBS controls, the researchers noted.

However, the results suggest that patients with different IBS subtypes struggle differently in areas of daily function, which has implications for treatment, they wrote.

“This study highlights important differences between IBS-C and IBS-D, which could impact the development and refinement of mind-body therapies for IBS, with tailored treatment goals for each IBS subtype. For example, treatment tailored specifically for IBS-D may be more behaviorally focused (e.g., exposure to specific situations outside the home) while treatment for IBS-C may be more cognitively focused (e.g., evaluating self-esteem and beliefs about self and others) in addition to targeting the bowel dysfunction and pain,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Ballou S et al. Clin Gastroenterol Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.016.

At least 50% of patients with irritable bowel syndrome (IBS) described their condition as “extremely bothersome” based on survey data from 3,254 individuals. However, differences in the nature of other symptoms among IBS subtypes, namely IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C), have not been well studied, wrote Sarah Ballou, PhD, of Beth Israel Deaconess Medical Center, Boston, and colleagues.

Source: American Gastroenterological Association

In a study published in Clinical Gastroenterology and Hepatology, the researchers reviewed survey results from 1,587 individuals with IBS-D and 1,667 with IBS-C. The average age of the patients was 47 years, 81% were female, and 90% were white.

Approximately 84% of patients with IBS-C and 93% of those with IBS-D reported abdominal pain, the most common symptom in both groups. Overall, 36% of the 1,885 patients employed or in school reported decreased productivity in those settings.

IBS-C patients were significantly more likely to report that their symptoms caused them to avoid sex, feel self-conscious about their bodies, have trouble concentrating, and feel “not like myself,” compared with IBS-D patients (P less than .004 for all).

IBS-D patients were significantly more likely to report that their symptoms caused them to avoid traveling in general, avoid places without bathrooms, avoid leaving the house, and have trouble making plans, compared with IBS-C patients (P less than .004 for all).

The survey also asked respondents what they would give up for 1 month in exchange for 1 month of relief from IBS symptoms. Overall, approximately 60% said they would give up alcohol, 55% said they would give up caffeine, 40% would give up sex, 24.5% would give up their cell phones, and 21.5% would give up the internet, the researchers wrote.

The study findings were limited by several factors, including the absence of survey respondents with mixed-type IBS, the reliance on self-reports, and the potential for recall bias. Also, the study was not designed to assess the impact of other comorbidities and did not include non-IBS controls, the researchers noted.

However, the results suggest that patients with different IBS subtypes struggle differently in areas of daily function, which has implications for treatment, they wrote.

“This study highlights important differences between IBS-C and IBS-D, which could impact the development and refinement of mind-body therapies for IBS, with tailored treatment goals for each IBS subtype. For example, treatment tailored specifically for IBS-D may be more behaviorally focused (e.g., exposure to specific situations outside the home) while treatment for IBS-C may be more cognitively focused (e.g., evaluating self-esteem and beliefs about self and others) in addition to targeting the bowel dysfunction and pain,” they concluded.

The researchers had no financial conflicts to disclose.

SOURCE: Ballou S et al. Clin Gastroenterol Hepatol. 2019 Aug 13. doi: 10.1016/j.cgh.2019.08.016.

Vitamin C infusion did not improve outcomes related to organ failure, inflammation, or vascular injury for patients with sepsis and acute respiratory distress syndrome, based on data from 167 adults.

Dr_Microbe/Getty Images

“Previous research found that vitamin C attenuates systemic inflammation, corrects sepsis-induced coagulopathy, and attenuates vascular injury,” wrote Alpha A. Fowler III, MD, of Virginia Commonwealth University, Richmond, and colleagues.

To examine the impact of vitamin C infusion on patients with sepsis and acute respiratory distress syndrome (ARDS), the researchers designed the CITRIS-ALI trial, a randomized, double-blind, placebo-controlled study conducted at 7 medical intensive care units in the United States.

In the study, published in JAMA, the researchers randomized 167 adults with sepsis and ARDS to receive high-dose intravenous vitamin C (50 mg/kg in 5% dextrose in water) or placebo (5% dextrose in water only) every 6 hours for 96 hours. The primary outcomes were measures of organ failure based on changes in the modified Sequential Organ Failure Assessment score (mSOFA), inflammation (based on changes in C-reactive protein), and vascular injury based on thrombomodulin.

