Health Policy

From the Department of Emergency Medicine, Santa Croce e Carle Hospital, Cuneo, Italy (Drs. Abram, Tosello, Emanuele Bernardi, Allione, Cavalot, Dutto, Corsini, Martini, Sciolla, Sara Bernardi, and Lauria). From the School of Emergency Medicine, University of Turin, Turin, Italy (Drs. Paglietta and Giamello).

Objective: This retrospective and prospective cohort study was designed to describe the characteristics, treatments, and outcomes of patients with SARS-CoV-2 infection (COVID-19) admitted to subintensive care units (SICU) and to identify the variables associated with outcomes. SICUs have been extremely stressed during the pandemic, but most data regarding critically ill COVID-19 patients come from intensive care units (ICUs). Studies about COVID-19 patients in SICUs are lacking.

Setting and participants: The study included 88 COVID-19 patients admitted to our SICU in Cuneo, Italy, between March and May 2020.

Measurements: Clinical and ventilatory data were collected, and patients were divided by outcome. Multivariable logistic regression analysis examined the variables associated with negative outcomes (transfer to the ICU, palliation, or death in a SICU).

Results: A total of 60 patients (68%) had a positive outcome, and 28 patients (32%) had a negative outcome; 69 patients (78%) underwent continuous positive airway pressure (CPAP). Pronation (n = 37 [42%]) had been more frequently adopted in patients who had a positive outcome vs a negative outcome (n = 30 [50%] vs n = 7 [25%]; P = .048), and the median (interquartile range) Pao₂/Fio₂ ratio after 6 hours of prone positioning was lower in patients who had a negative outcome vs a positive outcome (144 [140-168] vs 249 [195-268], P = .006). Independent predictors of a negative outcome were diabetes (odds ratio [OR], 8.22; 95% CI, 1.50-44.70; P = .015), higher D-dimer (OR, 1.28; 95% CI, 1.04-1.57; P = .019), higher lactate dehydrogenase level (OR, 1.003; 95% CI, 1.000-1.006; P = .039), and lower lymphocytes count (OR, 0.996; 95% CI, 0.993-0.999; P = .004).

Conclusion: SICUs have a fundamental role in the treatment of critically ill patients with COVID-19, who require long-term CPAP and pronation cycles. Diabetes, lymphopenia, and high D-dimer and LDH levels are associated with negative outcomes.

Keywords: emergency medicine, noninvasive ventilation, prone position, continuous positive airway pressure.

The COVID-19 pandemic has led to large increases in hospital admissions. Subintensive care units (SICUs) are among the wards most under pressure worldwide,¹ dealing with the increased number of critically ill patients who need noninvasive ventilation, as well as serving as the best alternative to overfilled intensive care units (ICUs). In Italy, SICUs are playing a fundamental role in the management of COVID-19 patients, providing early treatment of respiratory failure by continuous noninvasive ventilation in order to reduce the need for intubation.^2-5 Nevertheless, the great majority of available data about critically ill COVID-19 patients comes from ICUs. Full studies about outcomes of patients in SICUs are lacking and need to be conducted.

We sought to evaluate the characteristics and outcomes of patients admitted to our SICU for COVID-19 to describe the treatments they needed and their impact on prognosis, and to identify the variables associated with patient outcomes.

Methods

Study Design

This cohort study used data from patients who were admitted in the very first weeks of the pandemic. Data were collected retrospectively as well as prospectively, since the ethical committee approved our project. The quality and quantity of data in the 2 groups were comparable.

Data were collected from electronic and written medical records gathered during the patient’s entire stay in our SICU. Data were entered in a database with limited and controlled access. This study complied with the Declaration of Helsinki and was approved by the local ethics committees (ID: MEDURG10).

Study Population

We studied 88 consecutive patients admitted to the SICU of the Santa Croce e Carle Teaching Hospital, Cuneo, Italy, for COVID-19, from March 8 to May 1, 2020. The diagnosis was based on acute respiratory failure associated with SARS-CoV-2 RNA detection on nasopharyngeal swab or tracheal aspirate and/or typical COVID-19 features on a pulmonary computed tomography (CT) scan.⁶ Exclusion criteria were age younger than 18 years and patient denial of permission to use their data for research purposes (the great majority of patients could actively give consent; for patients who were too sick to do so, family members were asked whether they were aware of any reason why the patient would deny consent).

 

 

Clinical Data

The past medical history and recent symptoms description were obtained by manually reviewing medical records. Epidemiological exposure was defined as contact with SARS-CoV-2–positive people or staying in an epidemic outbreak area. Initial vital parameters, venous blood tests, arterial blood gas analysis, chest x-ray, as well as the result of the nasopharyngeal swab were gathered from the emergency department (ED) examination. (Additional swabs could be requested when the first one was negative but clinical suspicion for COVID-19 was high.) Upon admission to the SICU, a standardized panel of blood tests was performed, which was repeated the next day and then every 48 hours. Arterial blood gas analysis was performed when clinically indicated, at least twice a day, or following a scheduled time in patients undergoing pronation. Charlson Comorbidity Index⁷ and MuLBSTA score⁸ were calculated based on the collected data.

Imaging

Chest ultrasonography was performed in the ED at the time of hospitalization and once a day in the SICU. Pulmonary high-resolution computed tomography (HRCT) was performed when clinically indicated or when the results of nasopharyngeal swabs and/or x-ray results were discordant with COVID-19 clinical suspicion. Contrast CT was performed when pulmonary embolism was suspected.

Medical Therapy

Hydroxychloroquine, antiviral agents, tocilizumab, and ruxolitinib were used in the early phase of the pandemic, then were dismissed after evidence of no efficacy.^9-11 Steroids and low-molecular-weight heparin were used afterward. Enoxaparin was used at the standard prophylactic dosage, and 70% of the anticoagulant dosage was also adopted in patients with moderate-to-severe COVID-19 and D-dimer values >3 times the normal value.^12-14 Antibiotics were given when a bacterial superinfection was suspected.

Oxygen and Ventilatory Therapy

Oxygen support or noninvasive ventilation were started based on patients’ respiratory efficacy, estimated by respiratory rate and the ratio of partial pressure of arterial oxygen and fraction of inspired oxygen (P/F ratio).^15,16 Oxygen support was delivered through nasal cannula, Venturi mask, or reservoir mask. Noninvasive ventilation was performed by continuous positive airway pressure (CPAP) when the P/F ratio was <250 or the respiratory rate was >25 breaths per minute, using the helmet interface.^5,17 Prone positioning during CPAP^18-20 was adopted in patients meeting the acute respiratory distress syndrome (ARDS) criteria²¹ and having persistence of respiratory distress and P/F <300 after a 1-hour trial of CPAP.

The prone position was maintained based on patient tolerance. P/F ratio was measured before pronation (T0), after 1 hour of prone position (T1), before resupination (T2), and 6 hours after resupination (T3). With the same timing, the patient was asked to rate their comfort in each position, from 0 (lack of comfort) to 10 (optimal comfort). Delta P/F was defined as the difference between P/F at T3 and basal P/F at T0.

Outcomes

Positive outcomes were defined as patient discharge from the SICU or transfer to a lower-intensity care ward for treatment continuation. Negative outcomes were defined as need for transfer to the ICU, transfer to another ward for palliation, or death in the SICU.

Statistical Analysis

Continuous data are reported as median and interquartile range (IQR); normal distribution of variables was tested using the Shapiro-Wilk test. Categorical variables were reported as absolute number and percentage. The Mann-Whitney test was used to compare continuous variables between groups, and chi-square test with continuity correction was used for categorical variables. The variables that were most significantly associated with a negative outcome on the univariate analysis were included in a stepwise logistic regression analysis, in order to identify independent predictors of patient outcome. Statistical analysis was performed using JASP (JASP Team) software.

 

 

Results

Study Population

Of the 88 patients included in the study, 70% were male; the median age was 66 years (IQR, 60-77). In most patients, the diagnosis of COVID-19 was derived from a positive SARS-CoV-2 nasopharyngeal swab. Six patients, however, maintained a negative swab at all determinations but had clinical and imaging features strongly suggesting COVID-19. No patients met the exclusion criteria. Most patients came from the ED (n = 58 [66%]) or general wards (n = 22 [25%]), while few were transferred from the ICU (n = 8 [9%]). The median length of stay in the SICU was 4 days (IQR, 2-7). An epidemiological link to affected persons or a known virus exposure was identifiable in 37 patients (42%).

Clinical, Laboratory, and Imaging Data

The clinical and anthropometric characteristics of patients are shown in Table 1. Hypertension and smoking habits were prevalent in our population, and the median Charlson Comorbidity Index was 3. Most patients experienced fever, dyspnea, and cough during the days before hospitalization.

Laboratory data showed a marked inflammatory milieu in all studied patients, both at baseline and after 24 and 72 hours. Lymphopenia was observed, along with a significant increase of lactate dehydrogenase (LDH), C-reactive protein (CPR), and D-dimer, and a mild increase of procalcitonin. N-terminal pro-brain natriuretic peptide (NT-proBNP) values were also increased, with normal troponin I values (Table 2).

Medical Therapy

Most patients (89%) received hydroxychloroquine, whereas steroids were used in one-third of the population (36%). Immunomodulators (tocilizumab and ruxolitinib) were restricted to 12 patients (14%). Empirical antiviral therapy was introduced in the first 41 patients (47%). Enoxaparin was the default agent for thromboembolism prophylaxis, and 6 patients (7%) received 70% of the anticoagulating dose.

