Infectious Diseases

From Lahey Hospital and Medical Center, Burlington, MA (Drs. Liesching and Lei), and Tufts University School of Medicine, Boston, MA (Dr. Liesching)

ABSTRACT

Objective: To compare the utilization of oxygen therapies and clinical outcomes of patients admitted for COVID-19 during the second surge of the pandemic to that of patients admitted during the first surge.

Design: Observational study using a registry database.

Setting: Three hospitals (791 inpatient beds and 76 intensive care unit [ICU] beds) within the Beth Israel Lahey Health system in Massachusetts.

Participants: We included 3183 patients with COVID-19 admitted to hospitals.

Measurements: Baseline data included demographics and comorbidities. Treatments included low-flow supplemental oxygen (2-6 L/min), high-flow oxygen via nasal cannula, and invasive mechanical ventilation. Outcomes included ICU admission, length of stay, ventilator days, and mortality.

Results: A total of 3183 patients were included: 1586 during the first surge and 1597 during the second surge. Compared to the first surge, patients admitted during the second surge had a similar rate of receiving low-flow supplemental oxygen (65.8% vs 64.1%, P = .3), a higher rate of receiving high-flow nasal cannula (15.4% vs 10.8%, P = .0001), and a lower ventilation rate (5.6% vs 9.7%, P < .0001). The outcomes during the second surge were better than those during the first surge: lower ICU admission rate (8.1% vs 12.7%, P < .0001), shorter length of hospital stay (5 vs 6 days, P < .0001), fewer ventilator days (10 vs 16, P = .01), and lower mortality (8.3% vs 19.2%, P < .0001). Among ventilated patients, those who received high-flow nasal cannula had lower mortality.

Conclusion: Compared to the first surge of the COVID-19 pandemic, patients admitted during the second surge had similar likelihood of receiving low-flow supplemental oxygen, were more likely to receive high-flow nasal cannula, were less likely to be ventilated, and had better outcomes.

Keywords: supplemental oxygen, high-flow nasal cannula, ventilator.

The respiratory system receives the major impact of SARS-CoV-2 virus, and hypoxemia has been the predominant diagnosis for patients hospitalized with COVID-19.^1,2 During the initial stage of the pandemic, oxygen therapies and mechanical ventilation were the only choices for these patients.^3-6 Standard-of-care treatment for patients with COVID-19 during the initial surge included oxygen therapies and mechanical ventilation for hypoxemia and medications for comorbidities and COVID-19–associated sequelae, such as multi-organ dysfunction and failure. A report from New York during the first surge (May 2020) showed that among 5700 hospitalized patients with COVID-19, 27.8% received supplemental oxygen and 12.2% received invasive mechanical ventilation.⁷ High-flow nasal cannula (HFNC) oxygen delivery has been utilized widely throughout the pandemic due to its superiority over other noninvasive respiratory support techniques.^8-12 Mechanical ventilation is always necessary for critically ill patients with acute respiratory distress syndrome. However, ventilator scarcity has become a bottleneck in caring for severely ill patients with COVID-19 during the pandemic.¹³

The clinical outcomes of hospitalized COVID-19 patients include a high intubation rate, long length of hospital and intensive care unit (ICU) stay, and high mortality.^14,15 As the pandemic evolved, new medications, including remdesivir, hydroxychloroquine, lopinavir, or interferon β-1a, were used in addition to the standard of care, but these did not result in significantly different mortality from standard of care.¹⁶ Steroids are becoming foundational to the treatment of severe COVID-19 pneumonia, but evidence from high-quality randomized controlled clinical trials is lacking.¹⁷ 

During the first surge from March to May 2020, Massachusetts had the third highest number of COVID-19 cases among states in the United States.¹⁸ In early 2021, COVID-19 cases were climbing close to the peak of the second surge in Massachusetts. In this study, we compared utilization of low-flow supplemental oxygen, HFNC, and mechanical ventilation and clinical outcomes of patients admitted to 3 hospitals in Massachusetts during the second surge of the pandemic to that of patients admitted during the first surge.

Methods

Setting

Beth Israel Lahey Health is a system of academic and teaching hospitals with primary care and specialty care providers. We included 3 centers within the Beth Israel Lahey Health system in Massachusetts: Lahey Hospital and Medical Center, with 335 inpatient hospital beds and 52 critical care beds; Beverly Hospital, with 227 beds and 14 critical care beds; and Winchester Hospital, with 229 beds and 10 ICU beds.

Participants

We included patients admitted to the 3 hospitals with COVID-19 as a primary or secondary diagnosis during the first surge of the pandemic (March 1, 2020 to June 15, 2020) and the second surge (November 15, 2020 to January 27, 2021). The timeframe of the first surge was defined as the window between the start date and the end date of data collection. During the time window of the first surge, 1586 patients were included. The start time of the second surge was defined as the date when the data collection was restarted; the end date was set when the number of patients (1597) accumulated was close to the number of patients in the first surge (1586), so that the two groups had similar sample size.

Study Design

A data registry of COVID-19 patients was created by our institution, and the data were prospectively collected starting in March 2020. We retrospectively extracted data on the following from the registry database for this observational study: demographics and baseline comorbidities; the use of low-flow supplemental oxygen, HFNC, and invasive mechanical ventilator; and ICU admission, length of hospital stay, length of ICU stay, and hospital discharge disposition. Start and end times for each oxygen therapy were not entered in the registry. Data about other oxygen therapies, such as noninvasive positive-pressure ventilation, were not collected in the registry database, and therefore were not included in the analysis.

Statistical Analysis

Continuous variables (eg, age) were tested for data distribution normality using the Shapiro-Wilk test. Normally distributed data were tested using unpaired t-tests and displayed as mean (SD). The skewed data were tested using the Wilcoxon rank sum test and displayed as median (interquartile range [IQR]). The categorical variables were compared using chi-square test. Comparisons with P ≤ .05 were considered significantly different. Statistical analysis for this study was generated using Statistical Analysis Software (SAS), version 9.4 for Windows (SAS Institute Inc.).

Results

Baseline Characteristics

We included 3183 patients: 1586 admitted during the first surge and 1597 admitted during the second surge. Baseline characteristics of patients with COVID-19 admitted during the first and second surges are shown in Table 1. Patients admitted during the second surge were older (73 years vs 71 years, P = .01) and had higher rates of hypertension (64.8% vs 59.6%, P = .003) and asthma (12.9% vs 10.7%, P = .049) but a lower rate of interstitial lung disease (3.3% vs 7.7%, P < .001). Sequential organ failure assessment scores at admission and the rates of other comorbidities were not significantly different between the 2 surges.

 

 

Oxygen Therapies

The number of patients who were hospitalized and received low-flow supplemental oxygen, and/or HFNC, and/or ventilator in the first surge and the second surge is shown in the Figure. Of all patients included, 2067 (64.9%) received low-flow supplemental oxygen; of these, 374 (18.1%) subsequently received HFNC, and 85 (22.7%) of these subsequently received mechanical ventilation. Of all 3183 patients, 417 (13.1%) received HFNC; 43 of these patients received HFNC without receiving low-flow supplemental oxygen, and 98 (23.5%) subsequently received mechanical ventilation. Out of all 3183 patients, 244 (7.7%) received mechanical ventilation; 98 (40.2%) of these received HFNC while the remaining 146 (59.8%) did not. At the beginning of the first surge, the ratio of patients who received invasive mechanical ventilation to patients who received HFNC was close to 1:1 (10/10); the ratio decreased to 6:10 in May and June 2020. At the beginning of the second surge, the ratio was 8:10 and then decreased to 3:10 in December 2020 and January 2021.

As shown in Table 2, the proportion of patients who received low-flow supplemental oxygen during the second surge was similar to that during the first surge (65.8% vs 64.1%, P = .3). Patients admitted during the second surge were more likely to receive HFNC than patients admitted during the first surge (15.4% vs 10.8%, P = .0001). Patients admitted during the second surge were less likely to be ventilated than the patients admitted during the first surge (5.6% vs 9.7%, P < .0001).

Clinical Outcomes

As shown in Table 3, second surge outcomes were much better than first surge outcomes: the ICU admission rate was lower (8.1% vs 12.7%, P < .0001); patients were more likely to be discharged to home (60.2% vs 47.4%, P < .0001), had a shorter length of hospital stay (5 vs 6 days, P < .0001), and had fewer ventilator days (10 vs 16, P = .01); and mortality was lower (8.3% vs 19.2%, P < .0001). There was a trend that length of ICU stay was shorter during the second surge than during the first surge (7 days vs 9 days, P = .09).

As noted (Figure), the ratio of patients who received invasive mechanical ventilation to patients who received HFNC was decreasing during both the first surge and the second surge. To further analyze the relation between ventilator and HFNC, we performed a subgroup analysis for 244 ventilated patients during both surges to compare outcomes between patients who received HFNC and those who did not receive HFNC (Table 4). Ninety-eight (40%) patients received HFNC. Ventilated patients who received HFNC had lower mortality than those patients who did not receive HFNC (31.6% vs 48%, P = .01), but had a longer length of hospital stay (29 days vs 14 days, P < .0001), longer length of ICU stay (17 days vs 9 days, P < .0001), and a higher number of ventilator days (16 vs 11, P = .001).

 

 

Discussion

Our study compared the baseline patient characteristics; utilization of low-flow supplemental oxygen therapy, HFNC, and mechanical ventilation; and clinical outcomes between the first surge (n = 1586) and the second surge (n = 1597) of the COVID-19 pandemic. During both surges, about two-thirds of admitted patients received low-flow supplemental oxygen. A higher proportion of the admitted patients received HFNC during the second surge than during the first surge, while the intubation rate was lower during the second surge than during the first surge.

Reported low-flow supplemental oxygen use ranged from 28% to 63% depending on the cohort characteristics and location during the first surge.^6,7,19 A report from New York during the first surge (March 1 to April 4, 2020) showed that among 5700 hospitalized patients with COVID-19, 27.8% received low-flow supplemental oxygen.⁷ HFNC is recommended in guidelines on management of patients with acute respiratory failure due to COVID-19.²⁰ In our study, HFNC was utilized in a higher proportion of patients admitted for COVID-19 during the second surge (15.5% vs 10.8%, P = .0001). During the early pandemic period in Wuhan, China, 11% to 21% of admitted COVID-19 patients received HFNC.^21,22 Utilization of HFNC in New York during the first surge (March to May 2020) varied from 5% to 14.3% of patients admitted with COVID-19.^23,24 Our subgroup analysis of the ventilated patients showed that patients who received HFNC had lower mortality than those who did not (31.6% vs 48.0%, P = .011). Comparably, a report from Paris, France, showed that among patients admitted to ICUs for acute hypoxemic respiratory failure, those who received HFNC had lower mortality at day 60 than those who did not (21% vs 31%, P = .052).²⁵ Our recent analysis showed that patients treated with HFNC prior to mechanical ventilation had lower mortality than those treated with only conventional oxygen (30% vs 52%, P = .05).²⁶ In this subgroup analysis, we could not determine if HFNC treatment was administered before or after ventilation because HFNC was entered as dichotomous data (“Yes” or “No”) in the registry database. We merely showed the beneficial effect of HFNC on reducing mortality for ventilated COVID-19 patients, but did not mean to focus on how and when to apply HFNC.

We observed that the patients admitted during the second surge were less likely to be ventilated than the patients admitted during the first surge (5.6% vs 9.7%, P < .0001). During the first surge in New York, among 5700 patients admitted with COVID-19, 12.2% received invasive mechanical ventilation.⁷ In another report, also from New York during the first surge, 26.1% of 2015 hospitalized COVID-19 patients received mechanical ventilation.²⁷ In our study, the ventilation rate of 9.7% during the first surge was lower.

Outcomes during the second surge were better than during the first surge, including ICU admission rate, hospital and ICU length of stay, ventilator days, and mortality. The mortality was 19.2% during the first surge vs 8.3% during the second surge (P < .0001). The mortality of 19.2% was lower than the 30.6% mortality reported for 2015 hospitalized COVID-19 patients in New York during the first surge.²⁷ A retrospective study showed that early administration of remdesivir was associated with reduced ICU admission, ventilation use, and mortality.²⁸ The RECOVERY clinical trial showed that dexamethasone improved mortality for COVID-19 patients who received respiratory support, but not for patients who did not receive any respiratory support.²⁹ Perhaps some, if not all, of the improvement in ICU admission and mortality during the second surge was attributed to the new medications, such as antivirals and steroids.

The length of hospital stay for patients with moderate to severe COVID-19 varied from 4 to 53 days at different locations of the world, as shown in a meta-analysis by Rees and colleagues.³⁰ Our results showing a length of stay of 6 days during the first surge and 5 days during the second surge fell into the shorter end of this range. In a retrospective analysis of 1643 adults with severe COVID-19 admitted to hospitals in New York City between March 9, 2020 and April 23, 2020, median hospital length of stay was 7 (IQR, 3-14) days.³¹ For the ventilated patients in our study, the length of stay of 14 days (did not receive HFNC) and 29 days (received HFNC) was much longer. This longer length of stay might be attributed to the patients in our study being older and having more severe comorbidities.

The main purpose of this study was to compare the oxygen therapies and outcomes between 2 surges. It is difficult to associate the clinical outcomes with the oxygen therapies because new therapies and medications were available after the first surge. It was not possible to adjust the outcomes with confounders (other therapies and medications) because the registry data did not include the new therapies and medications.

A strength of this study was that we included a large, balanced number of patients in the first surge and the second surge. We did not plan the sample size in both groups as we could not predict the number of admissions. We set the end date of data collection for analysis as the time when the number of patients admitted during the second surge was similar to the number of patients admitted during the first surge. A limitation was that the registry database was created by the institution and was not designed solely for this study. The data for oxygen therapies were limited to low-flow supplemental oxygen, HFNC, and invasive mechanical ventilation; data for noninvasive ventilation were not included.

Conclusion

At our centers, during the second surge of COVID-19 pandemic, patients hospitalized with COVID-19 infection were more likely to receive HFNC but less likely to be ventilated. Compared to the first surge, the hospitalized patients with COVID-19 infection had a lower ICU admission rate, shorter length of hospital stay, fewer ventilator days, and lower mortality. For ventilated patients, those who received HFNC had lower mortality than those who did not.

Corresponding author: Timothy N. Liesching, MD, 41 Mall Road, Burlington, MA 01805; Timothy.N.Liesching@lahey.org

Disclosures: None reported.

doi:10.12788/jcom.0086

From Lahey Hospital and Medical Center, Burlington, MA (Drs. Liesching and Lei), and Tufts University School of Medicine, Boston, MA (Dr. Liesching)

ABSTRACT

Objective: To compare the utilization of oxygen therapies and clinical outcomes of patients admitted for COVID-19 during the second surge of the pandemic to that of patients admitted during the first surge.

Design: Observational study using a registry database.

Setting: Three hospitals (791 inpatient beds and 76 intensive care unit [ICU] beds) within the Beth Israel Lahey Health system in Massachusetts.

Participants: We included 3183 patients with COVID-19 admitted to hospitals.

Measurements: Baseline data included demographics and comorbidities. Treatments included low-flow supplemental oxygen (2-6 L/min), high-flow oxygen via nasal cannula, and invasive mechanical ventilation. Outcomes included ICU admission, length of stay, ventilator days, and mortality.

Results: A total of 3183 patients were included: 1586 during the first surge and 1597 during the second surge. Compared to the first surge, patients admitted during the second surge had a similar rate of receiving low-flow supplemental oxygen (65.8% vs 64.1%, P = .3), a higher rate of receiving high-flow nasal cannula (15.4% vs 10.8%, P = .0001), and a lower ventilation rate (5.6% vs 9.7%, P < .0001). The outcomes during the second surge were better than those during the first surge: lower ICU admission rate (8.1% vs 12.7%, P < .0001), shorter length of hospital stay (5 vs 6 days, P < .0001), fewer ventilator days (10 vs 16, P = .01), and lower mortality (8.3% vs 19.2%, P < .0001). Among ventilated patients, those who received high-flow nasal cannula had lower mortality.

Conclusion: Compared to the first surge of the COVID-19 pandemic, patients admitted during the second surge had similar likelihood of receiving low-flow supplemental oxygen, were more likely to receive high-flow nasal cannula, were less likely to be ventilated, and had better outcomes.

Keywords: supplemental oxygen, high-flow nasal cannula, ventilator.

The respiratory system receives the major impact of SARS-CoV-2 virus, and hypoxemia has been the predominant diagnosis for patients hospitalized with COVID-19.^1,2 During the initial stage of the pandemic, oxygen therapies and mechanical ventilation were the only choices for these patients.^3-6 Standard-of-care treatment for patients with COVID-19 during the initial surge included oxygen therapies and mechanical ventilation for hypoxemia and medications for comorbidities and COVID-19–associated sequelae, such as multi-organ dysfunction and failure. A report from New York during the first surge (May 2020) showed that among 5700 hospitalized patients with COVID-19, 27.8% received supplemental oxygen and 12.2% received invasive mechanical ventilation.⁷ High-flow nasal cannula (HFNC) oxygen delivery has been utilized widely throughout the pandemic due to its superiority over other noninvasive respiratory support techniques.^8-12 Mechanical ventilation is always necessary for critically ill patients with acute respiratory distress syndrome. However, ventilator scarcity has become a bottleneck in caring for severely ill patients with COVID-19 during the pandemic.¹³

The clinical outcomes of hospitalized COVID-19 patients include a high intubation rate, long length of hospital and intensive care unit (ICU) stay, and high mortality.^14,15 As the pandemic evolved, new medications, including remdesivir, hydroxychloroquine, lopinavir, or interferon β-1a, were used in addition to the standard of care, but these did not result in significantly different mortality from standard of care.¹⁶ Steroids are becoming foundational to the treatment of severe COVID-19 pneumonia, but evidence from high-quality randomized controlled clinical trials is lacking.¹⁷ 

During the first surge from March to May 2020, Massachusetts had the third highest number of COVID-19 cases among states in the United States.¹⁸ In early 2021, COVID-19 cases were climbing close to the peak of the second surge in Massachusetts. In this study, we compared utilization of low-flow supplemental oxygen, HFNC, and mechanical ventilation and clinical outcomes of patients admitted to 3 hospitals in Massachusetts during the second surge of the pandemic to that of patients admitted during the first surge.