Overall, no significant differences appeared between the vitamin C and placebo groups, respectively in the three primary outcome measures: change in average SOFA score (3-point change vs. a 3.5-point change) at 96 hours; change in C-reactive protein levels (change of 54.1 mcg/mL vs. 46.1 mcg/mL) at 168 hours; and change in thrombomodulin levels (14.5 ng/mL vs. 13.8 ng/mL) at 168 hours.

The average age of the patients was 55 years, and 54% were men.

The researchers also assessed 46 secondary outcomes. Most of these showed no significant differences between the groups, but 28-day all-cause mortality was significantly lower in the vitamin C group, compared with the placebo group (46.3% vs. 29.8%), the researchers said. Vitamin C also was significantly associated with increased ICU-free days to day 28 and hospital-free days to day 60, compared with placebo.

No significant differences were seen between the groups on 43 other secondary outcomes including ventilator-free days and vasopressor use. However, “these findings were based on analyses that did not account for multiple comparisons and therefore must be considered exploratory,” they said.

“The inability of vitamin C to affect C-reactive protein and thrombomodulin levels in this trial possibly resulted from the advanced stages of sepsis that were present before the development of ARDS,” the researchers noted.

The findings were limited by several factors including the variability in the timing of vitamin C administration and the use of a single high dose of vitamin C, they emphasized. However, the results suggest that further research may be needed to determine the potential of vitamin C for improving outcomes in patients with sepsis and ARDS, they said.

The study was supported by the National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences, VCU Wright Center for Translational Science Award, VCU Investigational Drug Services, and McGuff Pharmaceuticals, who supplied the vitamin C free of charge. Dr. Fowler disclosed funding from Virginia Polytechnic Institute and State University, Richmond; the NHLBI; and study materials from McGuff Pharmaceuticals.

SOURCE: Fowler AA et al. JAMA. 2019 Oct 1;322:1261-70. doi:10.1001/jama.2019.11825.

Vitamin C infusion did not improve outcomes related to organ failure, inflammation, or vascular injury for patients with sepsis and acute respiratory distress syndrome, based on data from 167 adults.

Dr_Microbe/Getty Images

“Previous research found that vitamin C attenuates systemic inflammation, corrects sepsis-induced coagulopathy, and attenuates vascular injury,” wrote Alpha A. Fowler III, MD, of Virginia Commonwealth University, Richmond, and colleagues.

To examine the impact of vitamin C infusion on patients with sepsis and acute respiratory distress syndrome (ARDS), the researchers designed the CITRIS-ALI trial, a randomized, double-blind, placebo-controlled study conducted at 7 medical intensive care units in the United States.

In the study, published in JAMA, the researchers randomized 167 adults with sepsis and ARDS to receive high-dose intravenous vitamin C (50 mg/kg in 5% dextrose in water) or placebo (5% dextrose in water only) every 6 hours for 96 hours. The primary outcomes were measures of organ failure based on changes in the modified Sequential Organ Failure Assessment score (mSOFA), inflammation (based on changes in C-reactive protein), and vascular injury based on thrombomodulin.

Overall, no significant differences appeared between the vitamin C and placebo groups, respectively in the three primary outcome measures: change in average SOFA score (3-point change vs. a 3.5-point change) at 96 hours; change in C-reactive protein levels (change of 54.1 mcg/mL vs. 46.1 mcg/mL) at 168 hours; and change in thrombomodulin levels (14.5 ng/mL vs. 13.8 ng/mL) at 168 hours.

The average age of the patients was 55 years, and 54% were men.

The researchers also assessed 46 secondary outcomes. Most of these showed no significant differences between the groups, but 28-day all-cause mortality was significantly lower in the vitamin C group, compared with the placebo group (46.3% vs. 29.8%), the researchers said. Vitamin C also was significantly associated with increased ICU-free days to day 28 and hospital-free days to day 60, compared with placebo.