Oxygen and Ventilatory Therapy

Basal median P/F ratio was 253 (IQR, 218-291), and respiratory rate at triage was 20 breaths/min (IQR, 16-28), underlining a moderate-to-severe respiratory insufficiency at presentation. A total of 69 patients (78%) underwent CPAP, with a median positive end-expiratory pressure (PEEP) of 10.0 cm H₂O (IQR, 7.5-10.0) and fraction of inspired oxygen (Fio₂) of 0.40 (IQR, 0.40-0.50). In 37 patients (42%) who received ongoing CPAP, prone positioning was adopted. In this subgroup, respiratory rate was not significantly different from baseline to resupination (24 vs 25 breaths/min). The median P/F improved from 197 (IQR, 154-236) at baseline to 217 (IQR, 180-262) after pronation (the duration of the prone position was variable, depending on patients’ tolerance: 1 to 6 hours or every pronation cycle). The median delta P/F ratio was 39.4 (IQR, –17.0 to 78.0).

Outcomes

A total of 28 patients (32%) had a negative outcome in the SICU: 8 patients (9%) died, having no clinical indication for higher-intensity care; 6 patients (7%) were transferred to general wards for palliation; and 14 patients (16%) needed an upgrade of cure intensity and were transferred to the ICU. Of these 14 patients, 9 died in the ICU. The total in-hospital mortality of COVID-19 patients, including patients transferred from the SICU to general wards in fair condition, was 27% (n = 24). Clinical, laboratory, and therapeutic characteristics between the 2 groups are shown in Table 4.

Patients who had a negative outcome were significantly older and had more comorbidities, as suggested by a significantly higher prevalence of diabetes and higher Charlson Comorbidity scores (reflecting the mortality risk based on age and comorbidities). The median MuLBSTA score, which estimates the 90-day mortality risk from viral pneumonia, was also higher in patients who had a negative outcome (9.33%). Symptom occurrence was not different in patients with a negative outcome (apart from cough, which was less frequent), but these patients underwent hospitalization earlier—since the appearance of their first COVID-19 symptoms—compared to patients who had a positive outcome. No difference was found in antihypertensive therapy with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers among outcome groups.

More pronounced laboratory abnormalities were found in patients who had a negative outcome, compared to patients who had a positive outcome: lower lymphocytes and higher C-reactive protein (CRP), procalcitonin, D-dimer, LDH, and NT-proBNP. We found no differences in the radiological distribution of pulmonary involvement in patients who had negative or positive outcomes, nor in the adopted medical treatment.

Data showed no difference in CPAP implementation in the 2 groups. However, prone positioning had been more frequently adopted in the group of patients who had a positive outcome, compared with patients who had a negative outcome. No differences of basal P/F were found in patients who had a negative or positive outcome, but the median P/F after 6 hours of prone position was significantly lower in patients who had a negative outcome. The delta P/F ratio did not differ in the 2 groups of patients.

Multivariate Analysis

A logistic regression model was created, including the variables significantly associated with outcomes in the univariate analysis (age, sex, history of diabetes, lymphocytes, CRP, procalcitonin, LDH, NT-proBNP, and D-dimer). In the multivariate analysis, independent predictors of a negative outcome were history of diabetes (odds ratio [OR], 8.22; 95% CI, 1.50-44.70; P =.015), high D-dimer values (OR, 1.28; CI, 1.04-1.57; P = .019), high LDH values (OR, 1.003; CI, 1.000-1.006; P = .039), and low lymphocytes count (OR, 0.996; CI, 0.993-0.999; P = .004).

Discussion

Role of Subintensive Units and Mortality

The novelty of our report is its attempt to investigate the specific group of COVID-19 patients admitted to a SICU. In Italy, SICUs receive acutely ill, spontaneously breathing patients who need (invasive) hemodynamic monitoring, vasoactive medication, renal replacement therapy, chest- tube placement, thrombolysis, and respiratory noninvasive support. The nurse-to-patient ratio is higher than for general wards (usually 1 nurse to every 4 or 5 patients), though lower than for ICUs. In northern Italy, a great number of COVID-19 patients have required this kind of high-intensity care during the pandemic: Noninvasive ventilation support had to be maintained for several days, pronation maneuvers required a high number of people 2 or 3 times a day, and strict monitoring had to be assured. The SICU setting allows patients to buy time as a bridge to progressive reduction of pulmonary involvement, sometimes preventing the need for intubation.

The high prevalence of negative outcomes in the SICU underlines the complexity of COVID-19 patients in this setting. In fact, published data about mortality for patients with severe COVID-19 pneumonia are similar to ours.^22,23

Clinical, Laboratory, and Imaging Data

Our analysis confirmed a high rate of comorbidities in COVID-19 patients²⁴ and their prognostic role with age.^25,26 A marked inflammatory milieu was a negative prognostic indicator, and associated concomitant bacterial superinfection could have led to a worse prognosis (procalcitonin was associated with negative outcomes).²⁷ The cardiovascular system was nevertheless stressed, as suggested by higher values of NT-proBNP in patients with negative outcomes, which could reflect sepsis-related systemic involvement.²⁸

It is known that the pulmonary damage caused by SARS-CoV-2 has a dynamic radiological and clinical course, with early areas of subsegmental consolidation, and bilateral ground-glass opacities predominating later in the course of the disease.²⁹ This could explain why in our population we found no specific radiological pattern leading to a worse outcome.

Medical Therapy

No specific pharmacological therapy was found to be associated with a positive outcome in our study, just like antiviral and immunomodulator therapies failed to demonstrate effectiveness in subsequent pandemic surges. The low statistical power of our study did not allow us to give insight into the effectiveness of steroids and heparin at any dosage.

PEEP Support and Prone Positioning

Continuous positive airway pressure was initiated in the majority of patients and maintained for several days. This was an absolute novelty, because we rarely had to keep patients in helmets for long. This was feasible thanks to the SICU’s high nurse-to-patient ratio and the possibility of providing monitored sedation. Patients who could no longer tolerate CPAP helmets or did not improve with CPAP support were evaluated with anesthetists for programming further management. No initial data on respiratory rate, level of hypoxemia, or oxygen support need (level of PEEP and Fio₂) could discriminate between outcomes.

Prone positioning during CPAP was implemented in 42% of our study population: P/F ratio amelioration after prone positioning was highly variable, ranging from very good P/F ratio improvements to few responses or no response. No significantly greater delta P/F ratio was seen after the first prone positioning cycle in patients who had a positive outcome, probably due to the small size of our population, but we observed a clear positive trend. Interestingly, patients showing a negative outcome had a lower percentage of long-term responses to prone positioning: 6 hours after resupination, they lost the benefit of prone positioning in terms of P/F ratio amelioration. Similarly, a greater number of patients tolerating prone positioning had a positive outcome. These data give insight on the possible benefits of prone positioning in a noninvasively supported cohort of patients, which has been mentioned in previous studies.^30,31

Outcomes and Variables Associated With Negative Outcomes

After correction for age and sex, we found in multiple regression analysis that higher D-dimer and LDH values, lymphopenia, and history of diabetes were independently associated with a worse outcome. Although our results had low statistical significance, we consider the trend of the obtained odds ratios important from a clinical point of view. These results could lead to greater attention being placed on COVID-19 patients who present with these characteristics upon their arrival to the ED because they have increased risk of death or intensive care need. Clinicians should consider SICU admission for these patients in order to guarantee closer monitoring and possibly more aggressive ventilatory treatments, earlier pronation, or earlier transfer to the ICU.

Limitations

The major limitation to our study is undoubtedly its statistical power, due to its relatively low patient population. Particularly, the small number of patients who underwent pronation did not allow speculation about the efficacy of this technique, although preliminary data seem promising. However, ours is among the first studies regarding patients with COVID-19 admitted to a SICU, and these preliminary data truthfully describe the Italian, and perhaps international, experience with the first surge of the pandemic.

Conclusions

Our data highlight the primary role of the SICU in COVID-19 in adequately treating critically ill patients who have high care needs different from intubation, and who require noninvasive ventilation for prolonged times as well as frequent pronation cycles. This setting of care may represent a valid, reliable, and effective option for critically ill respiratory patients. History of diabetes, lymphopenia, and high D-dimer and LDH values are independently associated with negative outcomes, and patients presenting with these characteristics should be strictly monitored.

Acknowledgments: The authors thank the Informatica System S.R.L., as well as Allessando Mendolia for the pro bono creation of the ISCovidCollect data collecting app.

Corresponding author: Sara Abram, MD, via Coppino, 12100 Cuneo, Italy; [email protected].

Disclosures: None.

From the Department of Emergency Medicine, Santa Croce e Carle Hospital, Cuneo, Italy (Drs. Abram, Tosello, Emanuele Bernardi, Allione, Cavalot, Dutto, Corsini, Martini, Sciolla, Sara Bernardi, and Lauria). From the School of Emergency Medicine, University of Turin, Turin, Italy (Drs. Paglietta and Giamello).

Objective: This retrospective and prospective cohort study was designed to describe the characteristics, treatments, and outcomes of patients with SARS-CoV-2 infection (COVID-19) admitted to subintensive care units (SICU) and to identify the variables associated with outcomes. SICUs have been extremely stressed during the pandemic, but most data regarding critically ill COVID-19 patients come from intensive care units (ICUs). Studies about COVID-19 patients in SICUs are lacking.

Setting and participants: The study included 88 COVID-19 patients admitted to our SICU in Cuneo, Italy, between March and May 2020.