Methods

Setting

Beth Israel Lahey Health is a system of academic and teaching hospitals with primary care and specialty care providers. We included 3 centers within the Beth Israel Lahey Health system in Massachusetts: Lahey Hospital and Medical Center, with 335 inpatient hospital beds and 52 critical care beds; Beverly Hospital, with 227 beds and 14 critical care beds; and Winchester Hospital, with 229 beds and 10 ICU beds.

Participants

We included patients admitted to the 3 hospitals with COVID-19 as a primary or secondary diagnosis during the first surge of the pandemic (March 1, 2020 to June 15, 2020) and the second surge (November 15, 2020 to January 27, 2021). The timeframe of the first surge was defined as the window between the start date and the end date of data collection. During the time window of the first surge, 1586 patients were included. The start time of the second surge was defined as the date when the data collection was restarted; the end date was set when the number of patients (1597) accumulated was close to the number of patients in the first surge (1586), so that the two groups had similar sample size.

Study Design

A data registry of COVID-19 patients was created by our institution, and the data were prospectively collected starting in March 2020. We retrospectively extracted data on the following from the registry database for this observational study: demographics and baseline comorbidities; the use of low-flow supplemental oxygen, HFNC, and invasive mechanical ventilator; and ICU admission, length of hospital stay, length of ICU stay, and hospital discharge disposition. Start and end times for each oxygen therapy were not entered in the registry. Data about other oxygen therapies, such as noninvasive positive-pressure ventilation, were not collected in the registry database, and therefore were not included in the analysis.

Statistical Analysis

Continuous variables (eg, age) were tested for data distribution normality using the Shapiro-Wilk test. Normally distributed data were tested using unpaired t-tests and displayed as mean (SD). The skewed data were tested using the Wilcoxon rank sum test and displayed as median (interquartile range [IQR]). The categorical variables were compared using chi-square test. Comparisons with P ≤ .05 were considered significantly different. Statistical analysis for this study was generated using Statistical Analysis Software (SAS), version 9.4 for Windows (SAS Institute Inc.).

Results

Baseline Characteristics

We included 3183 patients: 1586 admitted during the first surge and 1597 admitted during the second surge. Baseline characteristics of patients with COVID-19 admitted during the first and second surges are shown in Table 1. Patients admitted during the second surge were older (73 years vs 71 years, P = .01) and had higher rates of hypertension (64.8% vs 59.6%, P = .003) and asthma (12.9% vs 10.7%, P = .049) but a lower rate of interstitial lung disease (3.3% vs 7.7%, P < .001). Sequential organ failure assessment scores at admission and the rates of other comorbidities were not significantly different between the 2 surges.

 

 

Oxygen Therapies

The number of patients who were hospitalized and received low-flow supplemental oxygen, and/or HFNC, and/or ventilator in the first surge and the second surge is shown in the Figure. Of all patients included, 2067 (64.9%) received low-flow supplemental oxygen; of these, 374 (18.1%) subsequently received HFNC, and 85 (22.7%) of these subsequently received mechanical ventilation. Of all 3183 patients, 417 (13.1%) received HFNC; 43 of these patients received HFNC without receiving low-flow supplemental oxygen, and 98 (23.5%) subsequently received mechanical ventilation. Out of all 3183 patients, 244 (7.7%) received mechanical ventilation; 98 (40.2%) of these received HFNC while the remaining 146 (59.8%) did not. At the beginning of the first surge, the ratio of patients who received invasive mechanical ventilation to patients who received HFNC was close to 1:1 (10/10); the ratio decreased to 6:10 in May and June 2020. At the beginning of the second surge, the ratio was 8:10 and then decreased to 3:10 in December 2020 and January 2021.

As shown in Table 2, the proportion of patients who received low-flow supplemental oxygen during the second surge was similar to that during the first surge (65.8% vs 64.1%, P = .3). Patients admitted during the second surge were more likely to receive HFNC than patients admitted during the first surge (15.4% vs 10.8%, P = .0001). Patients admitted during the second surge were less likely to be ventilated than the patients admitted during the first surge (5.6% vs 9.7%, P < .0001).

Clinical Outcomes

As shown in Table 3, second surge outcomes were much better than first surge outcomes: the ICU admission rate was lower (8.1% vs 12.7%, P < .0001); patients were more likely to be discharged to home (60.2% vs 47.4%, P < .0001), had a shorter length of hospital stay (5 vs 6 days, P < .0001), and had fewer ventilator days (10 vs 16, P = .01); and mortality was lower (8.3% vs 19.2%, P < .0001). There was a trend that length of ICU stay was shorter during the second surge than during the first surge (7 days vs 9 days, P = .09).

As noted (Figure), the ratio of patients who received invasive mechanical ventilation to patients who received HFNC was decreasing during both the first surge and the second surge. To further analyze the relation between ventilator and HFNC, we performed a subgroup analysis for 244 ventilated patients during both surges to compare outcomes between patients who received HFNC and those who did not receive HFNC (Table 4). Ninety-eight (40%) patients received HFNC. Ventilated patients who received HFNC had lower mortality than those patients who did not receive HFNC (31.6% vs 48%, P = .01), but had a longer length of hospital stay (29 days vs 14 days, P < .0001), longer length of ICU stay (17 days vs 9 days, P < .0001), and a higher number of ventilator days (16 vs 11, P = .001).

 

 

Discussion

Our study compared the baseline patient characteristics; utilization of low-flow supplemental oxygen therapy, HFNC, and mechanical ventilation; and clinical outcomes between the first surge (n = 1586) and the second surge (n = 1597) of the COVID-19 pandemic. During both surges, about two-thirds of admitted patients received low-flow supplemental oxygen. A higher proportion of the admitted patients received HFNC during the second surge than during the first surge, while the intubation rate was lower during the second surge than during the first surge.

Reported low-flow supplemental oxygen use ranged from 28% to 63% depending on the cohort characteristics and location during the first surge.^6,7,19 A report from New York during the first surge (March 1 to April 4, 2020) showed that among 5700 hospitalized patients with COVID-19, 27.8% received low-flow supplemental oxygen.⁷ HFNC is recommended in guidelines on management of patients with acute respiratory failure due to COVID-19.²⁰ In our study, HFNC was utilized in a higher proportion of patients admitted for COVID-19 during the second surge (15.5% vs 10.8%, P = .0001). During the early pandemic period in Wuhan, China, 11% to 21% of admitted COVID-19 patients received HFNC.^21,22 Utilization of HFNC in New York during the first surge (March to May 2020) varied from 5% to 14.3% of patients admitted with COVID-19.^23,24 Our subgroup analysis of the ventilated patients showed that patients who received HFNC had lower mortality than those who did not (31.6% vs 48.0%, P = .011). Comparably, a report from Paris, France, showed that among patients admitted to ICUs for acute hypoxemic respiratory failure, those who received HFNC had lower mortality at day 60 than those who did not (21% vs 31%, P = .052).²⁵ Our recent analysis showed that patients treated with HFNC prior to mechanical ventilation had lower mortality than those treated with only conventional oxygen (30% vs 52%, P = .05).²⁶ In this subgroup analysis, we could not determine if HFNC treatment was administered before or after ventilation because HFNC was entered as dichotomous data (“Yes” or “No”) in the registry database. We merely showed the beneficial effect of HFNC on reducing mortality for ventilated COVID-19 patients, but did not mean to focus on how and when to apply HFNC.

We observed that the patients admitted during the second surge were less likely to be ventilated than the patients admitted during the first surge (5.6% vs 9.7%, P < .0001). During the first surge in New York, among 5700 patients admitted with COVID-19, 12.2% received invasive mechanical ventilation.⁷ In another report, also from New York during the first surge, 26.1% of 2015 hospitalized COVID-19 patients received mechanical ventilation.²⁷ In our study, the ventilation rate of 9.7% during the first surge was lower.

Outcomes during the second surge were better than during the first surge, including ICU admission rate, hospital and ICU length of stay, ventilator days, and mortality. The mortality was 19.2% during the first surge vs 8.3% during the second surge (P < .0001). The mortality of 19.2% was lower than the 30.6% mortality reported for 2015 hospitalized COVID-19 patients in New York during the first surge.²⁷ A retrospective study showed that early administration of remdesivir was associated with reduced ICU admission, ventilation use, and mortality.²⁸ The RECOVERY clinical trial showed that dexamethasone improved mortality for COVID-19 patients who received respiratory support, but not for patients who did not receive any respiratory support.²⁹ Perhaps some, if not all, of the improvement in ICU admission and mortality during the second surge was attributed to the new medications, such as antivirals and steroids.

The length of hospital stay for patients with moderate to severe COVID-19 varied from 4 to 53 days at different locations of the world, as shown in a meta-analysis by Rees and colleagues.³⁰ Our results showing a length of stay of 6 days during the first surge and 5 days during the second surge fell into the shorter end of this range. In a retrospective analysis of 1643 adults with severe COVID-19 admitted to hospitals in New York City between March 9, 2020 and April 23, 2020, median hospital length of stay was 7 (IQR, 3-14) days.³¹ For the ventilated patients in our study, the length of stay of 14 days (did not receive HFNC) and 29 days (received HFNC) was much longer. This longer length of stay might be attributed to the patients in our study being older and having more severe comorbidities.

The main purpose of this study was to compare the oxygen therapies and outcomes between 2 surges. It is difficult to associate the clinical outcomes with the oxygen therapies because new therapies and medications were available after the first surge. It was not possible to adjust the outcomes with confounders (other therapies and medications) because the registry data did not include the new therapies and medications.

A strength of this study was that we included a large, balanced number of patients in the first surge and the second surge. We did not plan the sample size in both groups as we could not predict the number of admissions. We set the end date of data collection for analysis as the time when the number of patients admitted during the second surge was similar to the number of patients admitted during the first surge. A limitation was that the registry database was created by the institution and was not designed solely for this study. The data for oxygen therapies were limited to low-flow supplemental oxygen, HFNC, and invasive mechanical ventilation; data for noninvasive ventilation were not included.

Conclusion

At our centers, during the second surge of COVID-19 pandemic, patients hospitalized with COVID-19 infection were more likely to receive HFNC but less likely to be ventilated. Compared to the first surge, the hospitalized patients with COVID-19 infection had a lower ICU admission rate, shorter length of hospital stay, fewer ventilator days, and lower mortality. For ventilated patients, those who received HFNC had lower mortality than those who did not.

Corresponding author: Timothy N. Liesching, MD, 41 Mall Road, Burlington, MA 01805; Timothy.N.Liesching@lahey.org

Disclosures: None reported.

doi:10.12788/jcom.0086

From Lahey Hospital and Medical Center, Burlington, MA (Drs. Liesching and Lei), and Tufts University School of Medicine, Boston, MA (Dr. Liesching)

ABSTRACT

Objective: To compare the utilization of oxygen therapies and clinical outcomes of patients admitted for COVID-19 during the second surge of the pandemic to that of patients admitted during the first surge.

Design: Observational study using a registry database.

Setting: Three hospitals (791 inpatient beds and 76 intensive care unit [ICU] beds) within the Beth Israel Lahey Health system in Massachusetts.

Participants: We included 3183 patients with COVID-19 admitted to hospitals.

Measurements: Baseline data included demographics and comorbidities. Treatments included low-flow supplemental oxygen (2-6 L/min), high-flow oxygen via nasal cannula, and invasive mechanical ventilation. Outcomes included ICU admission, length of stay, ventilator days, and mortality.

Results: A total of 3183 patients were included: 1586 during the first surge and 1597 during the second surge. Compared to the first surge, patients admitted during the second surge had a similar rate of receiving low-flow supplemental oxygen (65.8% vs 64.1%, P = .3), a higher rate of receiving high-flow nasal cannula (15.4% vs 10.8%, P = .0001), and a lower ventilation rate (5.6% vs 9.7%, P < .0001). The outcomes during the second surge were better than those during the first surge: lower ICU admission rate (8.1% vs 12.7%, P < .0001), shorter length of hospital stay (5 vs 6 days, P < .0001), fewer ventilator days (10 vs 16, P = .01), and lower mortality (8.3% vs 19.2%, P < .0001). Among ventilated patients, those who received high-flow nasal cannula had lower mortality.

Conclusion: Compared to the first surge of the COVID-19 pandemic, patients admitted during the second surge had similar likelihood of receiving low-flow supplemental oxygen, were more likely to receive high-flow nasal cannula, were less likely to be ventilated, and had better outcomes.

Keywords: supplemental oxygen, high-flow nasal cannula, ventilator.

The respiratory system receives the major impact of SARS-CoV-2 virus, and hypoxemia has been the predominant diagnosis for patients hospitalized with COVID-19.^1,2 During the initial stage of the pandemic, oxygen therapies and mechanical ventilation were the only choices for these patients.^3-6 Standard-of-care treatment for patients with COVID-19 during the initial surge included oxygen therapies and mechanical ventilation for hypoxemia and medications for comorbidities and COVID-19–associated sequelae, such as multi-organ dysfunction and failure. A report from New York during the first surge (May 2020) showed that among 5700 hospitalized patients with COVID-19, 27.8% received supplemental oxygen and 12.2% received invasive mechanical ventilation.⁷ High-flow nasal cannula (HFNC) oxygen delivery has been utilized widely throughout the pandemic due to its superiority over other noninvasive respiratory support techniques.^8-12 Mechanical ventilation is always necessary for critically ill patients with acute respiratory distress syndrome. However, ventilator scarcity has become a bottleneck in caring for severely ill patients with COVID-19 during the pandemic.¹³

The clinical outcomes of hospitalized COVID-19 patients include a high intubation rate, long length of hospital and intensive care unit (ICU) stay, and high mortality.^14,15 As the pandemic evolved, new medications, including remdesivir, hydroxychloroquine, lopinavir, or interferon β-1a, were used in addition to the standard of care, but these did not result in significantly different mortality from standard of care.¹⁶ Steroids are becoming foundational to the treatment of severe COVID-19 pneumonia, but evidence from high-quality randomized controlled clinical trials is lacking.¹⁷ 

During the first surge from March to May 2020, Massachusetts had the third highest number of COVID-19 cases among states in the United States.¹⁸ In early 2021, COVID-19 cases were climbing close to the peak of the second surge in Massachusetts. In this study, we compared utilization of low-flow supplemental oxygen, HFNC, and mechanical ventilation and clinical outcomes of patients admitted to 3 hospitals in Massachusetts during the second surge of the pandemic to that of patients admitted during the first surge.

Methods

Setting

Beth Israel Lahey Health is a system of academic and teaching hospitals with primary care and specialty care providers. We included 3 centers within the Beth Israel Lahey Health system in Massachusetts: Lahey Hospital and Medical Center, with 335 inpatient hospital beds and 52 critical care beds; Beverly Hospital, with 227 beds and 14 critical care beds; and Winchester Hospital, with 229 beds and 10 ICU beds.

Participants

We included patients admitted to the 3 hospitals with COVID-19 as a primary or secondary diagnosis during the first surge of the pandemic (March 1, 2020 to June 15, 2020) and the second surge (November 15, 2020 to January 27, 2021). The timeframe of the first surge was defined as the window between the start date and the end date of data collection. During the time window of the first surge, 1586 patients were included. The start time of the second surge was defined as the date when the data collection was restarted; the end date was set when the number of patients (1597) accumulated was close to the number of patients in the first surge (1586), so that the two groups had similar sample size.

Study Design

A data registry of COVID-19 patients was created by our institution, and the data were prospectively collected starting in March 2020. We retrospectively extracted data on the following from the registry database for this observational study: demographics and baseline comorbidities; the use of low-flow supplemental oxygen, HFNC, and invasive mechanical ventilator; and ICU admission, length of hospital stay, length of ICU stay, and hospital discharge disposition. Start and end times for each oxygen therapy were not entered in the registry. Data about other oxygen therapies, such as noninvasive positive-pressure ventilation, were not collected in the registry database, and therefore were not included in the analysis.

Statistical Analysis

Continuous variables (eg, age) were tested for data distribution normality using the Shapiro-Wilk test. Normally distributed data were tested using unpaired t-tests and displayed as mean (SD). The skewed data were tested using the Wilcoxon rank sum test and displayed as median (interquartile range [IQR]). The categorical variables were compared using chi-square test. Comparisons with P ≤ .05 were considered significantly different. Statistical analysis for this study was generated using Statistical Analysis Software (SAS), version 9.4 for Windows (SAS Institute Inc.).

Results

Baseline Characteristics

We included 3183 patients: 1586 admitted during the first surge and 1597 admitted during the second surge. Baseline characteristics of patients with COVID-19 admitted during the first and second surges are shown in Table 1. Patients admitted during the second surge were older (73 years vs 71 years, P = .01) and had higher rates of hypertension (64.8% vs 59.6%, P = .003) and asthma (12.9% vs 10.7%, P = .049) but a lower rate of interstitial lung disease (3.3% vs 7.7%, P < .001). Sequential organ failure assessment scores at admission and the rates of other comorbidities were not significantly different between the 2 surges.

 

 

Oxygen Therapies

The number of patients who were hospitalized and received low-flow supplemental oxygen, and/or HFNC, and/or ventilator in the first surge and the second surge is shown in the Figure. Of all patients included, 2067 (64.9%) received low-flow supplemental oxygen; of these, 374 (18.1%) subsequently received HFNC, and 85 (22.7%) of these subsequently received mechanical ventilation. Of all 3183 patients, 417 (13.1%) received HFNC; 43 of these patients received HFNC without receiving low-flow supplemental oxygen, and 98 (23.5%) subsequently received mechanical ventilation. Out of all 3183 patients, 244 (7.7%) received mechanical ventilation; 98 (40.2%) of these received HFNC while the remaining 146 (59.8%) did not. At the beginning of the first surge, the ratio of patients who received invasive mechanical ventilation to patients who received HFNC was close to 1:1 (10/10); the ratio decreased to 6:10 in May and June 2020. At the beginning of the second surge, the ratio was 8:10 and then decreased to 3:10 in December 2020 and January 2021.