No significant differences were seen between the groups on 43 other secondary outcomes including ventilator-free days and vasopressor use. However, “these findings were based on analyses that did not account for multiple comparisons and therefore must be considered exploratory,” they said.

“The inability of vitamin C to affect C-reactive protein and thrombomodulin levels in this trial possibly resulted from the advanced stages of sepsis that were present before the development of ARDS,” the researchers noted.

The findings were limited by several factors including the variability in the timing of vitamin C administration and the use of a single high dose of vitamin C, they emphasized. However, the results suggest that further research may be needed to determine the potential of vitamin C for improving outcomes in patients with sepsis and ARDS, they said.

The study was supported by the National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences, VCU Wright Center for Translational Science Award, VCU Investigational Drug Services, and McGuff Pharmaceuticals, who supplied the vitamin C free of charge. Dr. Fowler disclosed funding from Virginia Polytechnic Institute and State University, Richmond; the NHLBI; and study materials from McGuff Pharmaceuticals.

SOURCE: Fowler AA et al. JAMA. 2019 Oct 1;322:1261-70. doi:10.1001/jama.2019.11825.

Vitamin C infusion did not improve outcomes related to organ failure, inflammation, or vascular injury for patients with sepsis and acute respiratory distress syndrome, based on data from 167 adults.

Dr_Microbe/Getty Images

“Previous research found that vitamin C attenuates systemic inflammation, corrects sepsis-induced coagulopathy, and attenuates vascular injury,” wrote Alpha A. Fowler III, MD, of Virginia Commonwealth University, Richmond, and colleagues.

To examine the impact of vitamin C infusion on patients with sepsis and acute respiratory distress syndrome (ARDS), the researchers designed the CITRIS-ALI trial, a randomized, double-blind, placebo-controlled study conducted at 7 medical intensive care units in the United States.

In the study, published in JAMA, the researchers randomized 167 adults with sepsis and ARDS to receive high-dose intravenous vitamin C (50 mg/kg in 5% dextrose in water) or placebo (5% dextrose in water only) every 6 hours for 96 hours. The primary outcomes were measures of organ failure based on changes in the modified Sequential Organ Failure Assessment score (mSOFA), inflammation (based on changes in C-reactive protein), and vascular injury based on thrombomodulin.

Overall, no significant differences appeared between the vitamin C and placebo groups, respectively in the three primary outcome measures: change in average SOFA score (3-point change vs. a 3.5-point change) at 96 hours; change in C-reactive protein levels (change of 54.1 mcg/mL vs. 46.1 mcg/mL) at 168 hours; and change in thrombomodulin levels (14.5 ng/mL vs. 13.8 ng/mL) at 168 hours.

The average age of the patients was 55 years, and 54% were men.

The researchers also assessed 46 secondary outcomes. Most of these showed no significant differences between the groups, but 28-day all-cause mortality was significantly lower in the vitamin C group, compared with the placebo group (46.3% vs. 29.8%), the researchers said. Vitamin C also was significantly associated with increased ICU-free days to day 28 and hospital-free days to day 60, compared with placebo.

No significant differences were seen between the groups on 43 other secondary outcomes including ventilator-free days and vasopressor use. However, “these findings were based on analyses that did not account for multiple comparisons and therefore must be considered exploratory,” they said.

“The inability of vitamin C to affect C-reactive protein and thrombomodulin levels in this trial possibly resulted from the advanced stages of sepsis that were present before the development of ARDS,” the researchers noted.

The findings were limited by several factors including the variability in the timing of vitamin C administration and the use of a single high dose of vitamin C, they emphasized. However, the results suggest that further research may be needed to determine the potential of vitamin C for improving outcomes in patients with sepsis and ARDS, they said.

The study was supported by the National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences, VCU Wright Center for Translational Science Award, VCU Investigational Drug Services, and McGuff Pharmaceuticals, who supplied the vitamin C free of charge. Dr. Fowler disclosed funding from Virginia Polytechnic Institute and State University, Richmond; the NHLBI; and study materials from McGuff Pharmaceuticals.

SOURCE: Fowler AA et al. JAMA. 2019 Oct 1;322:1261-70. doi:10.1001/jama.2019.11825.