Measurements: Clinical and ventilatory data were collected, and patients were divided by outcome. Multivariable logistic regression analysis examined the variables associated with negative outcomes (transfer to the ICU, palliation, or death in a SICU).

Results: A total of 60 patients (68%) had a positive outcome, and 28 patients (32%) had a negative outcome; 69 patients (78%) underwent continuous positive airway pressure (CPAP). Pronation (n = 37 [42%]) had been more frequently adopted in patients who had a positive outcome vs a negative outcome (n = 30 [50%] vs n = 7 [25%]; P = .048), and the median (interquartile range) Pao₂/Fio₂ ratio after 6 hours of prone positioning was lower in patients who had a negative outcome vs a positive outcome (144 [140-168] vs 249 [195-268], P = .006). Independent predictors of a negative outcome were diabetes (odds ratio [OR], 8.22; 95% CI, 1.50-44.70; P = .015), higher D-dimer (OR, 1.28; 95% CI, 1.04-1.57; P = .019), higher lactate dehydrogenase level (OR, 1.003; 95% CI, 1.000-1.006; P = .039), and lower lymphocytes count (OR, 0.996; 95% CI, 0.993-0.999; P = .004).

Conclusion: SICUs have a fundamental role in the treatment of critically ill patients with COVID-19, who require long-term CPAP and pronation cycles. Diabetes, lymphopenia, and high D-dimer and LDH levels are associated with negative outcomes.

Keywords: emergency medicine, noninvasive ventilation, prone position, continuous positive airway pressure.

The COVID-19 pandemic has led to large increases in hospital admissions. Subintensive care units (SICUs) are among the wards most under pressure worldwide,¹ dealing with the increased number of critically ill patients who need noninvasive ventilation, as well as serving as the best alternative to overfilled intensive care units (ICUs). In Italy, SICUs are playing a fundamental role in the management of COVID-19 patients, providing early treatment of respiratory failure by continuous noninvasive ventilation in order to reduce the need for intubation.^2-5 Nevertheless, the great majority of available data about critically ill COVID-19 patients comes from ICUs. Full studies about outcomes of patients in SICUs are lacking and need to be conducted.

We sought to evaluate the characteristics and outcomes of patients admitted to our SICU for COVID-19 to describe the treatments they needed and their impact on prognosis, and to identify the variables associated with patient outcomes.

Methods

Study Design

This cohort study used data from patients who were admitted in the very first weeks of the pandemic. Data were collected retrospectively as well as prospectively, since the ethical committee approved our project. The quality and quantity of data in the 2 groups were comparable.

Data were collected from electronic and written medical records gathered during the patient’s entire stay in our SICU. Data were entered in a database with limited and controlled access. This study complied with the Declaration of Helsinki and was approved by the local ethics committees (ID: MEDURG10).

Study Population

We studied 88 consecutive patients admitted to the SICU of the Santa Croce e Carle Teaching Hospital, Cuneo, Italy, for COVID-19, from March 8 to May 1, 2020. The diagnosis was based on acute respiratory failure associated with SARS-CoV-2 RNA detection on nasopharyngeal swab or tracheal aspirate and/or typical COVID-19 features on a pulmonary computed tomography (CT) scan.⁶ Exclusion criteria were age younger than 18 years and patient denial of permission to use their data for research purposes (the great majority of patients could actively give consent; for patients who were too sick to do so, family members were asked whether they were aware of any reason why the patient would deny consent).

 

 

Clinical Data

The past medical history and recent symptoms description were obtained by manually reviewing medical records. Epidemiological exposure was defined as contact with SARS-CoV-2–positive people or staying in an epidemic outbreak area. Initial vital parameters, venous blood tests, arterial blood gas analysis, chest x-ray, as well as the result of the nasopharyngeal swab were gathered from the emergency department (ED) examination. (Additional swabs could be requested when the first one was negative but clinical suspicion for COVID-19 was high.) Upon admission to the SICU, a standardized panel of blood tests was performed, which was repeated the next day and then every 48 hours. Arterial blood gas analysis was performed when clinically indicated, at least twice a day, or following a scheduled time in patients undergoing pronation. Charlson Comorbidity Index⁷ and MuLBSTA score⁸ were calculated based on the collected data.

Imaging

Chest ultrasonography was performed in the ED at the time of hospitalization and once a day in the SICU. Pulmonary high-resolution computed tomography (HRCT) was performed when clinically indicated or when the results of nasopharyngeal swabs and/or x-ray results were discordant with COVID-19 clinical suspicion. Contrast CT was performed when pulmonary embolism was suspected.

Medical Therapy

Hydroxychloroquine, antiviral agents, tocilizumab, and ruxolitinib were used in the early phase of the pandemic, then were dismissed after evidence of no efficacy.^9-11 Steroids and low-molecular-weight heparin were used afterward. Enoxaparin was used at the standard prophylactic dosage, and 70% of the anticoagulant dosage was also adopted in patients with moderate-to-severe COVID-19 and D-dimer values >3 times the normal value.^12-14 Antibiotics were given when a bacterial superinfection was suspected.

Oxygen and Ventilatory Therapy

Oxygen support or noninvasive ventilation were started based on patients’ respiratory efficacy, estimated by respiratory rate and the ratio of partial pressure of arterial oxygen and fraction of inspired oxygen (P/F ratio).^15,16 Oxygen support was delivered through nasal cannula, Venturi mask, or reservoir mask. Noninvasive ventilation was performed by continuous positive airway pressure (CPAP) when the P/F ratio was <250 or the respiratory rate was >25 breaths per minute, using the helmet interface.^5,17 Prone positioning during CPAP^18-20 was adopted in patients meeting the acute respiratory distress syndrome (ARDS) criteria²¹ and having persistence of respiratory distress and P/F <300 after a 1-hour trial of CPAP.

The prone position was maintained based on patient tolerance. P/F ratio was measured before pronation (T0), after 1 hour of prone position (T1), before resupination (T2), and 6 hours after resupination (T3). With the same timing, the patient was asked to rate their comfort in each position, from 0 (lack of comfort) to 10 (optimal comfort). Delta P/F was defined as the difference between P/F at T3 and basal P/F at T0.

Outcomes

Positive outcomes were defined as patient discharge from the SICU or transfer to a lower-intensity care ward for treatment continuation. Negative outcomes were defined as need for transfer to the ICU, transfer to another ward for palliation, or death in the SICU.

Statistical Analysis

Continuous data are reported as median and interquartile range (IQR); normal distribution of variables was tested using the Shapiro-Wilk test. Categorical variables were reported as absolute number and percentage. The Mann-Whitney test was used to compare continuous variables between groups, and chi-square test with continuity correction was used for categorical variables. The variables that were most significantly associated with a negative outcome on the univariate analysis were included in a stepwise logistic regression analysis, in order to identify independent predictors of patient outcome. Statistical analysis was performed using JASP (JASP Team) software.

 

 

Results

Study Population

Of the 88 patients included in the study, 70% were male; the median age was 66 years (IQR, 60-77). In most patients, the diagnosis of COVID-19 was derived from a positive SARS-CoV-2 nasopharyngeal swab. Six patients, however, maintained a negative swab at all determinations but had clinical and imaging features strongly suggesting COVID-19. No patients met the exclusion criteria. Most patients came from the ED (n = 58 [66%]) or general wards (n = 22 [25%]), while few were transferred from the ICU (n = 8 [9%]). The median length of stay in the SICU was 4 days (IQR, 2-7). An epidemiological link to affected persons or a known virus exposure was identifiable in 37 patients (42%).

Clinical, Laboratory, and Imaging Data

The clinical and anthropometric characteristics of patients are shown in Table 1. Hypertension and smoking habits were prevalent in our population, and the median Charlson Comorbidity Index was 3. Most patients experienced fever, dyspnea, and cough during the days before hospitalization.

Laboratory data showed a marked inflammatory milieu in all studied patients, both at baseline and after 24 and 72 hours. Lymphopenia was observed, along with a significant increase of lactate dehydrogenase (LDH), C-reactive protein (CPR), and D-dimer, and a mild increase of procalcitonin. N-terminal pro-brain natriuretic peptide (NT-proBNP) values were also increased, with normal troponin I values (Table 2).

Medical Therapy

Most patients (89%) received hydroxychloroquine, whereas steroids were used in one-third of the population (36%). Immunomodulators (tocilizumab and ruxolitinib) were restricted to 12 patients (14%). Empirical antiviral therapy was introduced in the first 41 patients (47%). Enoxaparin was the default agent for thromboembolism prophylaxis, and 6 patients (7%) received 70% of the anticoagulating dose.

Oxygen and Ventilatory Therapy

Basal median P/F ratio was 253 (IQR, 218-291), and respiratory rate at triage was 20 breaths/min (IQR, 16-28), underlining a moderate-to-severe respiratory insufficiency at presentation. A total of 69 patients (78%) underwent CPAP, with a median positive end-expiratory pressure (PEEP) of 10.0 cm H₂O (IQR, 7.5-10.0) and fraction of inspired oxygen (Fio₂) of 0.40 (IQR, 0.40-0.50). In 37 patients (42%) who received ongoing CPAP, prone positioning was adopted. In this subgroup, respiratory rate was not significantly different from baseline to resupination (24 vs 25 breaths/min). The median P/F improved from 197 (IQR, 154-236) at baseline to 217 (IQR, 180-262) after pronation (the duration of the prone position was variable, depending on patients’ tolerance: 1 to 6 hours or every pronation cycle). The median delta P/F ratio was 39.4 (IQR, –17.0 to 78.0).