As shown in Table 2, the proportion of patients who received low-flow supplemental oxygen during the second surge was similar to that during the first surge (65.8% vs 64.1%, P = .3). Patients admitted during the second surge were more likely to receive HFNC than patients admitted during the first surge (15.4% vs 10.8%, P = .0001). Patients admitted during the second surge were less likely to be ventilated than the patients admitted during the first surge (5.6% vs 9.7%, P < .0001).

Clinical Outcomes

As shown in Table 3, second surge outcomes were much better than first surge outcomes: the ICU admission rate was lower (8.1% vs 12.7%, P < .0001); patients were more likely to be discharged to home (60.2% vs 47.4%, P < .0001), had a shorter length of hospital stay (5 vs 6 days, P < .0001), and had fewer ventilator days (10 vs 16, P = .01); and mortality was lower (8.3% vs 19.2%, P < .0001). There was a trend that length of ICU stay was shorter during the second surge than during the first surge (7 days vs 9 days, P = .09).

As noted (Figure), the ratio of patients who received invasive mechanical ventilation to patients who received HFNC was decreasing during both the first surge and the second surge. To further analyze the relation between ventilator and HFNC, we performed a subgroup analysis for 244 ventilated patients during both surges to compare outcomes between patients who received HFNC and those who did not receive HFNC (Table 4). Ninety-eight (40%) patients received HFNC. Ventilated patients who received HFNC had lower mortality than those patients who did not receive HFNC (31.6% vs 48%, P = .01), but had a longer length of hospital stay (29 days vs 14 days, P < .0001), longer length of ICU stay (17 days vs 9 days, P < .0001), and a higher number of ventilator days (16 vs 11, P = .001).

 

 

Discussion

Our study compared the baseline patient characteristics; utilization of low-flow supplemental oxygen therapy, HFNC, and mechanical ventilation; and clinical outcomes between the first surge (n = 1586) and the second surge (n = 1597) of the COVID-19 pandemic. During both surges, about two-thirds of admitted patients received low-flow supplemental oxygen. A higher proportion of the admitted patients received HFNC during the second surge than during the first surge, while the intubation rate was lower during the second surge than during the first surge.

Reported low-flow supplemental oxygen use ranged from 28% to 63% depending on the cohort characteristics and location during the first surge.^6,7,19 A report from New York during the first surge (March 1 to April 4, 2020) showed that among 5700 hospitalized patients with COVID-19, 27.8% received low-flow supplemental oxygen.⁷ HFNC is recommended in guidelines on management of patients with acute respiratory failure due to COVID-19.²⁰ In our study, HFNC was utilized in a higher proportion of patients admitted for COVID-19 during the second surge (15.5% vs 10.8%, P = .0001). During the early pandemic period in Wuhan, China, 11% to 21% of admitted COVID-19 patients received HFNC.^21,22 Utilization of HFNC in New York during the first surge (March to May 2020) varied from 5% to 14.3% of patients admitted with COVID-19.^23,24 Our subgroup analysis of the ventilated patients showed that patients who received HFNC had lower mortality than those who did not (31.6% vs 48.0%, P = .011). Comparably, a report from Paris, France, showed that among patients admitted to ICUs for acute hypoxemic respiratory failure, those who received HFNC had lower mortality at day 60 than those who did not (21% vs 31%, P = .052).²⁵ Our recent analysis showed that patients treated with HFNC prior to mechanical ventilation had lower mortality than those treated with only conventional oxygen (30% vs 52%, P = .05).²⁶ In this subgroup analysis, we could not determine if HFNC treatment was administered before or after ventilation because HFNC was entered as dichotomous data (“Yes” or “No”) in the registry database. We merely showed the beneficial effect of HFNC on reducing mortality for ventilated COVID-19 patients, but did not mean to focus on how and when to apply HFNC.

We observed that the patients admitted during the second surge were less likely to be ventilated than the patients admitted during the first surge (5.6% vs 9.7%, P < .0001). During the first surge in New York, among 5700 patients admitted with COVID-19, 12.2% received invasive mechanical ventilation.⁷ In another report, also from New York during the first surge, 26.1% of 2015 hospitalized COVID-19 patients received mechanical ventilation.²⁷ In our study, the ventilation rate of 9.7% during the first surge was lower.

Outcomes during the second surge were better than during the first surge, including ICU admission rate, hospital and ICU length of stay, ventilator days, and mortality. The mortality was 19.2% during the first surge vs 8.3% during the second surge (P < .0001). The mortality of 19.2% was lower than the 30.6% mortality reported for 2015 hospitalized COVID-19 patients in New York during the first surge.²⁷ A retrospective study showed that early administration of remdesivir was associated with reduced ICU admission, ventilation use, and mortality.²⁸ The RECOVERY clinical trial showed that dexamethasone improved mortality for COVID-19 patients who received respiratory support, but not for patients who did not receive any respiratory support.²⁹ Perhaps some, if not all, of the improvement in ICU admission and mortality during the second surge was attributed to the new medications, such as antivirals and steroids.

The length of hospital stay for patients with moderate to severe COVID-19 varied from 4 to 53 days at different locations of the world, as shown in a meta-analysis by Rees and colleagues.³⁰ Our results showing a length of stay of 6 days during the first surge and 5 days during the second surge fell into the shorter end of this range. In a retrospective analysis of 1643 adults with severe COVID-19 admitted to hospitals in New York City between March 9, 2020 and April 23, 2020, median hospital length of stay was 7 (IQR, 3-14) days.³¹ For the ventilated patients in our study, the length of stay of 14 days (did not receive HFNC) and 29 days (received HFNC) was much longer. This longer length of stay might be attributed to the patients in our study being older and having more severe comorbidities.

The main purpose of this study was to compare the oxygen therapies and outcomes between 2 surges. It is difficult to associate the clinical outcomes with the oxygen therapies because new therapies and medications were available after the first surge. It was not possible to adjust the outcomes with confounders (other therapies and medications) because the registry data did not include the new therapies and medications.

A strength of this study was that we included a large, balanced number of patients in the first surge and the second surge. We did not plan the sample size in both groups as we could not predict the number of admissions. We set the end date of data collection for analysis as the time when the number of patients admitted during the second surge was similar to the number of patients admitted during the first surge. A limitation was that the registry database was created by the institution and was not designed solely for this study. The data for oxygen therapies were limited to low-flow supplemental oxygen, HFNC, and invasive mechanical ventilation; data for noninvasive ventilation were not included.

Conclusion

At our centers, during the second surge of COVID-19 pandemic, patients hospitalized with COVID-19 infection were more likely to receive HFNC but less likely to be ventilated. Compared to the first surge, the hospitalized patients with COVID-19 infection had a lower ICU admission rate, shorter length of hospital stay, fewer ventilator days, and lower mortality. For ventilated patients, those who received HFNC had lower mortality than those who did not.

Corresponding author: Timothy N. Liesching, MD, 41 Mall Road, Burlington, MA 01805; Timothy.N.Liesching@lahey.org

Disclosures: None reported.

doi:10.12788/jcom.0086

Get the science right. I have spent years researching and reflecting on what makes the best physicians, the best medicine, the optimal organized medical system, and the best medical ethics and law to support all of it. I have traveled to almost innumerable conferences to discuss these topics with colleagues who have similar goals. Time and time again, I come back to the conclusion that, in the modern era, the second-most important thing to do is to get the science right.

The practice of medicine in my Western world can be traced back to Hippocrates and earlier. The practice of nursing has other milestones. The healing arts have different points of origin in other cultures, such as China. In a modern world of mass communication, these various historical paths are converging on scientific evidence. The science to support medicine has always had flaws, but it has fared better than the other options. Sometimes, the science was so sketchy that the key was to believe in whatever the shaman was providing. But for the past 100 years, science, rather than tradition and hierarchy, has been relied upon to guide policy and action. For the past 50 years, evidence-based medicine has ascended. Have we become better than the snake oil salesmen of the late 19th century?

Modern health care is far from perfect. The pandemic has been a major stressor to the health care system. The pandemic has revealed flaws and weaknesses, including inequity in access to care, health illiteracy, and a shaky moral compass balancing individual liberty and social good. Overall, despite multiple mistakes dealing with a novel threat, I think the institutions promoting science have performed well during the pandemic, especially when compared with the moral and governmental institutions encouraging ethical behavior and making policies to promote justice.

My highest praise would be for the professionalism of health care workers. Nurses and physicians have staffed the hospitals and clinics caring for people when the hallways were overflowing for days without end. Without the commitment, the teamwork, and the courage to provide that care, the death toll would have been much higher and the suffering unimaginable. My observation is that these people were not motivated by an abstract primum non nocere, first do no harm. It was the commitment to love one’s neighbor and care for the sick. This dedication is the first most important thing in professionalism.

Part of what fuels that commitment is a belief that what they are doing makes a difference. The belief is stronger when there is measurable, scientific evidence that a difference is being made. The scientific decisions have not been perfect, but at this point the evidence is clear that the shutdown flattened the curve. Vaccines saved lives and will continue to do so. Masks saved lives. Nursing care, particularly intensive care, reduced the case fatality rate and assuaged suffering and grief.

What lessons about training new providers can be gleaned from the past 2 years? Those who teach professionalism for physicians, nurses, and other health care workers should strengthen the common value systems that undergird the commitment people have to the patients and the professions. In the face of postmodern nihilism and relativism, virtues need to be clarified and reinforced. In the face of political polarization which seeks to make a political affiliation the locus of loyalty and commitment, emphasize the fellowship of the health care professions.

To me as a scientist, a key lesson is that we need to be better at getting the science right. Two years ago I was wiping some groceries with alcohol and quarantining cans in shopping bags in the corner of the kitchen for 24 hours before shelving them. I still push elevator buttons with my knuckles. The Centers for Disease Control and Prevention needs to revamp their policy making procedures.

Institutions must work to reestablish the public trust in science. That is a challenge because while many amazing scientific advances have occurred (i.e., my MRI last week showed far more going on than my orthopedist and physical therapist detected based on clinical exam). Imaging such as MR and ultrasound have been major advances in diagnostic medicine, but there are also repeated examples demonstrating where medicine has been wrong. In the past 6 months I have read new guidelines for ear tubes, for neonatal jaundice, for newborn sepsis, and for newborn hypoglycemia. All indicate to me that my training 30 years ago was on target and the interval “improvements” in practice have been worthless Brownian motion based on false scientific discoveries. My recommendation would be that pediatrics do one-third as much research but do that research three times better and get it right.

Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@mdedge.com.

Get the science right. I have spent years researching and reflecting on what makes the best physicians, the best medicine, the optimal organized medical system, and the best medical ethics and law to support all of it. I have traveled to almost innumerable conferences to discuss these topics with colleagues who have similar goals. Time and time again, I come back to the conclusion that, in the modern era, the second-most important thing to do is to get the science right.

The practice of medicine in my Western world can be traced back to Hippocrates and earlier. The practice of nursing has other milestones. The healing arts have different points of origin in other cultures, such as China. In a modern world of mass communication, these various historical paths are converging on scientific evidence. The science to support medicine has always had flaws, but it has fared better than the other options. Sometimes, the science was so sketchy that the key was to believe in whatever the shaman was providing. But for the past 100 years, science, rather than tradition and hierarchy, has been relied upon to guide policy and action. For the past 50 years, evidence-based medicine has ascended. Have we become better than the snake oil salesmen of the late 19th century?

Modern health care is far from perfect. The pandemic has been a major stressor to the health care system. The pandemic has revealed flaws and weaknesses, including inequity in access to care, health illiteracy, and a shaky moral compass balancing individual liberty and social good. Overall, despite multiple mistakes dealing with a novel threat, I think the institutions promoting science have performed well during the pandemic, especially when compared with the moral and governmental institutions encouraging ethical behavior and making policies to promote justice.

My highest praise would be for the professionalism of health care workers. Nurses and physicians have staffed the hospitals and clinics caring for people when the hallways were overflowing for days without end. Without the commitment, the teamwork, and the courage to provide that care, the death toll would have been much higher and the suffering unimaginable. My observation is that these people were not motivated by an abstract primum non nocere, first do no harm. It was the commitment to love one’s neighbor and care for the sick. This dedication is the first most important thing in professionalism.

Part of what fuels that commitment is a belief that what they are doing makes a difference. The belief is stronger when there is measurable, scientific evidence that a difference is being made. The scientific decisions have not been perfect, but at this point the evidence is clear that the shutdown flattened the curve. Vaccines saved lives and will continue to do so. Masks saved lives. Nursing care, particularly intensive care, reduced the case fatality rate and assuaged suffering and grief.

What lessons about training new providers can be gleaned from the past 2 years? Those who teach professionalism for physicians, nurses, and other health care workers should strengthen the common value systems that undergird the commitment people have to the patients and the professions. In the face of postmodern nihilism and relativism, virtues need to be clarified and reinforced. In the face of political polarization which seeks to make a political affiliation the locus of loyalty and commitment, emphasize the fellowship of the health care professions.

To me as a scientist, a key lesson is that we need to be better at getting the science right. Two years ago I was wiping some groceries with alcohol and quarantining cans in shopping bags in the corner of the kitchen for 24 hours before shelving them. I still push elevator buttons with my knuckles. The Centers for Disease Control and Prevention needs to revamp their policy making procedures.

Institutions must work to reestablish the public trust in science. That is a challenge because while many amazing scientific advances have occurred (i.e., my MRI last week showed far more going on than my orthopedist and physical therapist detected based on clinical exam). Imaging such as MR and ultrasound have been major advances in diagnostic medicine, but there are also repeated examples demonstrating where medicine has been wrong. In the past 6 months I have read new guidelines for ear tubes, for neonatal jaundice, for newborn sepsis, and for newborn hypoglycemia. All indicate to me that my training 30 years ago was on target and the interval “improvements” in practice have been worthless Brownian motion based on false scientific discoveries. My recommendation would be that pediatrics do one-third as much research but do that research three times better and get it right.

Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@mdedge.com.

Get the science right. I have spent years researching and reflecting on what makes the best physicians, the best medicine, the optimal organized medical system, and the best medical ethics and law to support all of it. I have traveled to almost innumerable conferences to discuss these topics with colleagues who have similar goals. Time and time again, I come back to the conclusion that, in the modern era, the second-most important thing to do is to get the science right.

The practice of medicine in my Western world can be traced back to Hippocrates and earlier. The practice of nursing has other milestones. The healing arts have different points of origin in other cultures, such as China. In a modern world of mass communication, these various historical paths are converging on scientific evidence. The science to support medicine has always had flaws, but it has fared better than the other options. Sometimes, the science was so sketchy that the key was to believe in whatever the shaman was providing. But for the past 100 years, science, rather than tradition and hierarchy, has been relied upon to guide policy and action. For the past 50 years, evidence-based medicine has ascended. Have we become better than the snake oil salesmen of the late 19th century?

Modern health care is far from perfect. The pandemic has been a major stressor to the health care system. The pandemic has revealed flaws and weaknesses, including inequity in access to care, health illiteracy, and a shaky moral compass balancing individual liberty and social good. Overall, despite multiple mistakes dealing with a novel threat, I think the institutions promoting science have performed well during the pandemic, especially when compared with the moral and governmental institutions encouraging ethical behavior and making policies to promote justice.

My highest praise would be for the professionalism of health care workers. Nurses and physicians have staffed the hospitals and clinics caring for people when the hallways were overflowing for days without end. Without the commitment, the teamwork, and the courage to provide that care, the death toll would have been much higher and the suffering unimaginable. My observation is that these people were not motivated by an abstract primum non nocere, first do no harm. It was the commitment to love one’s neighbor and care for the sick. This dedication is the first most important thing in professionalism.

Part of what fuels that commitment is a belief that what they are doing makes a difference. The belief is stronger when there is measurable, scientific evidence that a difference is being made. The scientific decisions have not been perfect, but at this point the evidence is clear that the shutdown flattened the curve. Vaccines saved lives and will continue to do so. Masks saved lives. Nursing care, particularly intensive care, reduced the case fatality rate and assuaged suffering and grief.

What lessons about training new providers can be gleaned from the past 2 years? Those who teach professionalism for physicians, nurses, and other health care workers should strengthen the common value systems that undergird the commitment people have to the patients and the professions. In the face of postmodern nihilism and relativism, virtues need to be clarified and reinforced. In the face of political polarization which seeks to make a political affiliation the locus of loyalty and commitment, emphasize the fellowship of the health care professions.

To me as a scientist, a key lesson is that we need to be better at getting the science right. Two years ago I was wiping some groceries with alcohol and quarantining cans in shopping bags in the corner of the kitchen for 24 hours before shelving them. I still push elevator buttons with my knuckles. The Centers for Disease Control and Prevention needs to revamp their policy making procedures.

Institutions must work to reestablish the public trust in science. That is a challenge because while many amazing scientific advances have occurred (i.e., my MRI last week showed far more going on than my orthopedist and physical therapist detected based on clinical exam). Imaging such as MR and ultrasound have been major advances in diagnostic medicine, but there are also repeated examples demonstrating where medicine has been wrong. In the past 6 months I have read new guidelines for ear tubes, for neonatal jaundice, for newborn sepsis, and for newborn hypoglycemia. All indicate to me that my training 30 years ago was on target and the interval “improvements” in practice have been worthless Brownian motion based on false scientific discoveries. My recommendation would be that pediatrics do one-third as much research but do that research three times better and get it right.

Dr. Powell is a retired pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at pdnews@mdedge.com.

The Diagnosis: Odontogenic Cutaneous Sinus Tract

In our patient, panoramic radiography showed a radiolucency in the periapex of the mandibular first molar (Figure 1). Ultrasonography depicted a hypoechoic band that originated from the cutaneous lesion and extended through the subcutaneous tissue to the defective alveolar bone, suggesting odontogenic inflammation (Figure 2).¹ The infected pulp was removed, and the purulent nodules then disappeared.

The dental etiology of odontogenic cutaneous sinus tracts can be confirmed by panoramic radiography and ultrasonography. The odontogenic sinus path can be clearly observed via radiography by injecting or inserting a radiopaque substance into the sinus tract.² Effective treatment of the diseased tooth is removal of the infected pulp, performance of a root canal to eliminate infection, closure and filling of the root canal, and repair of the crown. Once the source of infection is eliminated, the sinus typically subsides within 2 weeks. When residual skin retreats or scars are present, cosmetic surgery can be performed to improve the appearance.^3,4

Odontogenic cutaneous sinus tracts usually are caused by a route of drainage from a chronic apical abscess. They follow a path of least resistance through the alveolar bone and periosteum, spreading into the surrounding soft tissues. With the formation of abscesses, sinus tracts will erupt intraorally or cutaneously, depending on the relationship of the posterior tooth apices to the mandibular attachments of the mylohyoid and buccinator muscles and the maxillary attachment of the buccinator.^2,5 Clinically, cutaneous lesions present as nodules, cysts, or dimples that have attached to deep tissues through the sinus tract. Half of patients may have no dental symptoms and often are misdiagnosed with nonodontogenic lesions. Subsequent improper treatments, such as repeated use of antibiotics, multiple biopsies, surgical excision, and chemotherapy, often are repeated and ineffective.⁶ The most common cause of chronic cutaneous sinus tracts in the face and neck is a chronically draining dental infection.^2,5 A thorough history is necessary when odontogenic cutaneous sinuses are suspected. Toothache before the development of the sinus tract is an important diagnostic clue.

Pyogenic granuloma, syringocystadenoma papilliferum, osteomyelitis, infected epidermoid cyst, actinomycoses, and salivary gland fistula also should be considered in the differential diagnosis.^7-10 Pyogenic granuloma (also known as lobular capillary hemangioma) is a benign overgrowth of capillaries showing a vascular phenotype that usually occurs as a response to different stimulating factors such as local stimuli, trauma, or hormonal factors. Clinically, pyogenic granuloma presents as a red, solitary, painless nodule on the face or distal extremities.^11,12 Syringocystadenoma papilliferum is a benign adnexal proliferation with apocrine differentiation that usually presents as a hairless papillomatous plaque or nodule measuring 1 to 4 cm in diameter and often is first noted at birth or during early childhood.⁷ Osteomyelitis is progressive inflammation of the periosteum and bone marrow that rapidly breaks through the periosteum and spreads to surrounding areas. The mandible is the most susceptible bone for facial osteomyelitis.⁸ Epidermoid cysts are formed by the proliferation of epidermal cells within a circumscribed dermal space. Infection of the cysts is characterized by redness, swelling, heat, and pain. As the infection progresses, suppurative inflammation develops, leading to local liquefaction and abscesses.⁹

This case was initially misdiagnosed as infectious skin lesions by outside clinicians. Multiple surgical treatments and long-term antibiotic therapy were attempted before the correct diagnosis was made. The clinical diagnosis of odontogenic cutaneous sinus tracts is challenging due to the variety of affected sites and clinical signs. Ultrasonography should be performed as early as possible to identify the disease and avoid unnecessary surgery. For appropriate dental therapy, close liaison with the stomatology department is warranted.

The Diagnosis: Odontogenic Cutaneous Sinus Tract

In our patient, panoramic radiography showed a radiolucency in the periapex of the mandibular first molar (Figure 1). Ultrasonography depicted a hypoechoic band that originated from the cutaneous lesion and extended through the subcutaneous tissue to the defective alveolar bone, suggesting odontogenic inflammation (Figure 2).¹ The infected pulp was removed, and the purulent nodules then disappeared.

The dental etiology of odontogenic cutaneous sinus tracts can be confirmed by panoramic radiography and ultrasonography. The odontogenic sinus path can be clearly observed via radiography by injecting or inserting a radiopaque substance into the sinus tract.² Effective treatment of the diseased tooth is removal of the infected pulp, performance of a root canal to eliminate infection, closure and filling of the root canal, and repair of the crown. Once the source of infection is eliminated, the sinus typically subsides within 2 weeks. When residual skin retreats or scars are present, cosmetic surgery can be performed to improve the appearance.^3,4

Odontogenic cutaneous sinus tracts usually are caused by a route of drainage from a chronic apical abscess. They follow a path of least resistance through the alveolar bone and periosteum, spreading into the surrounding soft tissues. With the formation of abscesses, sinus tracts will erupt intraorally or cutaneously, depending on the relationship of the posterior tooth apices to the mandibular attachments of the mylohyoid and buccinator muscles and the maxillary attachment of the buccinator.^2,5 Clinically, cutaneous lesions present as nodules, cysts, or dimples that have attached to deep tissues through the sinus tract. Half of patients may have no dental symptoms and often are misdiagnosed with nonodontogenic lesions. Subsequent improper treatments, such as repeated use of antibiotics, multiple biopsies, surgical excision, and chemotherapy, often are repeated and ineffective.⁶ The most common cause of chronic cutaneous sinus tracts in the face and neck is a chronically draining dental infection.^2,5 A thorough history is necessary when odontogenic cutaneous sinuses are suspected. Toothache before the development of the sinus tract is an important diagnostic clue.

Pyogenic granuloma, syringocystadenoma papilliferum, osteomyelitis, infected epidermoid cyst, actinomycoses, and salivary gland fistula also should be considered in the differential diagnosis.^7-10 Pyogenic granuloma (also known as lobular capillary hemangioma) is a benign overgrowth of capillaries showing a vascular phenotype that usually occurs as a response to different stimulating factors such as local stimuli, trauma, or hormonal factors. Clinically, pyogenic granuloma presents as a red, solitary, painless nodule on the face or distal extremities.^11,12 Syringocystadenoma papilliferum is a benign adnexal proliferation with apocrine differentiation that usually presents as a hairless papillomatous plaque or nodule measuring 1 to 4 cm in diameter and often is first noted at birth or during early childhood.⁷ Osteomyelitis is progressive inflammation of the periosteum and bone marrow that rapidly breaks through the periosteum and spreads to surrounding areas. The mandible is the most susceptible bone for facial osteomyelitis.⁸ Epidermoid cysts are formed by the proliferation of epidermal cells within a circumscribed dermal space. Infection of the cysts is characterized by redness, swelling, heat, and pain. As the infection progresses, suppurative inflammation develops, leading to local liquefaction and abscesses.⁹

This case was initially misdiagnosed as infectious skin lesions by outside clinicians. Multiple surgical treatments and long-term antibiotic therapy were attempted before the correct diagnosis was made. The clinical diagnosis of odontogenic cutaneous sinus tracts is challenging due to the variety of affected sites and clinical signs. Ultrasonography should be performed as early as possible to identify the disease and avoid unnecessary surgery. For appropriate dental therapy, close liaison with the stomatology department is warranted.

The Diagnosis: Odontogenic Cutaneous Sinus Tract

In our patient, panoramic radiography showed a radiolucency in the periapex of the mandibular first molar (Figure 1). Ultrasonography depicted a hypoechoic band that originated from the cutaneous lesion and extended through the subcutaneous tissue to the defective alveolar bone, suggesting odontogenic inflammation (Figure 2).¹ The infected pulp was removed, and the purulent nodules then disappeared.

The dental etiology of odontogenic cutaneous sinus tracts can be confirmed by panoramic radiography and ultrasonography. The odontogenic sinus path can be clearly observed via radiography by injecting or inserting a radiopaque substance into the sinus tract.² Effective treatment of the diseased tooth is removal of the infected pulp, performance of a root canal to eliminate infection, closure and filling of the root canal, and repair of the crown. Once the source of infection is eliminated, the sinus typically subsides within 2 weeks. When residual skin retreats or scars are present, cosmetic surgery can be performed to improve the appearance.^3,4

Odontogenic cutaneous sinus tracts usually are caused by a route of drainage from a chronic apical abscess. They follow a path of least resistance through the alveolar bone and periosteum, spreading into the surrounding soft tissues. With the formation of abscesses, sinus tracts will erupt intraorally or cutaneously, depending on the relationship of the posterior tooth apices to the mandibular attachments of the mylohyoid and buccinator muscles and the maxillary attachment of the buccinator.^2,5 Clinically, cutaneous lesions present as nodules, cysts, or dimples that have attached to deep tissues through the sinus tract. Half of patients may have no dental symptoms and often are misdiagnosed with nonodontogenic lesions. Subsequent improper treatments, such as repeated use of antibiotics, multiple biopsies, surgical excision, and chemotherapy, often are repeated and ineffective.⁶ The most common cause of chronic cutaneous sinus tracts in the face and neck is a chronically draining dental infection.^2,5 A thorough history is necessary when odontogenic cutaneous sinuses are suspected. Toothache before the development of the sinus tract is an important diagnostic clue.

Pyogenic granuloma, syringocystadenoma papilliferum, osteomyelitis, infected epidermoid cyst, actinomycoses, and salivary gland fistula also should be considered in the differential diagnosis.^7-10 Pyogenic granuloma (also known as lobular capillary hemangioma) is a benign overgrowth of capillaries showing a vascular phenotype that usually occurs as a response to different stimulating factors such as local stimuli, trauma, or hormonal factors. Clinically, pyogenic granuloma presents as a red, solitary, painless nodule on the face or distal extremities.^11,12 Syringocystadenoma papilliferum is a benign adnexal proliferation with apocrine differentiation that usually presents as a hairless papillomatous plaque or nodule measuring 1 to 4 cm in diameter and often is first noted at birth or during early childhood.⁷ Osteomyelitis is progressive inflammation of the periosteum and bone marrow that rapidly breaks through the periosteum and spreads to surrounding areas. The mandible is the most susceptible bone for facial osteomyelitis.⁸ Epidermoid cysts are formed by the proliferation of epidermal cells within a circumscribed dermal space. Infection of the cysts is characterized by redness, swelling, heat, and pain. As the infection progresses, suppurative inflammation develops, leading to local liquefaction and abscesses.⁹

This case was initially misdiagnosed as infectious skin lesions by outside clinicians. Multiple surgical treatments and long-term antibiotic therapy were attempted before the correct diagnosis was made. The clinical diagnosis of odontogenic cutaneous sinus tracts is challenging due to the variety of affected sites and clinical signs. Ultrasonography should be performed as early as possible to identify the disease and avoid unnecessary surgery. For appropriate dental therapy, close liaison with the stomatology department is warranted.

In February, citing the need for more data, Pfizer and BioNTech announced that they were delaying the application for their COVID-19 vaccine for children under the age of 5. Earlier evidence suggests that two doses may not provide adequate protection in the 2- to 4-year old age group. With the larger number of infections and illness in the younger age group from the Omicron variant, Pfizer and BioNTech felt they needed more data on the effectiveness of a third dose.

This delay came as a disappointment to parents of children under 5 who have been eager to have them receive the vaccination. However, Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the Food and Drug Administration, told parents that this delay should be reassuring – that the companies were doing important due diligence before releasing a product that is both safe and effective. The American Academy of Pediatrics wisely released a similar statement of reassurance and support.

It is difficult to know how many parents will eventually immunize their young children once the vaccine is approved. Any survey done more than a few weeks ago must be viewed cautiously as “the COVID numbers” around the country continue to improve and parental attitudes are likely to change.

There will always remain subgroups of parents on either extreme of the bell-shaped curve. Some will reject the under-5 vaccine simply because it is a vaccine. Some parents are so anxious to vaccinate that they will want to be first in line even if waiting is the more prudent approach. In a recent opinion piece appearing in the New York Times, a statistician writes that he is so eager to have his young children immunized that he is encouraging the FDA to replace its traditional reliance on “statistical significance” with a less rigid and binary method such as one based on Bayesian theory (Aubrey Carlton, “I’m a parent and a statistician. There’s a smarter way to think about the under-5 vaccine.” The New York Times. 2022 Mar 1.). However, what this statistician misses in his haste to vaccinate his own children is that we are dealing with an entire population with varying levels of scientific sophistication and appetite for risk. While “statistical significance” may no longer be cutting edge to some statisticians, most of the rest of the country finds the term reassuring.

It will be interesting to see what happens if and when the vaccine is approved. Will the American Academy of Pediatrics come out with a strong recommendation? I hope they are careful and provide a sufficient number of caveats, otherwise we in the trenches will again be left to provide more nuanced advice to families who are both anxious and hesitant.

Despite the recent surge in cases among young children, apparently as a result of the Omicron variant, the disease continues to cause less and milder disease among young children than it does in adults. And the degree to which illness in the pediatric population contributes to the health of the general population appears to still be a matter of debate. This may be yet another instance of when the crafty COVID-19 has moved with a pace that will make an under–age-5 vaccine of relatively little value.

First, we must be careful to assure ourselves that any side effects the vaccine might generate are well within an even more restricted acceptable range. Second, we must be careful not to squander our persuasive currency by promoting a vaccine that in retrospect may turn out to be of relatively little value.

Although there is ample evidence that education often fails to convince the committed anti-vaxxers, pediatricians continue to be held in high regard by most parents, many of whom are understandably confused by the tsunami of health information of mixed quality generated by the pandemic. We must be cautious not to cast ourselves as a group whose knee-jerk reaction is to recommend every vaccine with equal vigor. All vaccines are not created equal. We must be patient and prepared to adjust the level of our enthusiasm. We must continue to tailor our advice based on the hard data. Otherwise, parents will stop asking for our advice because they will believe that they already know what we’re going to say.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

In February, citing the need for more data, Pfizer and BioNTech announced that they were delaying the application for their COVID-19 vaccine for children under the age of 5. Earlier evidence suggests that two doses may not provide adequate protection in the 2- to 4-year old age group. With the larger number of infections and illness in the younger age group from the Omicron variant, Pfizer and BioNTech felt they needed more data on the effectiveness of a third dose.

This delay came as a disappointment to parents of children under 5 who have been eager to have them receive the vaccination. However, Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the Food and Drug Administration, told parents that this delay should be reassuring – that the companies were doing important due diligence before releasing a product that is both safe and effective. The American Academy of Pediatrics wisely released a similar statement of reassurance and support.

It is difficult to know how many parents will eventually immunize their young children once the vaccine is approved. Any survey done more than a few weeks ago must be viewed cautiously as “the COVID numbers” around the country continue to improve and parental attitudes are likely to change.

There will always remain subgroups of parents on either extreme of the bell-shaped curve. Some will reject the under-5 vaccine simply because it is a vaccine. Some parents are so anxious to vaccinate that they will want to be first in line even if waiting is the more prudent approach. In a recent opinion piece appearing in the New York Times, a statistician writes that he is so eager to have his young children immunized that he is encouraging the FDA to replace its traditional reliance on “statistical significance” with a less rigid and binary method such as one based on Bayesian theory (Aubrey Carlton, “I’m a parent and a statistician. There’s a smarter way to think about the under-5 vaccine.” The New York Times. 2022 Mar 1.). However, what this statistician misses in his haste to vaccinate his own children is that we are dealing with an entire population with varying levels of scientific sophistication and appetite for risk. While “statistical significance” may no longer be cutting edge to some statisticians, most of the rest of the country finds the term reassuring.

It will be interesting to see what happens if and when the vaccine is approved. Will the American Academy of Pediatrics come out with a strong recommendation? I hope they are careful and provide a sufficient number of caveats, otherwise we in the trenches will again be left to provide more nuanced advice to families who are both anxious and hesitant.

Despite the recent surge in cases among young children, apparently as a result of the Omicron variant, the disease continues to cause less and milder disease among young children than it does in adults. And the degree to which illness in the pediatric population contributes to the health of the general population appears to still be a matter of debate. This may be yet another instance of when the crafty COVID-19 has moved with a pace that will make an under–age-5 vaccine of relatively little value.

First, we must be careful to assure ourselves that any side effects the vaccine might generate are well within an even more restricted acceptable range. Second, we must be careful not to squander our persuasive currency by promoting a vaccine that in retrospect may turn out to be of relatively little value.

Although there is ample evidence that education often fails to convince the committed anti-vaxxers, pediatricians continue to be held in high regard by most parents, many of whom are understandably confused by the tsunami of health information of mixed quality generated by the pandemic. We must be cautious not to cast ourselves as a group whose knee-jerk reaction is to recommend every vaccine with equal vigor. All vaccines are not created equal. We must be patient and prepared to adjust the level of our enthusiasm. We must continue to tailor our advice based on the hard data. Otherwise, parents will stop asking for our advice because they will believe that they already know what we’re going to say.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

In February, citing the need for more data, Pfizer and BioNTech announced that they were delaying the application for their COVID-19 vaccine for children under the age of 5. Earlier evidence suggests that two doses may not provide adequate protection in the 2- to 4-year old age group. With the larger number of infections and illness in the younger age group from the Omicron variant, Pfizer and BioNTech felt they needed more data on the effectiveness of a third dose.

This delay came as a disappointment to parents of children under 5 who have been eager to have them receive the vaccination. However, Peter Marks, MD, director of the Center for Biologics Evaluation and Research at the Food and Drug Administration, told parents that this delay should be reassuring – that the companies were doing important due diligence before releasing a product that is both safe and effective. The American Academy of Pediatrics wisely released a similar statement of reassurance and support.

It is difficult to know how many parents will eventually immunize their young children once the vaccine is approved. Any survey done more than a few weeks ago must be viewed cautiously as “the COVID numbers” around the country continue to improve and parental attitudes are likely to change.

There will always remain subgroups of parents on either extreme of the bell-shaped curve. Some will reject the under-5 vaccine simply because it is a vaccine. Some parents are so anxious to vaccinate that they will want to be first in line even if waiting is the more prudent approach. In a recent opinion piece appearing in the New York Times, a statistician writes that he is so eager to have his young children immunized that he is encouraging the FDA to replace its traditional reliance on “statistical significance” with a less rigid and binary method such as one based on Bayesian theory (Aubrey Carlton, “I’m a parent and a statistician. There’s a smarter way to think about the under-5 vaccine.” The New York Times. 2022 Mar 1.). However, what this statistician misses in his haste to vaccinate his own children is that we are dealing with an entire population with varying levels of scientific sophistication and appetite for risk. While “statistical significance” may no longer be cutting edge to some statisticians, most of the rest of the country finds the term reassuring.

It will be interesting to see what happens if and when the vaccine is approved. Will the American Academy of Pediatrics come out with a strong recommendation? I hope they are careful and provide a sufficient number of caveats, otherwise we in the trenches will again be left to provide more nuanced advice to families who are both anxious and hesitant.