Outcomes

A total of 28 patients (32%) had a negative outcome in the SICU: 8 patients (9%) died, having no clinical indication for higher-intensity care; 6 patients (7%) were transferred to general wards for palliation; and 14 patients (16%) needed an upgrade of cure intensity and were transferred to the ICU. Of these 14 patients, 9 died in the ICU. The total in-hospital mortality of COVID-19 patients, including patients transferred from the SICU to general wards in fair condition, was 27% (n = 24). Clinical, laboratory, and therapeutic characteristics between the 2 groups are shown in Table 4.

Patients who had a negative outcome were significantly older and had more comorbidities, as suggested by a significantly higher prevalence of diabetes and higher Charlson Comorbidity scores (reflecting the mortality risk based on age and comorbidities). The median MuLBSTA score, which estimates the 90-day mortality risk from viral pneumonia, was also higher in patients who had a negative outcome (9.33%). Symptom occurrence was not different in patients with a negative outcome (apart from cough, which was less frequent), but these patients underwent hospitalization earlier—since the appearance of their first COVID-19 symptoms—compared to patients who had a positive outcome. No difference was found in antihypertensive therapy with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers among outcome groups.

More pronounced laboratory abnormalities were found in patients who had a negative outcome, compared to patients who had a positive outcome: lower lymphocytes and higher C-reactive protein (CRP), procalcitonin, D-dimer, LDH, and NT-proBNP. We found no differences in the radiological distribution of pulmonary involvement in patients who had negative or positive outcomes, nor in the adopted medical treatment.

Data showed no difference in CPAP implementation in the 2 groups. However, prone positioning had been more frequently adopted in the group of patients who had a positive outcome, compared with patients who had a negative outcome. No differences of basal P/F were found in patients who had a negative or positive outcome, but the median P/F after 6 hours of prone position was significantly lower in patients who had a negative outcome. The delta P/F ratio did not differ in the 2 groups of patients.

Multivariate Analysis

A logistic regression model was created, including the variables significantly associated with outcomes in the univariate analysis (age, sex, history of diabetes, lymphocytes, CRP, procalcitonin, LDH, NT-proBNP, and D-dimer). In the multivariate analysis, independent predictors of a negative outcome were history of diabetes (odds ratio [OR], 8.22; 95% CI, 1.50-44.70; P =.015), high D-dimer values (OR, 1.28; CI, 1.04-1.57; P = .019), high LDH values (OR, 1.003; CI, 1.000-1.006; P = .039), and low lymphocytes count (OR, 0.996; CI, 0.993-0.999; P = .004).

Discussion

Role of Subintensive Units and Mortality

The novelty of our report is its attempt to investigate the specific group of COVID-19 patients admitted to a SICU. In Italy, SICUs receive acutely ill, spontaneously breathing patients who need (invasive) hemodynamic monitoring, vasoactive medication, renal replacement therapy, chest- tube placement, thrombolysis, and respiratory noninvasive support. The nurse-to-patient ratio is higher than for general wards (usually 1 nurse to every 4 or 5 patients), though lower than for ICUs. In northern Italy, a great number of COVID-19 patients have required this kind of high-intensity care during the pandemic: Noninvasive ventilation support had to be maintained for several days, pronation maneuvers required a high number of people 2 or 3 times a day, and strict monitoring had to be assured. The SICU setting allows patients to buy time as a bridge to progressive reduction of pulmonary involvement, sometimes preventing the need for intubation.

The high prevalence of negative outcomes in the SICU underlines the complexity of COVID-19 patients in this setting. In fact, published data about mortality for patients with severe COVID-19 pneumonia are similar to ours.^22,23

Clinical, Laboratory, and Imaging Data

Our analysis confirmed a high rate of comorbidities in COVID-19 patients²⁴ and their prognostic role with age.^25,26 A marked inflammatory milieu was a negative prognostic indicator, and associated concomitant bacterial superinfection could have led to a worse prognosis (procalcitonin was associated with negative outcomes).²⁷ The cardiovascular system was nevertheless stressed, as suggested by higher values of NT-proBNP in patients with negative outcomes, which could reflect sepsis-related systemic involvement.²⁸

It is known that the pulmonary damage caused by SARS-CoV-2 has a dynamic radiological and clinical course, with early areas of subsegmental consolidation, and bilateral ground-glass opacities predominating later in the course of the disease.²⁹ This could explain why in our population we found no specific radiological pattern leading to a worse outcome.

Medical Therapy

No specific pharmacological therapy was found to be associated with a positive outcome in our study, just like antiviral and immunomodulator therapies failed to demonstrate effectiveness in subsequent pandemic surges. The low statistical power of our study did not allow us to give insight into the effectiveness of steroids and heparin at any dosage.

PEEP Support and Prone Positioning

Continuous positive airway pressure was initiated in the majority of patients and maintained for several days. This was an absolute novelty, because we rarely had to keep patients in helmets for long. This was feasible thanks to the SICU’s high nurse-to-patient ratio and the possibility of providing monitored sedation. Patients who could no longer tolerate CPAP helmets or did not improve with CPAP support were evaluated with anesthetists for programming further management. No initial data on respiratory rate, level of hypoxemia, or oxygen support need (level of PEEP and Fio₂) could discriminate between outcomes.

Prone positioning during CPAP was implemented in 42% of our study population: P/F ratio amelioration after prone positioning was highly variable, ranging from very good P/F ratio improvements to few responses or no response. No significantly greater delta P/F ratio was seen after the first prone positioning cycle in patients who had a positive outcome, probably due to the small size of our population, but we observed a clear positive trend. Interestingly, patients showing a negative outcome had a lower percentage of long-term responses to prone positioning: 6 hours after resupination, they lost the benefit of prone positioning in terms of P/F ratio amelioration. Similarly, a greater number of patients tolerating prone positioning had a positive outcome. These data give insight on the possible benefits of prone positioning in a noninvasively supported cohort of patients, which has been mentioned in previous studies.^30,31

Outcomes and Variables Associated With Negative Outcomes

After correction for age and sex, we found in multiple regression analysis that higher D-dimer and LDH values, lymphopenia, and history of diabetes were independently associated with a worse outcome. Although our results had low statistical significance, we consider the trend of the obtained odds ratios important from a clinical point of view. These results could lead to greater attention being placed on COVID-19 patients who present with these characteristics upon their arrival to the ED because they have increased risk of death or intensive care need. Clinicians should consider SICU admission for these patients in order to guarantee closer monitoring and possibly more aggressive ventilatory treatments, earlier pronation, or earlier transfer to the ICU.

Limitations

The major limitation to our study is undoubtedly its statistical power, due to its relatively low patient population. Particularly, the small number of patients who underwent pronation did not allow speculation about the efficacy of this technique, although preliminary data seem promising. However, ours is among the first studies regarding patients with COVID-19 admitted to a SICU, and these preliminary data truthfully describe the Italian, and perhaps international, experience with the first surge of the pandemic.

Conclusions

Our data highlight the primary role of the SICU in COVID-19 in adequately treating critically ill patients who have high care needs different from intubation, and who require noninvasive ventilation for prolonged times as well as frequent pronation cycles. This setting of care may represent a valid, reliable, and effective option for critically ill respiratory patients. History of diabetes, lymphopenia, and high D-dimer and LDH values are independently associated with negative outcomes, and patients presenting with these characteristics should be strictly monitored.

Acknowledgments: The authors thank the Informatica System S.R.L., as well as Allessando Mendolia for the pro bono creation of the ISCovidCollect data collecting app.

Corresponding author: Sara Abram, MD, via Coppino, 12100 Cuneo, Italy; [email protected].

Disclosures: None.

From the Department of Emergency Medicine, Santa Croce e Carle Hospital, Cuneo, Italy (Drs. Abram, Tosello, Emanuele Bernardi, Allione, Cavalot, Dutto, Corsini, Martini, Sciolla, Sara Bernardi, and Lauria). From the School of Emergency Medicine, University of Turin, Turin, Italy (Drs. Paglietta and Giamello).

Objective: This retrospective and prospective cohort study was designed to describe the characteristics, treatments, and outcomes of patients with SARS-CoV-2 infection (COVID-19) admitted to subintensive care units (SICU) and to identify the variables associated with outcomes. SICUs have been extremely stressed during the pandemic, but most data regarding critically ill COVID-19 patients come from intensive care units (ICUs). Studies about COVID-19 patients in SICUs are lacking.

Setting and participants: The study included 88 COVID-19 patients admitted to our SICU in Cuneo, Italy, between March and May 2020.

Measurements: Clinical and ventilatory data were collected, and patients were divided by outcome. Multivariable logistic regression analysis examined the variables associated with negative outcomes (transfer to the ICU, palliation, or death in a SICU).

Results: A total of 60 patients (68%) had a positive outcome, and 28 patients (32%) had a negative outcome; 69 patients (78%) underwent continuous positive airway pressure (CPAP). Pronation (n = 37 [42%]) had been more frequently adopted in patients who had a positive outcome vs a negative outcome (n = 30 [50%] vs n = 7 [25%]; P = .048), and the median (interquartile range) Pao₂/Fio₂ ratio after 6 hours of prone positioning was lower in patients who had a negative outcome vs a positive outcome (144 [140-168] vs 249 [195-268], P = .006). Independent predictors of a negative outcome were diabetes (odds ratio [OR], 8.22; 95% CI, 1.50-44.70; P = .015), higher D-dimer (OR, 1.28; 95% CI, 1.04-1.57; P = .019), higher lactate dehydrogenase level (OR, 1.003; 95% CI, 1.000-1.006; P = .039), and lower lymphocytes count (OR, 0.996; 95% CI, 0.993-0.999; P = .004).