Despite the recent surge in cases among young children, apparently as a result of the Omicron variant, the disease continues to cause less and milder disease among young children than it does in adults. And the degree to which illness in the pediatric population contributes to the health of the general population appears to still be a matter of debate. This may be yet another instance of when the crafty COVID-19 has moved with a pace that will make an under–age-5 vaccine of relatively little value.

First, we must be careful to assure ourselves that any side effects the vaccine might generate are well within an even more restricted acceptable range. Second, we must be careful not to squander our persuasive currency by promoting a vaccine that in retrospect may turn out to be of relatively little value.

Although there is ample evidence that education often fails to convince the committed anti-vaxxers, pediatricians continue to be held in high regard by most parents, many of whom are understandably confused by the tsunami of health information of mixed quality generated by the pandemic. We must be cautious not to cast ourselves as a group whose knee-jerk reaction is to recommend every vaccine with equal vigor. All vaccines are not created equal. We must be patient and prepared to adjust the level of our enthusiasm. We must continue to tailor our advice based on the hard data. Otherwise, parents will stop asking for our advice because they will believe that they already know what we’re going to say.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

A 6-month-old boy presented with 2 days of looser-than-normal stools without blood or mucous. Before the onset of diarrhea, he had been fed at least two bottles of an infant formula identified in a national recall. His mom requested testing for Cronobacter sakazakii.

In mid-February, Abbott Nutrition recalled specific lots of powdered formula produced at one Michigan manufacturing facility because of possible Cronobacter contamination. To date, a public health investigation has identified four infants in three states who developed Cronobacter infection after consuming formula that was part of the recall. Two of the infants died.

As media reports urged families to search their kitchens for containers of the implicated formula and return them for a refund, worried parents reached out to pediatric care providers for advice.

Cronobacter sakazakii and other Cronobacter species are Gram-negative environmental organisms that occasionally cause bacteremia and meningitis in young infants. Although these infections are not subject to mandatory reporting in most states, laboratory-based surveillance suggests that 18 cases occur annually in the United States (0.49 cases/100,00 infants).

While early reports in the literature described cases in hospitalized, preterm infants, infections also occur in the community and in children born at or near term. A Centers for Disease Control and Prevention review of domestic and international cases identified 183 children <12 months of age between 1961 and 2018 described as diagnosed with Cronobacter bacteremia or meningitis.¹ Of the 79 U.S. cases, 34 occurred in term infants and 50 were community onset. Most cases occurred in the first month of life; the oldest child was 35 days of age at the onset of symptoms. Meningitis was more likely in infants born close to term and who were not hospitalized at the time of infection. The majority of infants for whom a feeding history was available had consumed powdered formula.

Back in the exam room, the 6-month-old was examined and found to be vigorous and well-appearing with normal vital signs and no signs of dehydration. The infant’s pediatrician found no clinical indication to perform a blood culture or lumbar puncture, the tests used to diagnose invasive Cronobacter infection. She explained that stool cultures are not recommended, as Cronobacter does not usually cause diarrhea in infants and finding the bacteria in the stool may represent colonization rather than infection.

The pediatrician did take the opportunity to talk to the mom about her formula preparation practices and shared a handout. Powdered formula isn’t sterile, but it is safe for most infants when prepared according to manufacturer’s directions. Contamination of formula during or after preparation can also result in Cronobacter infection in vulnerable infants.

The mom was surprised – and unhappy – to learn that Cronobacter could be lurking in her kitchen. More than a decade ago, investigators visited 78 households in Tennessee and cultured multiple kitchen surfaces.²C. sakazakii was recovered from 21 homes. Most of the positive cultures were from sinks, counter tops, and used dishcloths. Cronobacter has also been cultured from a variety of dried food items, including powdered milk, herbal tea, and starches.

According to the CDC, liquid formula, a product that is sterile until opened, is a safer choice for formula-fed infants who are less than 3 months of age, were born prematurely, or have a compromised immune system. When these infants must be fed powdered formula, preparing it with water heated to at least 158°F or 70°C can kill Cronobacter organisms. Parents should be instructed to boil water and let it cool for about 5 minutes before using it to mix formula.

While most cases of Cronobacter in infants have been epidemiologically linked to consumption of powdered formula, sporadic case reports describe infection in infants fed expressed breast milk. In one report, identical bacterial isolates were recovered from expressed milk fed to an infected infant and the breast pump used to express the milk.³

Moms who express milk should be instructed in proper breast pump hygiene, including washing hands thoroughly before handling breast pumps; disassembling and cleaning breast pumps kits after each use, either in hot soapy water with a dedicated brush and basin or in the dishwasher; air drying on a clean surface; and sanitizing at least daily by boiling, steaming, or using a dishwasher’s sanitize cycle.

Health care providers are encouraged to report Cronobacter cases to their state or local health departments.

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.

References

1. Strysko J et al. Emerg Infect Dis. 2020;26(5):857-65.

2. Kilonzo-Nthenge A et al. J Food Protect 2012;75(8):1512-7.

3. Bowen A et al. MMWR Morb Mortal Wkly Rep. 2017;66:761-2.

A 6-month-old boy presented with 2 days of looser-than-normal stools without blood or mucous. Before the onset of diarrhea, he had been fed at least two bottles of an infant formula identified in a national recall. His mom requested testing for Cronobacter sakazakii.

In mid-February, Abbott Nutrition recalled specific lots of powdered formula produced at one Michigan manufacturing facility because of possible Cronobacter contamination. To date, a public health investigation has identified four infants in three states who developed Cronobacter infection after consuming formula that was part of the recall. Two of the infants died.

As media reports urged families to search their kitchens for containers of the implicated formula and return them for a refund, worried parents reached out to pediatric care providers for advice.

Cronobacter sakazakii and other Cronobacter species are Gram-negative environmental organisms that occasionally cause bacteremia and meningitis in young infants. Although these infections are not subject to mandatory reporting in most states, laboratory-based surveillance suggests that 18 cases occur annually in the United States (0.49 cases/100,00 infants).

While early reports in the literature described cases in hospitalized, preterm infants, infections also occur in the community and in children born at or near term. A Centers for Disease Control and Prevention review of domestic and international cases identified 183 children <12 months of age between 1961 and 2018 described as diagnosed with Cronobacter bacteremia or meningitis.¹ Of the 79 U.S. cases, 34 occurred in term infants and 50 were community onset. Most cases occurred in the first month of life; the oldest child was 35 days of age at the onset of symptoms. Meningitis was more likely in infants born close to term and who were not hospitalized at the time of infection. The majority of infants for whom a feeding history was available had consumed powdered formula.

Back in the exam room, the 6-month-old was examined and found to be vigorous and well-appearing with normal vital signs and no signs of dehydration. The infant’s pediatrician found no clinical indication to perform a blood culture or lumbar puncture, the tests used to diagnose invasive Cronobacter infection. She explained that stool cultures are not recommended, as Cronobacter does not usually cause diarrhea in infants and finding the bacteria in the stool may represent colonization rather than infection.

The pediatrician did take the opportunity to talk to the mom about her formula preparation practices and shared a handout. Powdered formula isn’t sterile, but it is safe for most infants when prepared according to manufacturer’s directions. Contamination of formula during or after preparation can also result in Cronobacter infection in vulnerable infants.

The mom was surprised – and unhappy – to learn that Cronobacter could be lurking in her kitchen. More than a decade ago, investigators visited 78 households in Tennessee and cultured multiple kitchen surfaces.²C. sakazakii was recovered from 21 homes. Most of the positive cultures were from sinks, counter tops, and used dishcloths. Cronobacter has also been cultured from a variety of dried food items, including powdered milk, herbal tea, and starches.

According to the CDC, liquid formula, a product that is sterile until opened, is a safer choice for formula-fed infants who are less than 3 months of age, were born prematurely, or have a compromised immune system. When these infants must be fed powdered formula, preparing it with water heated to at least 158°F or 70°C can kill Cronobacter organisms. Parents should be instructed to boil water and let it cool for about 5 minutes before using it to mix formula.

While most cases of Cronobacter in infants have been epidemiologically linked to consumption of powdered formula, sporadic case reports describe infection in infants fed expressed breast milk. In one report, identical bacterial isolates were recovered from expressed milk fed to an infected infant and the breast pump used to express the milk.³

Moms who express milk should be instructed in proper breast pump hygiene, including washing hands thoroughly before handling breast pumps; disassembling and cleaning breast pumps kits after each use, either in hot soapy water with a dedicated brush and basin or in the dishwasher; air drying on a clean surface; and sanitizing at least daily by boiling, steaming, or using a dishwasher’s sanitize cycle.

Health care providers are encouraged to report Cronobacter cases to their state or local health departments.

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.

References

1. Strysko J et al. Emerg Infect Dis. 2020;26(5):857-65.

2. Kilonzo-Nthenge A et al. J Food Protect 2012;75(8):1512-7.

3. Bowen A et al. MMWR Morb Mortal Wkly Rep. 2017;66:761-2.

A 6-month-old boy presented with 2 days of looser-than-normal stools without blood or mucous. Before the onset of diarrhea, he had been fed at least two bottles of an infant formula identified in a national recall. His mom requested testing for Cronobacter sakazakii.

In mid-February, Abbott Nutrition recalled specific lots of powdered formula produced at one Michigan manufacturing facility because of possible Cronobacter contamination. To date, a public health investigation has identified four infants in three states who developed Cronobacter infection after consuming formula that was part of the recall. Two of the infants died.

As media reports urged families to search their kitchens for containers of the implicated formula and return them for a refund, worried parents reached out to pediatric care providers for advice.

Cronobacter sakazakii and other Cronobacter species are Gram-negative environmental organisms that occasionally cause bacteremia and meningitis in young infants. Although these infections are not subject to mandatory reporting in most states, laboratory-based surveillance suggests that 18 cases occur annually in the United States (0.49 cases/100,00 infants).

While early reports in the literature described cases in hospitalized, preterm infants, infections also occur in the community and in children born at or near term. A Centers for Disease Control and Prevention review of domestic and international cases identified 183 children <12 months of age between 1961 and 2018 described as diagnosed with Cronobacter bacteremia or meningitis.¹ Of the 79 U.S. cases, 34 occurred in term infants and 50 were community onset. Most cases occurred in the first month of life; the oldest child was 35 days of age at the onset of symptoms. Meningitis was more likely in infants born close to term and who were not hospitalized at the time of infection. The majority of infants for whom a feeding history was available had consumed powdered formula.

Back in the exam room, the 6-month-old was examined and found to be vigorous and well-appearing with normal vital signs and no signs of dehydration. The infant’s pediatrician found no clinical indication to perform a blood culture or lumbar puncture, the tests used to diagnose invasive Cronobacter infection. She explained that stool cultures are not recommended, as Cronobacter does not usually cause diarrhea in infants and finding the bacteria in the stool may represent colonization rather than infection.

The pediatrician did take the opportunity to talk to the mom about her formula preparation practices and shared a handout. Powdered formula isn’t sterile, but it is safe for most infants when prepared according to manufacturer’s directions. Contamination of formula during or after preparation can also result in Cronobacter infection in vulnerable infants.

The mom was surprised – and unhappy – to learn that Cronobacter could be lurking in her kitchen. More than a decade ago, investigators visited 78 households in Tennessee and cultured multiple kitchen surfaces.²C. sakazakii was recovered from 21 homes. Most of the positive cultures were from sinks, counter tops, and used dishcloths. Cronobacter has also been cultured from a variety of dried food items, including powdered milk, herbal tea, and starches.

According to the CDC, liquid formula, a product that is sterile until opened, is a safer choice for formula-fed infants who are less than 3 months of age, were born prematurely, or have a compromised immune system. When these infants must be fed powdered formula, preparing it with water heated to at least 158°F or 70°C can kill Cronobacter organisms. Parents should be instructed to boil water and let it cool for about 5 minutes before using it to mix formula.

While most cases of Cronobacter in infants have been epidemiologically linked to consumption of powdered formula, sporadic case reports describe infection in infants fed expressed breast milk. In one report, identical bacterial isolates were recovered from expressed milk fed to an infected infant and the breast pump used to express the milk.³

Moms who express milk should be instructed in proper breast pump hygiene, including washing hands thoroughly before handling breast pumps; disassembling and cleaning breast pumps kits after each use, either in hot soapy water with a dedicated brush and basin or in the dishwasher; air drying on a clean surface; and sanitizing at least daily by boiling, steaming, or using a dishwasher’s sanitize cycle.

Health care providers are encouraged to report Cronobacter cases to their state or local health departments.

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at pdnews@mdedge.com.

References

1. Strysko J et al. Emerg Infect Dis. 2020;26(5):857-65.

2. Kilonzo-Nthenge A et al. J Food Protect 2012;75(8):1512-7.

3. Bowen A et al. MMWR Morb Mortal Wkly Rep. 2017;66:761-2.

Scientists are trying different approaches to developing vaccines against norovirus, seeking to replicate the success seen in developing shots against rotavirus.

Speaking at the 12th World Congress of the World Society for Pediatric Infectious Diseases (WSPID), Miguel O’Ryan, MD, of the University of Chile, Santiago, presented an overview of candidate vaccines. Dr. O’Ryan has been involved for many years with research on rotavirus vaccines and has branched into work with the somewhat similar norovirus.

With advances in preventing rotavirus, norovirus has emerged in recent years as a leading cause of acute gastroenteritis (AGE) in most countries worldwide. It’s associated with almost 20% of all acute diarrheal cases globally and with an estimated 685 million episodes and 212,000 deaths annually, Dr. O’Ryan and coauthors reported in a review in the journal Viruses.

If successful, norovirus vaccines may be used someday to prevent outbreaks among military personnel, as this contagious virus has the potential to disrupt missions, Dr. O’Ryan and coauthors wrote. They also said people might consider getting norovirus vaccines ahead of trips to prevent traveler’s diarrhea. But most importantly, these kinds of vaccines could reduce diarrhea-associated hospitalizations and deaths of children. 

Takeda Pharmaceutical Company, for whom Dr. O’Ryan has done consulting, last year announced a collaboration with Frazier Healthcare Partners to launch HilleVax. Based in Boston, the company is intended to commercialize Takeda’s norovirus vaccine candidate.

The Takeda-HilleVax candidate vaccine injection has advanced as far as phase 2 studies, including a test done over two winter seasons in U.S. Navy recruits. Takeda and U.S. Navy scientists reported in 2020 in the journal Vaccine that the primary efficacy outcome for this test could not be evaluated due to an unexpectedly low number of cases of norovirus. Still, data taken from this study indicate that the vaccine induces a broad immune response, the scientists reported.

In his WSPID presentation, Dr. O’Ryan also mentioned an oral norovirus vaccine candidate that the company Vaxart is developing, referring to this as a “very interesting approach.” 
 

Betting on the gut

Based in South San Francisco, California, Vaxart is pursuing a theory that a vaccine designed to generate mucosal antibodies locally in the intestine, in addition to systemic antibodies in the blood, may better protect against norovirus infection than an injectable vaccine.

“A key ability to protect against norovirus needs to come from an intestinal immune response, and injected vaccines don’t give those very well,” Sean Tucker, PhD, the founder and chief scientific officer of Vaxart, told this news organization in an interview. “We think that’s one of the reasons why our oral approaches can have significant advantages.”

Challenges to developing a norovirus vaccine have included a lack of good animal models to use in research and a lack of an ability to grow the virus well in cell culture, Dr. Tucker said.

Vaxart experienced disruptions in its research during the early stages of the pandemic but has since picked up the pace of its efforts to develop its oral vaccine, Dr. Tucker said during the interview.

In a recent filing with the Securities and Exchange Commission, Vaxart said in early 2021 it resumed its norovirus vaccine program by initiating three clinical studies. These included a phase 1b placebo-controlled dose ranging study in healthy elderly adults aged 55-80. Data from these trials may be unveiled in the coming months.

Vaxart said that this year it has already initiated a phase 2 norovirus challenge study, which will evaluate safety, immunogenicity, and clinical efficacy of a vaccine candidate against placebo.

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

Scientists are trying different approaches to developing vaccines against norovirus, seeking to replicate the success seen in developing shots against rotavirus.

Speaking at the 12th World Congress of the World Society for Pediatric Infectious Diseases (WSPID), Miguel O’Ryan, MD, of the University of Chile, Santiago, presented an overview of candidate vaccines. Dr. O’Ryan has been involved for many years with research on rotavirus vaccines and has branched into work with the somewhat similar norovirus.

With advances in preventing rotavirus, norovirus has emerged in recent years as a leading cause of acute gastroenteritis (AGE) in most countries worldwide. It’s associated with almost 20% of all acute diarrheal cases globally and with an estimated 685 million episodes and 212,000 deaths annually, Dr. O’Ryan and coauthors reported in a review in the journal Viruses.

If successful, norovirus vaccines may be used someday to prevent outbreaks among military personnel, as this contagious virus has the potential to disrupt missions, Dr. O’Ryan and coauthors wrote. They also said people might consider getting norovirus vaccines ahead of trips to prevent traveler’s diarrhea. But most importantly, these kinds of vaccines could reduce diarrhea-associated hospitalizations and deaths of children. 

Takeda Pharmaceutical Company, for whom Dr. O’Ryan has done consulting, last year announced a collaboration with Frazier Healthcare Partners to launch HilleVax. Based in Boston, the company is intended to commercialize Takeda’s norovirus vaccine candidate.

The Takeda-HilleVax candidate vaccine injection has advanced as far as phase 2 studies, including a test done over two winter seasons in U.S. Navy recruits. Takeda and U.S. Navy scientists reported in 2020 in the journal Vaccine that the primary efficacy outcome for this test could not be evaluated due to an unexpectedly low number of cases of norovirus. Still, data taken from this study indicate that the vaccine induces a broad immune response, the scientists reported.

In his WSPID presentation, Dr. O’Ryan also mentioned an oral norovirus vaccine candidate that the company Vaxart is developing, referring to this as a “very interesting approach.” 
 

Betting on the gut

Based in South San Francisco, California, Vaxart is pursuing a theory that a vaccine designed to generate mucosal antibodies locally in the intestine, in addition to systemic antibodies in the blood, may better protect against norovirus infection than an injectable vaccine.