Conclusion: SICUs have a fundamental role in the treatment of critically ill patients with COVID-19, who require long-term CPAP and pronation cycles. Diabetes, lymphopenia, and high D-dimer and LDH levels are associated with negative outcomes.

Keywords: emergency medicine, noninvasive ventilation, prone position, continuous positive airway pressure.

The COVID-19 pandemic has led to large increases in hospital admissions. Subintensive care units (SICUs) are among the wards most under pressure worldwide,¹ dealing with the increased number of critically ill patients who need noninvasive ventilation, as well as serving as the best alternative to overfilled intensive care units (ICUs). In Italy, SICUs are playing a fundamental role in the management of COVID-19 patients, providing early treatment of respiratory failure by continuous noninvasive ventilation in order to reduce the need for intubation.^2-5 Nevertheless, the great majority of available data about critically ill COVID-19 patients comes from ICUs. Full studies about outcomes of patients in SICUs are lacking and need to be conducted.

We sought to evaluate the characteristics and outcomes of patients admitted to our SICU for COVID-19 to describe the treatments they needed and their impact on prognosis, and to identify the variables associated with patient outcomes.

Methods

Study Design

This cohort study used data from patients who were admitted in the very first weeks of the pandemic. Data were collected retrospectively as well as prospectively, since the ethical committee approved our project. The quality and quantity of data in the 2 groups were comparable.

Data were collected from electronic and written medical records gathered during the patient’s entire stay in our SICU. Data were entered in a database with limited and controlled access. This study complied with the Declaration of Helsinki and was approved by the local ethics committees (ID: MEDURG10).

Study Population

We studied 88 consecutive patients admitted to the SICU of the Santa Croce e Carle Teaching Hospital, Cuneo, Italy, for COVID-19, from March 8 to May 1, 2020. The diagnosis was based on acute respiratory failure associated with SARS-CoV-2 RNA detection on nasopharyngeal swab or tracheal aspirate and/or typical COVID-19 features on a pulmonary computed tomography (CT) scan.⁶ Exclusion criteria were age younger than 18 years and patient denial of permission to use their data for research purposes (the great majority of patients could actively give consent; for patients who were too sick to do so, family members were asked whether they were aware of any reason why the patient would deny consent).

 

 

Clinical Data

The past medical history and recent symptoms description were obtained by manually reviewing medical records. Epidemiological exposure was defined as contact with SARS-CoV-2–positive people or staying in an epidemic outbreak area. Initial vital parameters, venous blood tests, arterial blood gas analysis, chest x-ray, as well as the result of the nasopharyngeal swab were gathered from the emergency department (ED) examination. (Additional swabs could be requested when the first one was negative but clinical suspicion for COVID-19 was high.) Upon admission to the SICU, a standardized panel of blood tests was performed, which was repeated the next day and then every 48 hours. Arterial blood gas analysis was performed when clinically indicated, at least twice a day, or following a scheduled time in patients undergoing pronation. Charlson Comorbidity Index⁷ and MuLBSTA score⁸ were calculated based on the collected data.

Imaging

Chest ultrasonography was performed in the ED at the time of hospitalization and once a day in the SICU. Pulmonary high-resolution computed tomography (HRCT) was performed when clinically indicated or when the results of nasopharyngeal swabs and/or x-ray results were discordant with COVID-19 clinical suspicion. Contrast CT was performed when pulmonary embolism was suspected.

Medical Therapy

Hydroxychloroquine, antiviral agents, tocilizumab, and ruxolitinib were used in the early phase of the pandemic, then were dismissed after evidence of no efficacy.^9-11 Steroids and low-molecular-weight heparin were used afterward. Enoxaparin was used at the standard prophylactic dosage, and 70% of the anticoagulant dosage was also adopted in patients with moderate-to-severe COVID-19 and D-dimer values >3 times the normal value.^12-14 Antibiotics were given when a bacterial superinfection was suspected.

Oxygen and Ventilatory Therapy

Oxygen support or noninvasive ventilation were started based on patients’ respiratory efficacy, estimated by respiratory rate and the ratio of partial pressure of arterial oxygen and fraction of inspired oxygen (P/F ratio).^15,16 Oxygen support was delivered through nasal cannula, Venturi mask, or reservoir mask. Noninvasive ventilation was performed by continuous positive airway pressure (CPAP) when the P/F ratio was <250 or the respiratory rate was >25 breaths per minute, using the helmet interface.^5,17 Prone positioning during CPAP^18-20 was adopted in patients meeting the acute respiratory distress syndrome (ARDS) criteria²¹ and having persistence of respiratory distress and P/F <300 after a 1-hour trial of CPAP.

The prone position was maintained based on patient tolerance. P/F ratio was measured before pronation (T0), after 1 hour of prone position (T1), before resupination (T2), and 6 hours after resupination (T3). With the same timing, the patient was asked to rate their comfort in each position, from 0 (lack of comfort) to 10 (optimal comfort). Delta P/F was defined as the difference between P/F at T3 and basal P/F at T0.

Outcomes

Positive outcomes were defined as patient discharge from the SICU or transfer to a lower-intensity care ward for treatment continuation. Negative outcomes were defined as need for transfer to the ICU, transfer to another ward for palliation, or death in the SICU.

Statistical Analysis

Continuous data are reported as median and interquartile range (IQR); normal distribution of variables was tested using the Shapiro-Wilk test. Categorical variables were reported as absolute number and percentage. The Mann-Whitney test was used to compare continuous variables between groups, and chi-square test with continuity correction was used for categorical variables. The variables that were most significantly associated with a negative outcome on the univariate analysis were included in a stepwise logistic regression analysis, in order to identify independent predictors of patient outcome. Statistical analysis was performed using JASP (JASP Team) software.

 

 

Results

Study Population

Of the 88 patients included in the study, 70% were male; the median age was 66 years (IQR, 60-77). In most patients, the diagnosis of COVID-19 was derived from a positive SARS-CoV-2 nasopharyngeal swab. Six patients, however, maintained a negative swab at all determinations but had clinical and imaging features strongly suggesting COVID-19. No patients met the exclusion criteria. Most patients came from the ED (n = 58 [66%]) or general wards (n = 22 [25%]), while few were transferred from the ICU (n = 8 [9%]). The median length of stay in the SICU was 4 days (IQR, 2-7). An epidemiological link to affected persons or a known virus exposure was identifiable in 37 patients (42%).

Clinical, Laboratory, and Imaging Data

The clinical and anthropometric characteristics of patients are shown in Table 1. Hypertension and smoking habits were prevalent in our population, and the median Charlson Comorbidity Index was 3. Most patients experienced fever, dyspnea, and cough during the days before hospitalization.

Laboratory data showed a marked inflammatory milieu in all studied patients, both at baseline and after 24 and 72 hours. Lymphopenia was observed, along with a significant increase of lactate dehydrogenase (LDH), C-reactive protein (CPR), and D-dimer, and a mild increase of procalcitonin. N-terminal pro-brain natriuretic peptide (NT-proBNP) values were also increased, with normal troponin I values (Table 2).

Medical Therapy

Most patients (89%) received hydroxychloroquine, whereas steroids were used in one-third of the population (36%). Immunomodulators (tocilizumab and ruxolitinib) were restricted to 12 patients (14%). Empirical antiviral therapy was introduced in the first 41 patients (47%). Enoxaparin was the default agent for thromboembolism prophylaxis, and 6 patients (7%) received 70% of the anticoagulating dose.

Oxygen and Ventilatory Therapy

Basal median P/F ratio was 253 (IQR, 218-291), and respiratory rate at triage was 20 breaths/min (IQR, 16-28), underlining a moderate-to-severe respiratory insufficiency at presentation. A total of 69 patients (78%) underwent CPAP, with a median positive end-expiratory pressure (PEEP) of 10.0 cm H₂O (IQR, 7.5-10.0) and fraction of inspired oxygen (Fio₂) of 0.40 (IQR, 0.40-0.50). In 37 patients (42%) who received ongoing CPAP, prone positioning was adopted. In this subgroup, respiratory rate was not significantly different from baseline to resupination (24 vs 25 breaths/min). The median P/F improved from 197 (IQR, 154-236) at baseline to 217 (IQR, 180-262) after pronation (the duration of the prone position was variable, depending on patients’ tolerance: 1 to 6 hours or every pronation cycle). The median delta P/F ratio was 39.4 (IQR, –17.0 to 78.0).

Outcomes

A total of 28 patients (32%) had a negative outcome in the SICU: 8 patients (9%) died, having no clinical indication for higher-intensity care; 6 patients (7%) were transferred to general wards for palliation; and 14 patients (16%) needed an upgrade of cure intensity and were transferred to the ICU. Of these 14 patients, 9 died in the ICU. The total in-hospital mortality of COVID-19 patients, including patients transferred from the SICU to general wards in fair condition, was 27% (n = 24). Clinical, laboratory, and therapeutic characteristics between the 2 groups are shown in Table 4.

Patients who had a negative outcome were significantly older and had more comorbidities, as suggested by a significantly higher prevalence of diabetes and higher Charlson Comorbidity scores (reflecting the mortality risk based on age and comorbidities). The median MuLBSTA score, which estimates the 90-day mortality risk from viral pneumonia, was also higher in patients who had a negative outcome (9.33%). Symptom occurrence was not different in patients with a negative outcome (apart from cough, which was less frequent), but these patients underwent hospitalization earlier—since the appearance of their first COVID-19 symptoms—compared to patients who had a positive outcome. No difference was found in antihypertensive therapy with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers among outcome groups.