“A key ability to protect against norovirus needs to come from an intestinal immune response, and injected vaccines don’t give those very well,” Sean Tucker, PhD, the founder and chief scientific officer of Vaxart, told this news organization in an interview. “We think that’s one of the reasons why our oral approaches can have significant advantages.”

Challenges to developing a norovirus vaccine have included a lack of good animal models to use in research and a lack of an ability to grow the virus well in cell culture, Dr. Tucker said.

Vaxart experienced disruptions in its research during the early stages of the pandemic but has since picked up the pace of its efforts to develop its oral vaccine, Dr. Tucker said during the interview.

In a recent filing with the Securities and Exchange Commission, Vaxart said in early 2021 it resumed its norovirus vaccine program by initiating three clinical studies. These included a phase 1b placebo-controlled dose ranging study in healthy elderly adults aged 55-80. Data from these trials may be unveiled in the coming months.

Vaxart said that this year it has already initiated a phase 2 norovirus challenge study, which will evaluate safety, immunogenicity, and clinical efficacy of a vaccine candidate against placebo.

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

Scientists are trying different approaches to developing vaccines against norovirus, seeking to replicate the success seen in developing shots against rotavirus.

Speaking at the 12th World Congress of the World Society for Pediatric Infectious Diseases (WSPID), Miguel O’Ryan, MD, of the University of Chile, Santiago, presented an overview of candidate vaccines. Dr. O’Ryan has been involved for many years with research on rotavirus vaccines and has branched into work with the somewhat similar norovirus.

With advances in preventing rotavirus, norovirus has emerged in recent years as a leading cause of acute gastroenteritis (AGE) in most countries worldwide. It’s associated with almost 20% of all acute diarrheal cases globally and with an estimated 685 million episodes and 212,000 deaths annually, Dr. O’Ryan and coauthors reported in a review in the journal Viruses.

If successful, norovirus vaccines may be used someday to prevent outbreaks among military personnel, as this contagious virus has the potential to disrupt missions, Dr. O’Ryan and coauthors wrote. They also said people might consider getting norovirus vaccines ahead of trips to prevent traveler’s diarrhea. But most importantly, these kinds of vaccines could reduce diarrhea-associated hospitalizations and deaths of children. 

Takeda Pharmaceutical Company, for whom Dr. O’Ryan has done consulting, last year announced a collaboration with Frazier Healthcare Partners to launch HilleVax. Based in Boston, the company is intended to commercialize Takeda’s norovirus vaccine candidate.

The Takeda-HilleVax candidate vaccine injection has advanced as far as phase 2 studies, including a test done over two winter seasons in U.S. Navy recruits. Takeda and U.S. Navy scientists reported in 2020 in the journal Vaccine that the primary efficacy outcome for this test could not be evaluated due to an unexpectedly low number of cases of norovirus. Still, data taken from this study indicate that the vaccine induces a broad immune response, the scientists reported.

In his WSPID presentation, Dr. O’Ryan also mentioned an oral norovirus vaccine candidate that the company Vaxart is developing, referring to this as a “very interesting approach.” 
 

Betting on the gut

Based in South San Francisco, California, Vaxart is pursuing a theory that a vaccine designed to generate mucosal antibodies locally in the intestine, in addition to systemic antibodies in the blood, may better protect against norovirus infection than an injectable vaccine.

“A key ability to protect against norovirus needs to come from an intestinal immune response, and injected vaccines don’t give those very well,” Sean Tucker, PhD, the founder and chief scientific officer of Vaxart, told this news organization in an interview. “We think that’s one of the reasons why our oral approaches can have significant advantages.”

Challenges to developing a norovirus vaccine have included a lack of good animal models to use in research and a lack of an ability to grow the virus well in cell culture, Dr. Tucker said.

Vaxart experienced disruptions in its research during the early stages of the pandemic but has since picked up the pace of its efforts to develop its oral vaccine, Dr. Tucker said during the interview.

In a recent filing with the Securities and Exchange Commission, Vaxart said in early 2021 it resumed its norovirus vaccine program by initiating three clinical studies. These included a phase 1b placebo-controlled dose ranging study in healthy elderly adults aged 55-80. Data from these trials may be unveiled in the coming months.

Vaxart said that this year it has already initiated a phase 2 norovirus challenge study, which will evaluate safety, immunogenicity, and clinical efficacy of a vaccine candidate against placebo.

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

The World Health Organization is expected to recommend truncating treatment of children with mild tuberculosis by 2 months – from 6 months to 4 – after a randomized trial found similar outcomes with the shorter regimen.

An international team of investigators found the abbreviated course of antibiotics was no less effective or safe than conventional treatment and saved an average of $17.34 per child – money that could be used to mitigate the toll of TB, which is estimated to sicken 1.1 million children worldwide each year.

The findings come as deaths from TB are rising as a result of the COVID-19 pandemic, which has hindered efforts to find and treat patients. In 2020, according to the WHO, an estimated 1.5 million people died from TB, the first year-over-year increase in such deaths since 2005.

Nearly a quarter of children with TB die, primarily because they go undiagnosed, according to the researchers, who published the study in the New England Journal of Medicine. Shorter treatment “translates into very large cost savings that could be used to improve screening and diagnosis to address the current case detection gap,” first author Anna Turkova, MD, of University College London, told this news organization.

The standard TB regimen is based on trials in adults with severe respiratory disease. However, about two-thirds of children have nonsevere infections.

For the study, Dr. Turkova and colleagues assigned 1,204 children with TB in four countries – Uganda, Zambia, South Africa, and India – to either a 4- or 6-month regimen with first-line medications rifampin, isoniazid, pyrazinamide, and ethambutol. Participants were aged 2 months to 15 years and had symptomatic nonsevere lung or lymph node infections with a negative test on a sputum smear microscopy. Eleven percent also had HIV.

After 18 months, 16 participants in the group that received the shortened treatment and 18 in the standard treatment group had experienced an unfavorable outcome – defined as treatment failure, recurrence of TB, loss to follow-up, or death (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5).

Similar numbers – 47 in the 4-month group and 48 in the 6-month group – experienced severe or life-threatening adverse events, most commonly chest infections, such as pneumonia, and liver problems, during treatment or up to 30 days after the last dose.  
 

New guidelines coming soon

The WHO plans to issue new guidelines and a handbook for TB management in children and adolescents on March 24, World Tuberculosis Day, a spokesman for the agency told Medscape.

Anna Mandalakas, MD, PhD, director of the Global Tuberculosis Program at Baylor College of Medicine, department of pediatrics, Houston, said the shorter regimen should enable more children to successfully complete TB treatment.

“It can be challenging to convince young children to take medications on a regular basis for 6 months,” Dr. Mandalakas, a member of a WHO guidelines development group that reviewed the study, told this news organization. “Despite best intentions, parents often become fatigued and give up the medicine battle.”

Leo Martinez, PhD, an epidemiologist at Boston University School of Public Health who studies pediatric TB, noted that study’s cost-effectiveness analysis applies only to health care costs. Families often suffer financially through lost wages, transportation to health care facilities, and lost employment, fueling a cycle of poverty and disease in low-income countries, he said.

A WHO statement noted that long treatment regimens can add toxicity and risk of drug interactions for children with HIV.

Separate efforts have been underway to hasten TB treatment in different groups of patients. A study published in NEJM showed that 4 months of the potent antibiotic rifapentine, along with another antibiotic, moxifloxacin, was non-inferior to the standard 6-month regimen in patients aged 12 and older. According to the editorial accompanying that study, the research illustrated the potential for shorter treatment courses that would be cheaper and less cumbersome, although that particular combination poses hurdles such as adherence issues and potential bacterial resistance.

Experts agreed that improved diagnostic procedures are critical to significantly reducing TB pediatric deaths – an issue that Dr. Turkova said will be addressed in WHO’s forthcoming handbook.

Because no gold-standard test exists for TB, and symptoms often overlap with other infections, widespread screening of children in households where adults have been diagnosed with TB has been found to improve detection of the disease. “Training of health care workers, easy-to-implement diagnostic algorithms, and widely accessible training materials on chest radiography in childhood TB should also improve case finding and treatment initiation,” she said.

The trial was supported by U.K. government and charitable research funders. Dr. Turkova and Dr. Martinez reported no financial disclosures. Dr. Mandalakas reported honoraria from WHO to support the preparation of diagnostics and treatment chapters in the operational handbook, for providing lectures for Medscape, and for serving on a data safety monitoring board for Janssen Pharmaceuticals.

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

The World Health Organization is expected to recommend truncating treatment of children with mild tuberculosis by 2 months – from 6 months to 4 – after a randomized trial found similar outcomes with the shorter regimen.

An international team of investigators found the abbreviated course of antibiotics was no less effective or safe than conventional treatment and saved an average of $17.34 per child – money that could be used to mitigate the toll of TB, which is estimated to sicken 1.1 million children worldwide each year.

The findings come as deaths from TB are rising as a result of the COVID-19 pandemic, which has hindered efforts to find and treat patients. In 2020, according to the WHO, an estimated 1.5 million people died from TB, the first year-over-year increase in such deaths since 2005.

Nearly a quarter of children with TB die, primarily because they go undiagnosed, according to the researchers, who published the study in the New England Journal of Medicine. Shorter treatment “translates into very large cost savings that could be used to improve screening and diagnosis to address the current case detection gap,” first author Anna Turkova, MD, of University College London, told this news organization.

The standard TB regimen is based on trials in adults with severe respiratory disease. However, about two-thirds of children have nonsevere infections.

For the study, Dr. Turkova and colleagues assigned 1,204 children with TB in four countries – Uganda, Zambia, South Africa, and India – to either a 4- or 6-month regimen with first-line medications rifampin, isoniazid, pyrazinamide, and ethambutol. Participants were aged 2 months to 15 years and had symptomatic nonsevere lung or lymph node infections with a negative test on a sputum smear microscopy. Eleven percent also had HIV.

After 18 months, 16 participants in the group that received the shortened treatment and 18 in the standard treatment group had experienced an unfavorable outcome – defined as treatment failure, recurrence of TB, loss to follow-up, or death (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5).

Similar numbers – 47 in the 4-month group and 48 in the 6-month group – experienced severe or life-threatening adverse events, most commonly chest infections, such as pneumonia, and liver problems, during treatment or up to 30 days after the last dose.  
 

New guidelines coming soon

The WHO plans to issue new guidelines and a handbook for TB management in children and adolescents on March 24, World Tuberculosis Day, a spokesman for the agency told Medscape.

Anna Mandalakas, MD, PhD, director of the Global Tuberculosis Program at Baylor College of Medicine, department of pediatrics, Houston, said the shorter regimen should enable more children to successfully complete TB treatment.

“It can be challenging to convince young children to take medications on a regular basis for 6 months,” Dr. Mandalakas, a member of a WHO guidelines development group that reviewed the study, told this news organization. “Despite best intentions, parents often become fatigued and give up the medicine battle.”

Leo Martinez, PhD, an epidemiologist at Boston University School of Public Health who studies pediatric TB, noted that study’s cost-effectiveness analysis applies only to health care costs. Families often suffer financially through lost wages, transportation to health care facilities, and lost employment, fueling a cycle of poverty and disease in low-income countries, he said.

A WHO statement noted that long treatment regimens can add toxicity and risk of drug interactions for children with HIV.

Separate efforts have been underway to hasten TB treatment in different groups of patients. A study published in NEJM showed that 4 months of the potent antibiotic rifapentine, along with another antibiotic, moxifloxacin, was non-inferior to the standard 6-month regimen in patients aged 12 and older. According to the editorial accompanying that study, the research illustrated the potential for shorter treatment courses that would be cheaper and less cumbersome, although that particular combination poses hurdles such as adherence issues and potential bacterial resistance.

Experts agreed that improved diagnostic procedures are critical to significantly reducing TB pediatric deaths – an issue that Dr. Turkova said will be addressed in WHO’s forthcoming handbook.

Because no gold-standard test exists for TB, and symptoms often overlap with other infections, widespread screening of children in households where adults have been diagnosed with TB has been found to improve detection of the disease. “Training of health care workers, easy-to-implement diagnostic algorithms, and widely accessible training materials on chest radiography in childhood TB should also improve case finding and treatment initiation,” she said.

The trial was supported by U.K. government and charitable research funders. Dr. Turkova and Dr. Martinez reported no financial disclosures. Dr. Mandalakas reported honoraria from WHO to support the preparation of diagnostics and treatment chapters in the operational handbook, for providing lectures for Medscape, and for serving on a data safety monitoring board for Janssen Pharmaceuticals.

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

The World Health Organization is expected to recommend truncating treatment of children with mild tuberculosis by 2 months – from 6 months to 4 – after a randomized trial found similar outcomes with the shorter regimen.

An international team of investigators found the abbreviated course of antibiotics was no less effective or safe than conventional treatment and saved an average of $17.34 per child – money that could be used to mitigate the toll of TB, which is estimated to sicken 1.1 million children worldwide each year.

The findings come as deaths from TB are rising as a result of the COVID-19 pandemic, which has hindered efforts to find and treat patients. In 2020, according to the WHO, an estimated 1.5 million people died from TB, the first year-over-year increase in such deaths since 2005.

Nearly a quarter of children with TB die, primarily because they go undiagnosed, according to the researchers, who published the study in the New England Journal of Medicine. Shorter treatment “translates into very large cost savings that could be used to improve screening and diagnosis to address the current case detection gap,” first author Anna Turkova, MD, of University College London, told this news organization.

The standard TB regimen is based on trials in adults with severe respiratory disease. However, about two-thirds of children have nonsevere infections.

For the study, Dr. Turkova and colleagues assigned 1,204 children with TB in four countries – Uganda, Zambia, South Africa, and India – to either a 4- or 6-month regimen with first-line medications rifampin, isoniazid, pyrazinamide, and ethambutol. Participants were aged 2 months to 15 years and had symptomatic nonsevere lung or lymph node infections with a negative test on a sputum smear microscopy. Eleven percent also had HIV.

After 18 months, 16 participants in the group that received the shortened treatment and 18 in the standard treatment group had experienced an unfavorable outcome – defined as treatment failure, recurrence of TB, loss to follow-up, or death (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5).

Similar numbers – 47 in the 4-month group and 48 in the 6-month group – experienced severe or life-threatening adverse events, most commonly chest infections, such as pneumonia, and liver problems, during treatment or up to 30 days after the last dose.  
 

New guidelines coming soon

The WHO plans to issue new guidelines and a handbook for TB management in children and adolescents on March 24, World Tuberculosis Day, a spokesman for the agency told Medscape.

Anna Mandalakas, MD, PhD, director of the Global Tuberculosis Program at Baylor College of Medicine, department of pediatrics, Houston, said the shorter regimen should enable more children to successfully complete TB treatment.

“It can be challenging to convince young children to take medications on a regular basis for 6 months,” Dr. Mandalakas, a member of a WHO guidelines development group that reviewed the study, told this news organization. “Despite best intentions, parents often become fatigued and give up the medicine battle.”

Leo Martinez, PhD, an epidemiologist at Boston University School of Public Health who studies pediatric TB, noted that study’s cost-effectiveness analysis applies only to health care costs. Families often suffer financially through lost wages, transportation to health care facilities, and lost employment, fueling a cycle of poverty and disease in low-income countries, he said.

A WHO statement noted that long treatment regimens can add toxicity and risk of drug interactions for children with HIV.

Separate efforts have been underway to hasten TB treatment in different groups of patients. A study published in NEJM showed that 4 months of the potent antibiotic rifapentine, along with another antibiotic, moxifloxacin, was non-inferior to the standard 6-month regimen in patients aged 12 and older. According to the editorial accompanying that study, the research illustrated the potential for shorter treatment courses that would be cheaper and less cumbersome, although that particular combination poses hurdles such as adherence issues and potential bacterial resistance.

Experts agreed that improved diagnostic procedures are critical to significantly reducing TB pediatric deaths – an issue that Dr. Turkova said will be addressed in WHO’s forthcoming handbook.

Because no gold-standard test exists for TB, and symptoms often overlap with other infections, widespread screening of children in households where adults have been diagnosed with TB has been found to improve detection of the disease. “Training of health care workers, easy-to-implement diagnostic algorithms, and widely accessible training materials on chest radiography in childhood TB should also improve case finding and treatment initiation,” she said.

The trial was supported by U.K. government and charitable research funders. Dr. Turkova and Dr. Martinez reported no financial disclosures. Dr. Mandalakas reported honoraria from WHO to support the preparation of diagnostics and treatment chapters in the operational handbook, for providing lectures for Medscape, and for serving on a data safety monitoring board for Janssen Pharmaceuticals.

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

“People don’t think about schizophrenia when they think about HIV,” Christina Mangurian, MD, professor of clinical psychiatry and vice chair for diversity and health equity at the University of California, San Francisco (UCSF), told this news organization.

University of California, San Francisco

The problem is complicated. According to the Centers for Disease Control and Prevention and National Institutes of Health, roughly 6% of people with serious mental illness are living with HIV, a rate that is about 10 times higher than the general U.S. population (0.4%). However, findings from a study by Dr. Mangurian and her team, published online in the journal AIDS, demonstrated that half of Medicaid patients with schizophrenia and HIV admitted to inpatient units in New York State were not coded as such upon discharge.

These data raise the question: How many people living with comorbid HIV and serious mental illness are diagnosed, virally suppressed, and/or lost to treatment as a result of the stigma associated with both conditions, lack of social support, and under-recognition by practitioners that a problem even exists?
 

Lost in the care continuum

Dr. Mangurian and her research team examined documentation of pre-existing HIV/AIDS diagnoses and absence of ICD-9-CM HIV/AIDS coding at psychiatric discharge among 14,602 adults (aged 18-64 years) admitted to hospital inpatient units in New York State between Jan. 1, 2012, and Dec. 31, 2013. HIV diagnoses were defined as recent (within 30 days of admission) or distant (within 30-366 days of admission), and first admission was used as the index in people with multiple hospitalizations.

People living with HIV comprised 5.1% (741) of the overall dataset; 34% were diagnosed with schizophrenia and 27.9% with bipolar disorders. Overall, 54.5% were male and 50.7% were non-Hispanic Black. Furthermore, 58.3% were discharged without HIV/AIDS ICD-9 coding, reinforcing the likelihood that they were lost in the care continuum.

Dr. Mangurian explained that this break in the chain of care upon discharge can have an important impact on efforts to break the cycle of HIV transmission.

“There’s data that people with serious mental illnesses like schizophrenia are less likely to have sex, but when they do they’re more likely to engage in risky sexual behaviors, including sex for money [and] unprotected sex with partners who use injection drugs or who have HIV,” she said.

Although the majority of patients – both with and without prior HIV diagnoses – were older, adjusted models demonstrated that people aged 18-24 years had more than twice the odds of having their HIV/AIDS undocumented at discharge, compared with older adults aged 55-64 years (adjusted odds ratio, 2.37; P = .038), as were those aged 25-34 years (aOR, 2.17; P = .003). Individuals with more distant HIV diagnoses had three times the odds for an undocumented HIV/AIDS discharge, compared with more recent diagnoses (aOR, 3.25; P < .001). 

Additional factors contributing to the lack of ICD-9 discharge coding included shorter lengths of stay (0-3 days vs. 15-30 days; aOR, 0.03; P = .01) and fewer HIV claims for HIV/AIDS services before hospitalization (1-2 vs. 3-9; aOR, 0.34; P < .01). Hospitals serving medium or high levels of Medicaid patients were also less likely to document HIV/AIDS before discharge (medium aOR, 1.69, P = .01; high aOR, 1.71, P = .03).

The study is not without limitations. For example, the 10-year-old dataset might not entirely reflect more recent structural or systemic changes for improving HIV detection on inpatient psychiatric units. Moreover, there was no comparator group without psychiatric inpatient admission.

Still, “[if these patients] didn’t have a discharge diagnosis, then it’s possible that they were not managed for their HIV, or their HIV was not addressed while they were in the hospital,” Sarah Andrews, MD, assistant professor of psychiatry and behavioral sciences and AIDS psychiatrist at Johns Hopkins School of Medicine, Baltimore, explained.

Johns Hopkins School of Medicine

Severe mental health an HIV disparity

Despite the burden of HIV among patient populations with serious mental health issues and data suggesting that these populations are over-represented among new HIV infections, the study findings point to an important missed opportunity for meeting several key outcomes on the HIV/AIDS care continuum, especially linkage to and retention in care.

The challenge is multifactorial.

In an earlier publication appearing in April 2021 in The Lancet HIV, Dr. Mangurian and colleagues explore a concept known as the “purview paradox,” which refers to a practitioner’s belief about who should be responsible for offering patients a particular intervention.

Structural and systemic issues also abound, as psychiatry records are often kept separate from the rest of the medical system due to insurer billing issues. “The true integration of all psychiatric and medical care has to happen to make sure that all of our patients receive the care that they deserve,” explained Dr. Mangurian.

Dr. Andrews agrees. “HIV care, as well as psychiatry, case management, pharmacy ... putting them together really helps decrease the risk of falling through the cracks and being able to refer appropriately for mental health,” she said.

Aside from changing practitioner attitudes and awareness and changing systems to include the wrap-around care model, current guidelines also need to reflect the role that patients with HIV and psychiatric comorbidities play in HIV transmission. Dr. Andrews and Dr. Mangurian agree: Routine screening in psychiatric inpatient units might be a good start.

The study was independently supported. Dr. Mangurian has reported grant funding from Genentech Charitable Foundation. Dr. Andrews has reported no relevant financial relationships.

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

“People don’t think about schizophrenia when they think about HIV,” Christina Mangurian, MD, professor of clinical psychiatry and vice chair for diversity and health equity at the University of California, San Francisco (UCSF), told this news organization.

University of California, San Francisco

The problem is complicated. According to the Centers for Disease Control and Prevention and National Institutes of Health, roughly 6% of people with serious mental illness are living with HIV, a rate that is about 10 times higher than the general U.S. population (0.4%). However, findings from a study by Dr. Mangurian and her team, published online in the journal AIDS, demonstrated that half of Medicaid patients with schizophrenia and HIV admitted to inpatient units in New York State were not coded as such upon discharge.

These data raise the question: How many people living with comorbid HIV and serious mental illness are diagnosed, virally suppressed, and/or lost to treatment as a result of the stigma associated with both conditions, lack of social support, and under-recognition by practitioners that a problem even exists?
 

Lost in the care continuum

Dr. Mangurian and her research team examined documentation of pre-existing HIV/AIDS diagnoses and absence of ICD-9-CM HIV/AIDS coding at psychiatric discharge among 14,602 adults (aged 18-64 years) admitted to hospital inpatient units in New York State between Jan. 1, 2012, and Dec. 31, 2013. HIV diagnoses were defined as recent (within 30 days of admission) or distant (within 30-366 days of admission), and first admission was used as the index in people with multiple hospitalizations.

People living with HIV comprised 5.1% (741) of the overall dataset; 34% were diagnosed with schizophrenia and 27.9% with bipolar disorders. Overall, 54.5% were male and 50.7% were non-Hispanic Black. Furthermore, 58.3% were discharged without HIV/AIDS ICD-9 coding, reinforcing the likelihood that they were lost in the care continuum.

Dr. Mangurian explained that this break in the chain of care upon discharge can have an important impact on efforts to break the cycle of HIV transmission.

“There’s data that people with serious mental illnesses like schizophrenia are less likely to have sex, but when they do they’re more likely to engage in risky sexual behaviors, including sex for money [and] unprotected sex with partners who use injection drugs or who have HIV,” she said.

Although the majority of patients – both with and without prior HIV diagnoses – were older, adjusted models demonstrated that people aged 18-24 years had more than twice the odds of having their HIV/AIDS undocumented at discharge, compared with older adults aged 55-64 years (adjusted odds ratio, 2.37; P = .038), as were those aged 25-34 years (aOR, 2.17; P = .003). Individuals with more distant HIV diagnoses had three times the odds for an undocumented HIV/AIDS discharge, compared with more recent diagnoses (aOR, 3.25; P < .001). 

Additional factors contributing to the lack of ICD-9 discharge coding included shorter lengths of stay (0-3 days vs. 15-30 days; aOR, 0.03; P = .01) and fewer HIV claims for HIV/AIDS services before hospitalization (1-2 vs. 3-9; aOR, 0.34; P < .01). Hospitals serving medium or high levels of Medicaid patients were also less likely to document HIV/AIDS before discharge (medium aOR, 1.69, P = .01; high aOR, 1.71, P = .03).

The study is not without limitations. For example, the 10-year-old dataset might not entirely reflect more recent structural or systemic changes for improving HIV detection on inpatient psychiatric units. Moreover, there was no comparator group without psychiatric inpatient admission.

Still, “[if these patients] didn’t have a discharge diagnosis, then it’s possible that they were not managed for their HIV, or their HIV was not addressed while they were in the hospital,” Sarah Andrews, MD, assistant professor of psychiatry and behavioral sciences and AIDS psychiatrist at Johns Hopkins School of Medicine, Baltimore, explained.

Johns Hopkins School of Medicine

Severe mental health an HIV disparity

Despite the burden of HIV among patient populations with serious mental health issues and data suggesting that these populations are over-represented among new HIV infections, the study findings point to an important missed opportunity for meeting several key outcomes on the HIV/AIDS care continuum, especially linkage to and retention in care.

The challenge is multifactorial.

In an earlier publication appearing in April 2021 in The Lancet HIV, Dr. Mangurian and colleagues explore a concept known as the “purview paradox,” which refers to a practitioner’s belief about who should be responsible for offering patients a particular intervention.

Structural and systemic issues also abound, as psychiatry records are often kept separate from the rest of the medical system due to insurer billing issues. “The true integration of all psychiatric and medical care has to happen to make sure that all of our patients receive the care that they deserve,” explained Dr. Mangurian.

Dr. Andrews agrees. “HIV care, as well as psychiatry, case management, pharmacy ... putting them together really helps decrease the risk of falling through the cracks and being able to refer appropriately for mental health,” she said.

Aside from changing practitioner attitudes and awareness and changing systems to include the wrap-around care model, current guidelines also need to reflect the role that patients with HIV and psychiatric comorbidities play in HIV transmission. Dr. Andrews and Dr. Mangurian agree: Routine screening in psychiatric inpatient units might be a good start.

The study was independently supported. Dr. Mangurian has reported grant funding from Genentech Charitable Foundation. Dr. Andrews has reported no relevant financial relationships.

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

“People don’t think about schizophrenia when they think about HIV,” Christina Mangurian, MD, professor of clinical psychiatry and vice chair for diversity and health equity at the University of California, San Francisco (UCSF), told this news organization.

University of California, San Francisco

The problem is complicated. According to the Centers for Disease Control and Prevention and National Institutes of Health, roughly 6% of people with serious mental illness are living with HIV, a rate that is about 10 times higher than the general U.S. population (0.4%). However, findings from a study by Dr. Mangurian and her team, published online in the journal AIDS, demonstrated that half of Medicaid patients with schizophrenia and HIV admitted to inpatient units in New York State were not coded as such upon discharge.

These data raise the question: How many people living with comorbid HIV and serious mental illness are diagnosed, virally suppressed, and/or lost to treatment as a result of the stigma associated with both conditions, lack of social support, and under-recognition by practitioners that a problem even exists?
 

Lost in the care continuum

Dr. Mangurian and her research team examined documentation of pre-existing HIV/AIDS diagnoses and absence of ICD-9-CM HIV/AIDS coding at psychiatric discharge among 14,602 adults (aged 18-64 years) admitted to hospital inpatient units in New York State between Jan. 1, 2012, and Dec. 31, 2013. HIV diagnoses were defined as recent (within 30 days of admission) or distant (within 30-366 days of admission), and first admission was used as the index in people with multiple hospitalizations.

People living with HIV comprised 5.1% (741) of the overall dataset; 34% were diagnosed with schizophrenia and 27.9% with bipolar disorders. Overall, 54.5% were male and 50.7% were non-Hispanic Black. Furthermore, 58.3% were discharged without HIV/AIDS ICD-9 coding, reinforcing the likelihood that they were lost in the care continuum.

Dr. Mangurian explained that this break in the chain of care upon discharge can have an important impact on efforts to break the cycle of HIV transmission.

“There’s data that people with serious mental illnesses like schizophrenia are less likely to have sex, but when they do they’re more likely to engage in risky sexual behaviors, including sex for money [and] unprotected sex with partners who use injection drugs or who have HIV,” she said.

Although the majority of patients – both with and without prior HIV diagnoses – were older, adjusted models demonstrated that people aged 18-24 years had more than twice the odds of having their HIV/AIDS undocumented at discharge, compared with older adults aged 55-64 years (adjusted odds ratio, 2.37; P = .038), as were those aged 25-34 years (aOR, 2.17; P = .003). Individuals with more distant HIV diagnoses had three times the odds for an undocumented HIV/AIDS discharge, compared with more recent diagnoses (aOR, 3.25; P < .001). 

Additional factors contributing to the lack of ICD-9 discharge coding included shorter lengths of stay (0-3 days vs. 15-30 days; aOR, 0.03; P = .01) and fewer HIV claims for HIV/AIDS services before hospitalization (1-2 vs. 3-9; aOR, 0.34; P < .01). Hospitals serving medium or high levels of Medicaid patients were also less likely to document HIV/AIDS before discharge (medium aOR, 1.69, P = .01; high aOR, 1.71, P = .03).

The study is not without limitations. For example, the 10-year-old dataset might not entirely reflect more recent structural or systemic changes for improving HIV detection on inpatient psychiatric units. Moreover, there was no comparator group without psychiatric inpatient admission.

Still, “[if these patients] didn’t have a discharge diagnosis, then it’s possible that they were not managed for their HIV, or their HIV was not addressed while they were in the hospital,” Sarah Andrews, MD, assistant professor of psychiatry and behavioral sciences and AIDS psychiatrist at Johns Hopkins School of Medicine, Baltimore, explained.

Johns Hopkins School of Medicine

Severe mental health an HIV disparity

Despite the burden of HIV among patient populations with serious mental health issues and data suggesting that these populations are over-represented among new HIV infections, the study findings point to an important missed opportunity for meeting several key outcomes on the HIV/AIDS care continuum, especially linkage to and retention in care.

The challenge is multifactorial.

In an earlier publication appearing in April 2021 in The Lancet HIV, Dr. Mangurian and colleagues explore a concept known as the “purview paradox,” which refers to a practitioner’s belief about who should be responsible for offering patients a particular intervention.

Structural and systemic issues also abound, as psychiatry records are often kept separate from the rest of the medical system due to insurer billing issues. “The true integration of all psychiatric and medical care has to happen to make sure that all of our patients receive the care that they deserve,” explained Dr. Mangurian.

Dr. Andrews agrees. “HIV care, as well as psychiatry, case management, pharmacy ... putting them together really helps decrease the risk of falling through the cracks and being able to refer appropriately for mental health,” she said.

Aside from changing practitioner attitudes and awareness and changing systems to include the wrap-around care model, current guidelines also need to reflect the role that patients with HIV and psychiatric comorbidities play in HIV transmission. Dr. Andrews and Dr. Mangurian agree: Routine screening in psychiatric inpatient units might be a good start.

The study was independently supported. Dr. Mangurian has reported grant funding from Genentech Charitable Foundation. Dr. Andrews has reported no relevant financial relationships.

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

New cases of COVID-19 in U.S. children have fallen to their lowest level since the beginning of the Delta surge in July of 2021, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Just under 42,000 new cases were reported during the week of March 4-10, making it the 7th consecutive week of declines since the peak of the Omicron surge in January. Over those 7 weeks, new cases dropped over 96% from the 1.15 million reported for Jan. 14-20, based on data collected by the AAP and CHA from state and territorial health departments.

The last time that the weekly count was below 42,000 was July 16-22, 2021, when almost 39,000 cases were reported in the midst of the Delta upsurge. That was shortly after cases had reached their lowest point, 8,447, since the early stages of the pandemic in 2020, the AAP/CHA data show.

The cumulative number of pediatric cases is now up to 12.7 million, while the overall proportion of cases occurring in children held steady at 19.0% for the 4th week in a row, the AAP and CHA said in their weekly COVID-19 report. The Centers for Disease Control and Prevention, using an age range of 0-18 versus the states’ variety of ages, puts total cases at 11.7 million and deaths at 1,656 as of March 14.

Data from the CDC’s COVID-19–Associated Hospitalization Surveillance Network show that hospitalizations with laboratory-confirmed infection were down by 50% in children aged 0-4 years, by 63% among 5- to 11-year-olds, and by 58% in those aged 12-17 years for the week of Feb. 27 to March 5, compared with the week before.

The pace of vaccination continues to follow a similar trend, as the declines seen through February have continued into March. Cumulatively, 33.7% of children aged 5-11 have received at least one dose, and 26.8% are fully vaccinated, with corresponding numbers of 68.0% and 58.0% for children aged 12-17, the CDC reported on its COVID Data Tracker.

State-level data show that children aged 5-11 in Vermont, with a rate of 65%, are the most likely to have received at least one dose of COVID vaccine, while just 15% of 5- to 11-year-olds in Alabama, Louisiana, and Mississippi have gotten their first dose. Among children aged 12-17, that rate ranges from 40% in Wyoming to 94% in Hawaii, Massachusetts, and Rhode Island, the AAP said in a separate report based on CDC data.

In a recent report involving 1,364 children aged 5-15 years, two doses of the COVID-19 vaccine reduced the risk of infection from the Omicron variant by 31% in children aged 5-11 years and by 59% among children aged 12-15 years, said Ashley L. Fowlkes, ScD, of the CDC’s COVID-19 Emergency Response Team, and associates (MMWR 2022 Mar 11;71).
 

New cases of COVID-19 in U.S. children have fallen to their lowest level since the beginning of the Delta surge in July of 2021, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Just under 42,000 new cases were reported during the week of March 4-10, making it the 7th consecutive week of declines since the peak of the Omicron surge in January. Over those 7 weeks, new cases dropped over 96% from the 1.15 million reported for Jan. 14-20, based on data collected by the AAP and CHA from state and territorial health departments.

The last time that the weekly count was below 42,000 was July 16-22, 2021, when almost 39,000 cases were reported in the midst of the Delta upsurge. That was shortly after cases had reached their lowest point, 8,447, since the early stages of the pandemic in 2020, the AAP/CHA data show.

The cumulative number of pediatric cases is now up to 12.7 million, while the overall proportion of cases occurring in children held steady at 19.0% for the 4th week in a row, the AAP and CHA said in their weekly COVID-19 report. The Centers for Disease Control and Prevention, using an age range of 0-18 versus the states’ variety of ages, puts total cases at 11.7 million and deaths at 1,656 as of March 14.

Data from the CDC’s COVID-19–Associated Hospitalization Surveillance Network show that hospitalizations with laboratory-confirmed infection were down by 50% in children aged 0-4 years, by 63% among 5- to 11-year-olds, and by 58% in those aged 12-17 years for the week of Feb. 27 to March 5, compared with the week before.

The pace of vaccination continues to follow a similar trend, as the declines seen through February have continued into March. Cumulatively, 33.7% of children aged 5-11 have received at least one dose, and 26.8% are fully vaccinated, with corresponding numbers of 68.0% and 58.0% for children aged 12-17, the CDC reported on its COVID Data Tracker.

State-level data show that children aged 5-11 in Vermont, with a rate of 65%, are the most likely to have received at least one dose of COVID vaccine, while just 15% of 5- to 11-year-olds in Alabama, Louisiana, and Mississippi have gotten their first dose. Among children aged 12-17, that rate ranges from 40% in Wyoming to 94% in Hawaii, Massachusetts, and Rhode Island, the AAP said in a separate report based on CDC data.

In a recent report involving 1,364 children aged 5-15 years, two doses of the COVID-19 vaccine reduced the risk of infection from the Omicron variant by 31% in children aged 5-11 years and by 59% among children aged 12-15 years, said Ashley L. Fowlkes, ScD, of the CDC’s COVID-19 Emergency Response Team, and associates (MMWR 2022 Mar 11;71).
 

New cases of COVID-19 in U.S. children have fallen to their lowest level since the beginning of the Delta surge in July of 2021, according to the American Academy of Pediatrics and the Children’s Hospital Association.