More pronounced laboratory abnormalities were found in patients who had a negative outcome, compared to patients who had a positive outcome: lower lymphocytes and higher C-reactive protein (CRP), procalcitonin, D-dimer, LDH, and NT-proBNP. We found no differences in the radiological distribution of pulmonary involvement in patients who had negative or positive outcomes, nor in the adopted medical treatment.

Data showed no difference in CPAP implementation in the 2 groups. However, prone positioning had been more frequently adopted in the group of patients who had a positive outcome, compared with patients who had a negative outcome. No differences of basal P/F were found in patients who had a negative or positive outcome, but the median P/F after 6 hours of prone position was significantly lower in patients who had a negative outcome. The delta P/F ratio did not differ in the 2 groups of patients.

Multivariate Analysis

A logistic regression model was created, including the variables significantly associated with outcomes in the univariate analysis (age, sex, history of diabetes, lymphocytes, CRP, procalcitonin, LDH, NT-proBNP, and D-dimer). In the multivariate analysis, independent predictors of a negative outcome were history of diabetes (odds ratio [OR], 8.22; 95% CI, 1.50-44.70; P =.015), high D-dimer values (OR, 1.28; CI, 1.04-1.57; P = .019), high LDH values (OR, 1.003; CI, 1.000-1.006; P = .039), and low lymphocytes count (OR, 0.996; CI, 0.993-0.999; P = .004).

Discussion

Role of Subintensive Units and Mortality

The novelty of our report is its attempt to investigate the specific group of COVID-19 patients admitted to a SICU. In Italy, SICUs receive acutely ill, spontaneously breathing patients who need (invasive) hemodynamic monitoring, vasoactive medication, renal replacement therapy, chest- tube placement, thrombolysis, and respiratory noninvasive support. The nurse-to-patient ratio is higher than for general wards (usually 1 nurse to every 4 or 5 patients), though lower than for ICUs. In northern Italy, a great number of COVID-19 patients have required this kind of high-intensity care during the pandemic: Noninvasive ventilation support had to be maintained for several days, pronation maneuvers required a high number of people 2 or 3 times a day, and strict monitoring had to be assured. The SICU setting allows patients to buy time as a bridge to progressive reduction of pulmonary involvement, sometimes preventing the need for intubation.

The high prevalence of negative outcomes in the SICU underlines the complexity of COVID-19 patients in this setting. In fact, published data about mortality for patients with severe COVID-19 pneumonia are similar to ours.^22,23

Clinical, Laboratory, and Imaging Data

Our analysis confirmed a high rate of comorbidities in COVID-19 patients²⁴ and their prognostic role with age.^25,26 A marked inflammatory milieu was a negative prognostic indicator, and associated concomitant bacterial superinfection could have led to a worse prognosis (procalcitonin was associated with negative outcomes).²⁷ The cardiovascular system was nevertheless stressed, as suggested by higher values of NT-proBNP in patients with negative outcomes, which could reflect sepsis-related systemic involvement.²⁸

It is known that the pulmonary damage caused by SARS-CoV-2 has a dynamic radiological and clinical course, with early areas of subsegmental consolidation, and bilateral ground-glass opacities predominating later in the course of the disease.²⁹ This could explain why in our population we found no specific radiological pattern leading to a worse outcome.

Medical Therapy

No specific pharmacological therapy was found to be associated with a positive outcome in our study, just like antiviral and immunomodulator therapies failed to demonstrate effectiveness in subsequent pandemic surges. The low statistical power of our study did not allow us to give insight into the effectiveness of steroids and heparin at any dosage.

PEEP Support and Prone Positioning

Continuous positive airway pressure was initiated in the majority of patients and maintained for several days. This was an absolute novelty, because we rarely had to keep patients in helmets for long. This was feasible thanks to the SICU’s high nurse-to-patient ratio and the possibility of providing monitored sedation. Patients who could no longer tolerate CPAP helmets or did not improve with CPAP support were evaluated with anesthetists for programming further management. No initial data on respiratory rate, level of hypoxemia, or oxygen support need (level of PEEP and Fio₂) could discriminate between outcomes.

Prone positioning during CPAP was implemented in 42% of our study population: P/F ratio amelioration after prone positioning was highly variable, ranging from very good P/F ratio improvements to few responses or no response. No significantly greater delta P/F ratio was seen after the first prone positioning cycle in patients who had a positive outcome, probably due to the small size of our population, but we observed a clear positive trend. Interestingly, patients showing a negative outcome had a lower percentage of long-term responses to prone positioning: 6 hours after resupination, they lost the benefit of prone positioning in terms of P/F ratio amelioration. Similarly, a greater number of patients tolerating prone positioning had a positive outcome. These data give insight on the possible benefits of prone positioning in a noninvasively supported cohort of patients, which has been mentioned in previous studies.^30,31

Outcomes and Variables Associated With Negative Outcomes

After correction for age and sex, we found in multiple regression analysis that higher D-dimer and LDH values, lymphopenia, and history of diabetes were independently associated with a worse outcome. Although our results had low statistical significance, we consider the trend of the obtained odds ratios important from a clinical point of view. These results could lead to greater attention being placed on COVID-19 patients who present with these characteristics upon their arrival to the ED because they have increased risk of death or intensive care need. Clinicians should consider SICU admission for these patients in order to guarantee closer monitoring and possibly more aggressive ventilatory treatments, earlier pronation, or earlier transfer to the ICU.

Limitations

The major limitation to our study is undoubtedly its statistical power, due to its relatively low patient population. Particularly, the small number of patients who underwent pronation did not allow speculation about the efficacy of this technique, although preliminary data seem promising. However, ours is among the first studies regarding patients with COVID-19 admitted to a SICU, and these preliminary data truthfully describe the Italian, and perhaps international, experience with the first surge of the pandemic.

Conclusions

Our data highlight the primary role of the SICU in COVID-19 in adequately treating critically ill patients who have high care needs different from intubation, and who require noninvasive ventilation for prolonged times as well as frequent pronation cycles. This setting of care may represent a valid, reliable, and effective option for critically ill respiratory patients. History of diabetes, lymphopenia, and high D-dimer and LDH values are independently associated with negative outcomes, and patients presenting with these characteristics should be strictly monitored.

Acknowledgments: The authors thank the Informatica System S.R.L., as well as Allessando Mendolia for the pro bono creation of the ISCovidCollect data collecting app.

Corresponding author: Sara Abram, MD, via Coppino, 12100 Cuneo, Italy; [email protected].

Disclosures: None.

Equitable Standards for All Patients in a Crisis

Health care delivered during a pandemic instantiates medicine’s perspectives on the value of human life in clinical scenarios where resource allocation is limited. The COVID-19 pandemic has fostered dialogue and debate around the ethical principles that underly such resource allocation, which generally balance (1) utilitarian optimization of resources, (2) equality or equity in health access, (3) the instrumental value of individuals as agents in society, and (4) prioritizing the “worst off” in their natural history of disease.^1,2 State legislatures and health systems have responded to the challeges posed by COVID-19 by considering both the scarcity of intensive care resources, such as mechanical ventilation and hemodialysis, and the clinical criteria to be used for determining which patients should receive said resources. These crisis guidelines have yielded several concerning themes vis-à-vis equitable distribution of health care resources, particularly when the disability status of patients is considered alongside life-expectancy or quality of life.³

Crisis standards of care (CSC) prioritize population-level health under a utilitarian paradigm, explicitly maximizing “life-years” within a population of patients rather than the life of any individual patient.⁴ Debated during initial COVID surges, these CSC guidelines have recently been enacted at the state level in several settings, including Alaska and Idaho.⁵ In a setting with scarce intensive care resources, balancing health equity in access to these resources against population-based survival metrics has been a challenge for commissions considering CSC.^6,7 This need for balance has further promoted systemic views of “disability,” raising concern for structural “ableism” and highlighting the need for greater “ability awareness” in clinicians’ continued professional learning.

Structural Ableism: Defining Perspectives to Address Health Equity

Ableism has been defined as “a system that places value on people’s bodies and minds, based on societally constructed ideas of normalcy, intelligence, excellence, and productivity…[and] leads to people and society determining who is valuable and worthy based on their appearance and/or their ability to satisfactorily [re]produce, excel, and ‘behave.’”⁸ Regarding CSC, concerns about systemic bias in guideline design were raised early by disability advocacy groups during comment periods.^9,10 More broadly, concerns about ableism sit alongside many deeply rooted societal perspectives of disabled individuals as pitiable or, conversely, heroic for having “overcome” their disability in some way. As a physician who sits in a manual wheelchair with paraplegia and mobility impairment, I have equally been subject to inappropriate bias and inappropriate praise for living in a wheelchair. I have also wondered, alongside my patients living with different levels of mobility or ability, why others often view us as “worse off.” Addressing directly whether disabled individuals are “worse off,” disability rights attorney and advocate Harriet McBryde Johnson has articulated a predominant sentiment among persons living with unique or different abilities:

Are we “worse off”? I don’t think so. Not in any meaningful way. There are too many variables. For those of us with congenital conditions, disability shapes all we are. Those disabled later in life adapt. We take constraints that no one would choose and build rich and satisfying lives within them. We enjoy pleasures other people enjoy and pleasures peculiarly our own. We have something the world needs.¹¹

Many physician colleagues have common, invisible diseases such as diabetes and heart disease; fewer colleagues share conditions that are as visible as my spinal cord injury, as readily apparent to patients upon my entry to their hospital rooms. This simultaneous and inescapable identity as both patient and provider has afforded me wonderful doctor-patient interactions, particularly with those patients who appreciate how my patient experience impacts my ability to partially understand theirs. However, this simultaneous identity as doctor and patient also informed my personal and professional concerns regarding structural ableism as I considered scoring my own acutely ill hospital medicine patients with CSC triage scores in April 2020.

As a practicing hospital medicine physician, I have been emboldened by the efforts of my fellow clinicians amid COVID-19; their efforts have reaffirmed all the reasons I pursued a career in medicine. However, when I heard my clinical colleagues’ first explanation of the Massachusetts CSC guidelines in April 2020, I raised my hand to ask whether the “life-years” to which the guidelines referred were quality-adjusted. My concern regarding the implicit use of quality-adjusted life years (QALY) or disability-adjusted life years in clinical decision-making and implementation of these guidelines was validated when no clinical leaders could address this question directly. Sitting on the CSC committee for my hospital during this time was an honor. However, it was disconcerting to hear many clinicians’ unease when estimating mean survival for common chronic diseases, ranging from end-stage renal disease to advanced heart failure. If my expert colleagues, clinical specialists in kidney and heart disease, could not confidently apply mean survival estimates to multimorbid hospital patients, then idiosyncratic clinical judgment was sure to have a heavy hand in any calculation of “life-years.” Thus, my primary concern was that clinicians using triage heuristics would be subject to bias, regardless of their intention, and negatively adjust for the quality of a disabled life in their CSC triage scoring. My secondary concern was that the CSC guidelines themselves included systemic bias against disabled individuals.

According to CSC schema, triage scores index heavily on Sequential Organ Failure Assessment (SOFA) scores to define short-term survival; SOFA scores are partially driven by the Glasgow Coma Scale (GCS). Following professional and public comment periods, CSC guidelines in Massachusetts were revised to, among other critical points of revision, change prognostic estimation via “life years” in favor of generic estimation of short-term survival (Table). I wondered, if I presented to an emergency department with severe COVID-19 and was scored with the GCS for the purpose of making a CSC ventilator triage decision, how would my complete paraplegia and lower-extremity motor impairment be accounted for by a clinician assessing “best motor response” in the GCS? The purpose of these scores is to act algorithmically, to guide clinicians whose cognitive load and time limitations may not allow for adjustment of these algorithms based on the individual patient in front of them. Individualization of clinical decisions is part of medicine’s art, but is difficult in the best of times and no easier during a crisis in care delivery. As CSC triage scores were amended and addended throughout 2020, I returned to the COVID wards, time and again wondering, “What have we learned about systemic bias and health inequity in the CSC process and the pandemic broadly, with specific regard to disability?”

Ability Awareness: Room for Our Improvement

Unfortunately, there is reason to believe that clinical judgment is impaired by structural ableism. In seminal work on this topic, Gerhart et al¹² demonstrated that clinicians considered spinal cord injury (SCI) survivors to have low self-perceptions of worthiness, overall negative attitudes, and low self-esteem as compared to able-bodied individuals. However, surveyed SCI survivors generally had similar self-perceptions of worth and positivity as compared to ”able-bodied” clinicians.¹² For providers who care for persons with disabilities, the majority (82.4%) have rated their disabled patients’ quality of life as worse.¹³ It is no wonder that patients with disabilities are more likely to feel that their doctor-patient relationship is impacted by lack of understanding, negative sentiment, or simple lack of listening.¹⁴ Generally, this poor doctor-patient relationship with disabled patients is exacerbated by poor exposure of medical trainees to disability education; only 34.2% of internal medicine residents recall any form of disability education in medical school, while only 52% of medical school deans report having disability educational content in their curricula.^15,16 There is a similar lack of disability representation in the population of medical trainees themselves. While approximately 20% of the American population lives with a disability, less than 2% of American medical students have a disability.^17-19

While representation of disabled populations in medical practice remains poor, disabled patients are generally less likely to receive age-appropriate prevention, appropriate access to care, and equal access to treatment.^20-22 “Diagnostic overshadowing” refers to clinicians’ attribution of nonspecific signs or symptoms to a patient’s chronic disability as opposed to acute illness.²³ This phenomenon has led to higher rates of preventable malignancy in disabled patients and misattribution of common somatic symptoms to intellectual disability.^24,25 With this disparity in place as status quo for health care delivery to disabled populations, it is no surprise that certain portions of the disabled population have accounted for disproportionate mortality due to COVID-19.^26,27Disability advocates have called for “nothing about us without us,” a phrase associated with the United Nations Convention on the Rights of Persons with Disabilities. Understanding the profound neurodiversity among several forms of sensory and cognitive disabilities, as well as the functional difference between cognitive disabilities, mobility impairment, and inability to meet one’s instrumental activities of daily living independently, others have proposed a unique approach to certain disabled populations in COVID care.²⁸ My own perspective is that definite progress may require a more general understanding of the prevalence of disability by clinicians, both via medical training and by directly addressing health equity for disabled populations in such calculations as the CSC. Systemic ableism is apparent in our most common clinical scoring systems, ranging from the GCS and Functional Assessment Staging Table to the Eastern Cooperative Oncology Group and Karnofsky Performance Status scales. I have reexamined these scoring systems in my own understanding given their general equation of ambulation with ability or normalcy. As a doctor in a manual wheelchair who values greatly my personal quality of life and professional contribution to patient care, I worry that these scoring systems inherently discount my own equitable access to care. Individualization of patients’ particular abilities in the context of these scales must occur alongside evidence-based, guideline-directed management via these scoring systems.

Conclusion: Future Orientation

Updated CSC guidelines have accounted for the unique considerations of disabled patients by effectively caveating their scoring algorithms, directing clinicians via disclaimers to uniquely consider their disabled patients in clinical judgement. This is a first step, but it is also one that erodes the value of algorithms, which generally obviate more deliberative thinking and individualization. For our patients who lack certain abilities, as CSC continue to be activated in several states, we have an opportunity to pursue more inherently equitable solutions before further suffering accrues.²⁹ By way of example, adaptations to scoring systems that leverage QALYs for value-based drug pricing indices have been proposed by organizations like the Institute for Clinical and Economic Review, which proposed the Equal-Value-of Life-Years-Gained framework to inform QALY-based arbitration of drug pricing.³⁰ This is not a perfect rubric but instead represents an attempt to balance consideration of drugs, as has been done with ventilators during the pandemic, as a scare and expensive resource while addressing the just concerns of advocacy groups in structural ableism.

Resource stewardship during a crisis should not discount those states of human life that are perceived to be less desirable, particularly if they are not experienced as less desirable but are experienced uniquely. Instead, we should consider equitably measuring our intervention to match a patient’s needs, as we would dose-adjust a medication for renal function or consider minimally invasive procedures for multimorbid patients. COVID-19 has reflected our profession’s ethical adaptation during crisis as resources have become scarce; there is no better time to define solutions for health equity. We should now be concerned equally by the influence our personal biases have on our clinical practice and by the way in which these crisis standards will influence patients’ perception of and trust in their care providers during periods of perceived plentiful resources in the future. Health care resources are always limited, allocated according to societal values; if we value health equity for people of all abilities, then we will consider these abilities equitably as we pursue new standards for health care delivery.

Corresponding author: Gregory D. Snyder, MD, MBA, 2014 Washington Street, Newton, MA 02462; [email protected].

Disclosures: None.
 

Equitable Standards for All Patients in a Crisis

Health care delivered during a pandemic instantiates medicine’s perspectives on the value of human life in clinical scenarios where resource allocation is limited. The COVID-19 pandemic has fostered dialogue and debate around the ethical principles that underly such resource allocation, which generally balance (1) utilitarian optimization of resources, (2) equality or equity in health access, (3) the instrumental value of individuals as agents in society, and (4) prioritizing the “worst off” in their natural history of disease.^1,2 State legislatures and health systems have responded to the challeges posed by COVID-19 by considering both the scarcity of intensive care resources, such as mechanical ventilation and hemodialysis, and the clinical criteria to be used for determining which patients should receive said resources. These crisis guidelines have yielded several concerning themes vis-à-vis equitable distribution of health care resources, particularly when the disability status of patients is considered alongside life-expectancy or quality of life.³

Crisis standards of care (CSC) prioritize population-level health under a utilitarian paradigm, explicitly maximizing “life-years” within a population of patients rather than the life of any individual patient.⁴ Debated during initial COVID surges, these CSC guidelines have recently been enacted at the state level in several settings, including Alaska and Idaho.⁵ In a setting with scarce intensive care resources, balancing health equity in access to these resources against population-based survival metrics has been a challenge for commissions considering CSC.^6,7 This need for balance has further promoted systemic views of “disability,” raising concern for structural “ableism” and highlighting the need for greater “ability awareness” in clinicians’ continued professional learning.