Just under 42,000 new cases were reported during the week of March 4-10, making it the 7th consecutive week of declines since the peak of the Omicron surge in January. Over those 7 weeks, new cases dropped over 96% from the 1.15 million reported for Jan. 14-20, based on data collected by the AAP and CHA from state and territorial health departments.

The last time that the weekly count was below 42,000 was July 16-22, 2021, when almost 39,000 cases were reported in the midst of the Delta upsurge. That was shortly after cases had reached their lowest point, 8,447, since the early stages of the pandemic in 2020, the AAP/CHA data show.

The cumulative number of pediatric cases is now up to 12.7 million, while the overall proportion of cases occurring in children held steady at 19.0% for the 4th week in a row, the AAP and CHA said in their weekly COVID-19 report. The Centers for Disease Control and Prevention, using an age range of 0-18 versus the states’ variety of ages, puts total cases at 11.7 million and deaths at 1,656 as of March 14.

Data from the CDC’s COVID-19–Associated Hospitalization Surveillance Network show that hospitalizations with laboratory-confirmed infection were down by 50% in children aged 0-4 years, by 63% among 5- to 11-year-olds, and by 58% in those aged 12-17 years for the week of Feb. 27 to March 5, compared with the week before.

The pace of vaccination continues to follow a similar trend, as the declines seen through February have continued into March. Cumulatively, 33.7% of children aged 5-11 have received at least one dose, and 26.8% are fully vaccinated, with corresponding numbers of 68.0% and 58.0% for children aged 12-17, the CDC reported on its COVID Data Tracker.

State-level data show that children aged 5-11 in Vermont, with a rate of 65%, are the most likely to have received at least one dose of COVID vaccine, while just 15% of 5- to 11-year-olds in Alabama, Louisiana, and Mississippi have gotten their first dose. Among children aged 12-17, that rate ranges from 40% in Wyoming to 94% in Hawaii, Massachusetts, and Rhode Island, the AAP said in a separate report based on CDC data.

In a recent report involving 1,364 children aged 5-15 years, two doses of the COVID-19 vaccine reduced the risk of infection from the Omicron variant by 31% in children aged 5-11 years and by 59% among children aged 12-15 years, said Ashley L. Fowlkes, ScD, of the CDC’s COVID-19 Emergency Response Team, and associates (MMWR 2022 Mar 11;71).
 

Heterosexuals with HIV have lower CD4 counts at diagnosis than their gay and bisexual male peers, according to an analysis of more than 300,000 people living with HIV globally.

“It was quite a startling finding for us, because it’s now telling everybody, ‘Look, if you have MSM [men who have sex with men] coming into your clinic, expect CD4 counts at diagnosis to be higher than if the person got the infection as a heterosexual,’” Narendra Dixit, PhD, senior fellow at the Indian Institute of Science’s Centre for Biosystems Science and Engineering, Bangalore, India, said in an interview.

And that means, he said, that the pattern may appear in local clinics.

“If they find that there are differences in the CD4 counts between heterosexuals and MSMs, they should not be surprised anymore,” he said.

Dr. Dixit proposed that the reason for this may be that the viruses transmitted among heterosexuals are more virulent, but the study didn’t provide evidence of that.
 

Immune health at HIV diagnosis

In this study, which was published online March 10 in PLOS Pathogens, Dr. Dixit and colleague Anathu James, PhD, a data scientist and an epidemiologist at the Indian Institute of Science, culled data from 337,119 people captured in studies in the United Kingdom, the United States, Europe, Australia, and China. For all participants, CD4 counts were drawn at the time of diagnosis and before starting HIV treatment. Dr. Dixit and Dr. James then divided the studies by HIV transmission group – gay and bisexual men versus heterosexuals – and then averaged CD4 counts in each study.

Then they created a mathematical model to estimate how quickly each group might progress to an AIDS-defining illness, given those initial CD4 counts.

What they found was that the mean CD4 count was consistently higher in the gay and bisexual males than in the heterosexuals, no matter where they lived. For instance, mean CD4 counts at diagnosis were a mean of 437 cells/mm³ among gay and bisexual men in one European cohort, compared to a mean of 307 among heterosexuals. In the U.S. data, the mean CD4 count for gay and bisexual men was 390, compared to 314 among heterosexuals. In China, the same held true: Gay men had a mean CD4 count of 368 cells/mm³; heterosexuals had a mean CD4 count of 270.

This remained true when they only looked at people between the ages of 13 and 29 years in the United States or whether they were younger than 40 in Europe and Australia. In Europe and Australia, though, heterosexual women younger than 40 had higher CD4 counts than either straight or gay men. But this difference did not reach statistical significance, and gay men had higher CD4 counts overall when the investigators didn’t segregate the data by age group.

“We were stunned,” Dr. Dixit told this news organization. “People never thought there could be a difference in the CD4 counts just because the mode of transmission is different – or, in this case, because the risk groups are different.”

There was no difference, though, in viral load at diagnosis.

In their mathematical model on progression to AIDS, the investigators estimated that these lower CD4 counts at diagnosis would lead to a progression to AIDS that was 19% higher for straight people than for gay and bisexual men. What this implies for practice is less clear. Right now, Dr. Dixit hopes the data will be used to conduct molecular analysis of HIV strains in heterosexuals and gay and bisexual men to see if the HIV circulating in straight communities is different – and perhaps more virulent – than the HIV circulating among gay and bisexual men. Previous research has suggested that CD4 counts can be used as a proxy for virulence.

Dr. Dixit’s mathematical model follows recent news of a highly virulent strain of HIV that’s been present in the Netherlands for decades. “More virulent” in that case meant that it was more highly transmissible and led to higher viral loads and a quicker decline of the immune CD4 cells. So when news of Dr. Dixit’s study went out, it was accompanied by a press release stating as fact that “HIV-1 infections are more virulent when transmitted through penile-vaginal intercourse.” The study’s title states that HIV is “more virulent” in heterosexuals.

But this study doesn’t actually show that, said virology researcher Timothy Henrich, MD, associate professor of medicine at the University of California, San Francisco, in an interview. In the Netherlands study, investigators took the additional step of analyzing HIV genomes. But this was not done in the recent PLOS Pathogens study.

“This was essentially a large meta-analysis of multiple large cohorts across many different countries,” said Dr. Henrich, who was not involved in the study. “There was no in-depth sequence analysis to say, ‘Oh yeah, this is because of a difference in the viruses that are being transmitted.’ If I were reviewing this paper, I probably would have said, ‘This is an interesting observation, but please don’t go overboard in your conclusions.’”

The study made Dr. Henrich want to know more. For instance, what method did each study use to determine CD4 counts? Did they control for the length of time since acquisition? Dr. Henrich said that if they didn’t differentiate between acute infection and chronic infection, he wasn’t sure what conclusions could be drawn from the data. Dr. Dixit told this news organization that they used the plateau level – the point after acute infection when CD4 counts settle into a consistent level. But it’s unclear how far from HIV acquisition each of the people in these studies was.

What Dr. Henrich does know, he said, is that big data are going to continue to change how we think about and investigate HIV transmission and virulence and what it could mean for clinical practice. The National Institutes of Health, for instance, will soon require all researchers receiving their funding to make their raw data publicly available soon after publication.

“We’re going to see a lot more of these large studies going forward,” he said. And if molecular analyses bear out Dr. Dixit’s conclusion – which he called “a big if” – “maybe we could use this study as a way” to do this work in the future.

The study was funded by DBT Network and the Wellcome Trust India Alliance Senior Fellowship. Dr. Dixit has disclosed no relevant financial relationships. Dr. Henrich is conducting studies funded in whole or in part by Merck and Gilead Sciences.

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

Heterosexuals with HIV have lower CD4 counts at diagnosis than their gay and bisexual male peers, according to an analysis of more than 300,000 people living with HIV globally.

“It was quite a startling finding for us, because it’s now telling everybody, ‘Look, if you have MSM [men who have sex with men] coming into your clinic, expect CD4 counts at diagnosis to be higher than if the person got the infection as a heterosexual,’” Narendra Dixit, PhD, senior fellow at the Indian Institute of Science’s Centre for Biosystems Science and Engineering, Bangalore, India, said in an interview.

And that means, he said, that the pattern may appear in local clinics.

“If they find that there are differences in the CD4 counts between heterosexuals and MSMs, they should not be surprised anymore,” he said.

Dr. Dixit proposed that the reason for this may be that the viruses transmitted among heterosexuals are more virulent, but the study didn’t provide evidence of that.
 

Immune health at HIV diagnosis

In this study, which was published online March 10 in PLOS Pathogens, Dr. Dixit and colleague Anathu James, PhD, a data scientist and an epidemiologist at the Indian Institute of Science, culled data from 337,119 people captured in studies in the United Kingdom, the United States, Europe, Australia, and China. For all participants, CD4 counts were drawn at the time of diagnosis and before starting HIV treatment. Dr. Dixit and Dr. James then divided the studies by HIV transmission group – gay and bisexual men versus heterosexuals – and then averaged CD4 counts in each study.

Then they created a mathematical model to estimate how quickly each group might progress to an AIDS-defining illness, given those initial CD4 counts.

What they found was that the mean CD4 count was consistently higher in the gay and bisexual males than in the heterosexuals, no matter where they lived. For instance, mean CD4 counts at diagnosis were a mean of 437 cells/mm³ among gay and bisexual men in one European cohort, compared to a mean of 307 among heterosexuals. In the U.S. data, the mean CD4 count for gay and bisexual men was 390, compared to 314 among heterosexuals. In China, the same held true: Gay men had a mean CD4 count of 368 cells/mm³; heterosexuals had a mean CD4 count of 270.

This remained true when they only looked at people between the ages of 13 and 29 years in the United States or whether they were younger than 40 in Europe and Australia. In Europe and Australia, though, heterosexual women younger than 40 had higher CD4 counts than either straight or gay men. But this difference did not reach statistical significance, and gay men had higher CD4 counts overall when the investigators didn’t segregate the data by age group.

“We were stunned,” Dr. Dixit told this news organization. “People never thought there could be a difference in the CD4 counts just because the mode of transmission is different – or, in this case, because the risk groups are different.”

There was no difference, though, in viral load at diagnosis.

In their mathematical model on progression to AIDS, the investigators estimated that these lower CD4 counts at diagnosis would lead to a progression to AIDS that was 19% higher for straight people than for gay and bisexual men. What this implies for practice is less clear. Right now, Dr. Dixit hopes the data will be used to conduct molecular analysis of HIV strains in heterosexuals and gay and bisexual men to see if the HIV circulating in straight communities is different – and perhaps more virulent – than the HIV circulating among gay and bisexual men. Previous research has suggested that CD4 counts can be used as a proxy for virulence.

Dr. Dixit’s mathematical model follows recent news of a highly virulent strain of HIV that’s been present in the Netherlands for decades. “More virulent” in that case meant that it was more highly transmissible and led to higher viral loads and a quicker decline of the immune CD4 cells. So when news of Dr. Dixit’s study went out, it was accompanied by a press release stating as fact that “HIV-1 infections are more virulent when transmitted through penile-vaginal intercourse.” The study’s title states that HIV is “more virulent” in heterosexuals.

But this study doesn’t actually show that, said virology researcher Timothy Henrich, MD, associate professor of medicine at the University of California, San Francisco, in an interview. In the Netherlands study, investigators took the additional step of analyzing HIV genomes. But this was not done in the recent PLOS Pathogens study.

“This was essentially a large meta-analysis of multiple large cohorts across many different countries,” said Dr. Henrich, who was not involved in the study. “There was no in-depth sequence analysis to say, ‘Oh yeah, this is because of a difference in the viruses that are being transmitted.’ If I were reviewing this paper, I probably would have said, ‘This is an interesting observation, but please don’t go overboard in your conclusions.’”

The study made Dr. Henrich want to know more. For instance, what method did each study use to determine CD4 counts? Did they control for the length of time since acquisition? Dr. Henrich said that if they didn’t differentiate between acute infection and chronic infection, he wasn’t sure what conclusions could be drawn from the data. Dr. Dixit told this news organization that they used the plateau level – the point after acute infection when CD4 counts settle into a consistent level. But it’s unclear how far from HIV acquisition each of the people in these studies was.

What Dr. Henrich does know, he said, is that big data are going to continue to change how we think about and investigate HIV transmission and virulence and what it could mean for clinical practice. The National Institutes of Health, for instance, will soon require all researchers receiving their funding to make their raw data publicly available soon after publication.

“We’re going to see a lot more of these large studies going forward,” he said. And if molecular analyses bear out Dr. Dixit’s conclusion – which he called “a big if” – “maybe we could use this study as a way” to do this work in the future.

The study was funded by DBT Network and the Wellcome Trust India Alliance Senior Fellowship. Dr. Dixit has disclosed no relevant financial relationships. Dr. Henrich is conducting studies funded in whole or in part by Merck and Gilead Sciences.

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

Heterosexuals with HIV have lower CD4 counts at diagnosis than their gay and bisexual male peers, according to an analysis of more than 300,000 people living with HIV globally.

“It was quite a startling finding for us, because it’s now telling everybody, ‘Look, if you have MSM [men who have sex with men] coming into your clinic, expect CD4 counts at diagnosis to be higher than if the person got the infection as a heterosexual,’” Narendra Dixit, PhD, senior fellow at the Indian Institute of Science’s Centre for Biosystems Science and Engineering, Bangalore, India, said in an interview.

And that means, he said, that the pattern may appear in local clinics.

“If they find that there are differences in the CD4 counts between heterosexuals and MSMs, they should not be surprised anymore,” he said.

Dr. Dixit proposed that the reason for this may be that the viruses transmitted among heterosexuals are more virulent, but the study didn’t provide evidence of that.
 

Immune health at HIV diagnosis

In this study, which was published online March 10 in PLOS Pathogens, Dr. Dixit and colleague Anathu James, PhD, a data scientist and an epidemiologist at the Indian Institute of Science, culled data from 337,119 people captured in studies in the United Kingdom, the United States, Europe, Australia, and China. For all participants, CD4 counts were drawn at the time of diagnosis and before starting HIV treatment. Dr. Dixit and Dr. James then divided the studies by HIV transmission group – gay and bisexual men versus heterosexuals – and then averaged CD4 counts in each study.

Then they created a mathematical model to estimate how quickly each group might progress to an AIDS-defining illness, given those initial CD4 counts.

What they found was that the mean CD4 count was consistently higher in the gay and bisexual males than in the heterosexuals, no matter where they lived. For instance, mean CD4 counts at diagnosis were a mean of 437 cells/mm³ among gay and bisexual men in one European cohort, compared to a mean of 307 among heterosexuals. In the U.S. data, the mean CD4 count for gay and bisexual men was 390, compared to 314 among heterosexuals. In China, the same held true: Gay men had a mean CD4 count of 368 cells/mm³; heterosexuals had a mean CD4 count of 270.

This remained true when they only looked at people between the ages of 13 and 29 years in the United States or whether they were younger than 40 in Europe and Australia. In Europe and Australia, though, heterosexual women younger than 40 had higher CD4 counts than either straight or gay men. But this difference did not reach statistical significance, and gay men had higher CD4 counts overall when the investigators didn’t segregate the data by age group.

“We were stunned,” Dr. Dixit told this news organization. “People never thought there could be a difference in the CD4 counts just because the mode of transmission is different – or, in this case, because the risk groups are different.”

There was no difference, though, in viral load at diagnosis.

In their mathematical model on progression to AIDS, the investigators estimated that these lower CD4 counts at diagnosis would lead to a progression to AIDS that was 19% higher for straight people than for gay and bisexual men. What this implies for practice is less clear. Right now, Dr. Dixit hopes the data will be used to conduct molecular analysis of HIV strains in heterosexuals and gay and bisexual men to see if the HIV circulating in straight communities is different – and perhaps more virulent – than the HIV circulating among gay and bisexual men. Previous research has suggested that CD4 counts can be used as a proxy for virulence.

Dr. Dixit’s mathematical model follows recent news of a highly virulent strain of HIV that’s been present in the Netherlands for decades. “More virulent” in that case meant that it was more highly transmissible and led to higher viral loads and a quicker decline of the immune CD4 cells. So when news of Dr. Dixit’s study went out, it was accompanied by a press release stating as fact that “HIV-1 infections are more virulent when transmitted through penile-vaginal intercourse.” The study’s title states that HIV is “more virulent” in heterosexuals.

But this study doesn’t actually show that, said virology researcher Timothy Henrich, MD, associate professor of medicine at the University of California, San Francisco, in an interview. In the Netherlands study, investigators took the additional step of analyzing HIV genomes. But this was not done in the recent PLOS Pathogens study.

“This was essentially a large meta-analysis of multiple large cohorts across many different countries,” said Dr. Henrich, who was not involved in the study. “There was no in-depth sequence analysis to say, ‘Oh yeah, this is because of a difference in the viruses that are being transmitted.’ If I were reviewing this paper, I probably would have said, ‘This is an interesting observation, but please don’t go overboard in your conclusions.’”

The study made Dr. Henrich want to know more. For instance, what method did each study use to determine CD4 counts? Did they control for the length of time since acquisition? Dr. Henrich said that if they didn’t differentiate between acute infection and chronic infection, he wasn’t sure what conclusions could be drawn from the data. Dr. Dixit told this news organization that they used the plateau level – the point after acute infection when CD4 counts settle into a consistent level. But it’s unclear how far from HIV acquisition each of the people in these studies was.

What Dr. Henrich does know, he said, is that big data are going to continue to change how we think about and investigate HIV transmission and virulence and what it could mean for clinical practice. The National Institutes of Health, for instance, will soon require all researchers receiving their funding to make their raw data publicly available soon after publication.

“We’re going to see a lot more of these large studies going forward,” he said. And if molecular analyses bear out Dr. Dixit’s conclusion – which he called “a big if” – “maybe we could use this study as a way” to do this work in the future.

The study was funded by DBT Network and the Wellcome Trust India Alliance Senior Fellowship. Dr. Dixit has disclosed no relevant financial relationships. Dr. Henrich is conducting studies funded in whole or in part by Merck and Gilead Sciences.

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