Structural Ableism: Defining Perspectives to Address Health Equity

Ableism has been defined as “a system that places value on people’s bodies and minds, based on societally constructed ideas of normalcy, intelligence, excellence, and productivity…[and] leads to people and society determining who is valuable and worthy based on their appearance and/or their ability to satisfactorily [re]produce, excel, and ‘behave.’”⁸ Regarding CSC, concerns about systemic bias in guideline design were raised early by disability advocacy groups during comment periods.^9,10 More broadly, concerns about ableism sit alongside many deeply rooted societal perspectives of disabled individuals as pitiable or, conversely, heroic for having “overcome” their disability in some way. As a physician who sits in a manual wheelchair with paraplegia and mobility impairment, I have equally been subject to inappropriate bias and inappropriate praise for living in a wheelchair. I have also wondered, alongside my patients living with different levels of mobility or ability, why others often view us as “worse off.” Addressing directly whether disabled individuals are “worse off,” disability rights attorney and advocate Harriet McBryde Johnson has articulated a predominant sentiment among persons living with unique or different abilities:

Are we “worse off”? I don’t think so. Not in any meaningful way. There are too many variables. For those of us with congenital conditions, disability shapes all we are. Those disabled later in life adapt. We take constraints that no one would choose and build rich and satisfying lives within them. We enjoy pleasures other people enjoy and pleasures peculiarly our own. We have something the world needs.¹¹

Many physician colleagues have common, invisible diseases such as diabetes and heart disease; fewer colleagues share conditions that are as visible as my spinal cord injury, as readily apparent to patients upon my entry to their hospital rooms. This simultaneous and inescapable identity as both patient and provider has afforded me wonderful doctor-patient interactions, particularly with those patients who appreciate how my patient experience impacts my ability to partially understand theirs. However, this simultaneous identity as doctor and patient also informed my personal and professional concerns regarding structural ableism as I considered scoring my own acutely ill hospital medicine patients with CSC triage scores in April 2020.

As a practicing hospital medicine physician, I have been emboldened by the efforts of my fellow clinicians amid COVID-19; their efforts have reaffirmed all the reasons I pursued a career in medicine. However, when I heard my clinical colleagues’ first explanation of the Massachusetts CSC guidelines in April 2020, I raised my hand to ask whether the “life-years” to which the guidelines referred were quality-adjusted. My concern regarding the implicit use of quality-adjusted life years (QALY) or disability-adjusted life years in clinical decision-making and implementation of these guidelines was validated when no clinical leaders could address this question directly. Sitting on the CSC committee for my hospital during this time was an honor. However, it was disconcerting to hear many clinicians’ unease when estimating mean survival for common chronic diseases, ranging from end-stage renal disease to advanced heart failure. If my expert colleagues, clinical specialists in kidney and heart disease, could not confidently apply mean survival estimates to multimorbid hospital patients, then idiosyncratic clinical judgment was sure to have a heavy hand in any calculation of “life-years.” Thus, my primary concern was that clinicians using triage heuristics would be subject to bias, regardless of their intention, and negatively adjust for the quality of a disabled life in their CSC triage scoring. My secondary concern was that the CSC guidelines themselves included systemic bias against disabled individuals.

According to CSC schema, triage scores index heavily on Sequential Organ Failure Assessment (SOFA) scores to define short-term survival; SOFA scores are partially driven by the Glasgow Coma Scale (GCS). Following professional and public comment periods, CSC guidelines in Massachusetts were revised to, among other critical points of revision, change prognostic estimation via “life years” in favor of generic estimation of short-term survival (Table). I wondered, if I presented to an emergency department with severe COVID-19 and was scored with the GCS for the purpose of making a CSC ventilator triage decision, how would my complete paraplegia and lower-extremity motor impairment be accounted for by a clinician assessing “best motor response” in the GCS? The purpose of these scores is to act algorithmically, to guide clinicians whose cognitive load and time limitations may not allow for adjustment of these algorithms based on the individual patient in front of them. Individualization of clinical decisions is part of medicine’s art, but is difficult in the best of times and no easier during a crisis in care delivery. As CSC triage scores were amended and addended throughout 2020, I returned to the COVID wards, time and again wondering, “What have we learned about systemic bias and health inequity in the CSC process and the pandemic broadly, with specific regard to disability?”

Ability Awareness: Room for Our Improvement

Unfortunately, there is reason to believe that clinical judgment is impaired by structural ableism. In seminal work on this topic, Gerhart et al¹² demonstrated that clinicians considered spinal cord injury (SCI) survivors to have low self-perceptions of worthiness, overall negative attitudes, and low self-esteem as compared to able-bodied individuals. However, surveyed SCI survivors generally had similar self-perceptions of worth and positivity as compared to ”able-bodied” clinicians.¹² For providers who care for persons with disabilities, the majority (82.4%) have rated their disabled patients’ quality of life as worse.¹³ It is no wonder that patients with disabilities are more likely to feel that their doctor-patient relationship is impacted by lack of understanding, negative sentiment, or simple lack of listening.¹⁴ Generally, this poor doctor-patient relationship with disabled patients is exacerbated by poor exposure of medical trainees to disability education; only 34.2% of internal medicine residents recall any form of disability education in medical school, while only 52% of medical school deans report having disability educational content in their curricula.^15,16 There is a similar lack of disability representation in the population of medical trainees themselves. While approximately 20% of the American population lives with a disability, less than 2% of American medical students have a disability.^17-19

While representation of disabled populations in medical practice remains poor, disabled patients are generally less likely to receive age-appropriate prevention, appropriate access to care, and equal access to treatment.^20-22 “Diagnostic overshadowing” refers to clinicians’ attribution of nonspecific signs or symptoms to a patient’s chronic disability as opposed to acute illness.²³ This phenomenon has led to higher rates of preventable malignancy in disabled patients and misattribution of common somatic symptoms to intellectual disability.^24,25 With this disparity in place as status quo for health care delivery to disabled populations, it is no surprise that certain portions of the disabled population have accounted for disproportionate mortality due to COVID-19.^26,27Disability advocates have called for “nothing about us without us,” a phrase associated with the United Nations Convention on the Rights of Persons with Disabilities. Understanding the profound neurodiversity among several forms of sensory and cognitive disabilities, as well as the functional difference between cognitive disabilities, mobility impairment, and inability to meet one’s instrumental activities of daily living independently, others have proposed a unique approach to certain disabled populations in COVID care.²⁸ My own perspective is that definite progress may require a more general understanding of the prevalence of disability by clinicians, both via medical training and by directly addressing health equity for disabled populations in such calculations as the CSC. Systemic ableism is apparent in our most common clinical scoring systems, ranging from the GCS and Functional Assessment Staging Table to the Eastern Cooperative Oncology Group and Karnofsky Performance Status scales. I have reexamined these scoring systems in my own understanding given their general equation of ambulation with ability or normalcy. As a doctor in a manual wheelchair who values greatly my personal quality of life and professional contribution to patient care, I worry that these scoring systems inherently discount my own equitable access to care. Individualization of patients’ particular abilities in the context of these scales must occur alongside evidence-based, guideline-directed management via these scoring systems.

Conclusion: Future Orientation

Updated CSC guidelines have accounted for the unique considerations of disabled patients by effectively caveating their scoring algorithms, directing clinicians via disclaimers to uniquely consider their disabled patients in clinical judgement. This is a first step, but it is also one that erodes the value of algorithms, which generally obviate more deliberative thinking and individualization. For our patients who lack certain abilities, as CSC continue to be activated in several states, we have an opportunity to pursue more inherently equitable solutions before further suffering accrues.²⁹ By way of example, adaptations to scoring systems that leverage QALYs for value-based drug pricing indices have been proposed by organizations like the Institute for Clinical and Economic Review, which proposed the Equal-Value-of Life-Years-Gained framework to inform QALY-based arbitration of drug pricing.³⁰ This is not a perfect rubric but instead represents an attempt to balance consideration of drugs, as has been done with ventilators during the pandemic, as a scare and expensive resource while addressing the just concerns of advocacy groups in structural ableism.

Resource stewardship during a crisis should not discount those states of human life that are perceived to be less desirable, particularly if they are not experienced as less desirable but are experienced uniquely. Instead, we should consider equitably measuring our intervention to match a patient’s needs, as we would dose-adjust a medication for renal function or consider minimally invasive procedures for multimorbid patients. COVID-19 has reflected our profession’s ethical adaptation during crisis as resources have become scarce; there is no better time to define solutions for health equity. We should now be concerned equally by the influence our personal biases have on our clinical practice and by the way in which these crisis standards will influence patients’ perception of and trust in their care providers during periods of perceived plentiful resources in the future. Health care resources are always limited, allocated according to societal values; if we value health equity for people of all abilities, then we will consider these abilities equitably as we pursue new standards for health care delivery.

Corresponding author: Gregory D. Snyder, MD, MBA, 2014 Washington Street, Newton, MA 02462; [email protected].

Disclosures: None.
 

Equitable Standards for All Patients in a Crisis

Health care delivered during a pandemic instantiates medicine’s perspectives on the value of human life in clinical scenarios where resource allocation is limited. The COVID-19 pandemic has fostered dialogue and debate around the ethical principles that underly such resource allocation, which generally balance (1) utilitarian optimization of resources, (2) equality or equity in health access, (3) the instrumental value of individuals as agents in society, and (4) prioritizing the “worst off” in their natural history of disease.^1,2 State legislatures and health systems have responded to the challeges posed by COVID-19 by considering both the scarcity of intensive care resources, such as mechanical ventilation and hemodialysis, and the clinical criteria to be used for determining which patients should receive said resources. These crisis guidelines have yielded several concerning themes vis-à-vis equitable distribution of health care resources, particularly when the disability status of patients is considered alongside life-expectancy or quality of life.³

Crisis standards of care (CSC) prioritize population-level health under a utilitarian paradigm, explicitly maximizing “life-years” within a population of patients rather than the life of any individual patient.⁴ Debated during initial COVID surges, these CSC guidelines have recently been enacted at the state level in several settings, including Alaska and Idaho.⁵ In a setting with scarce intensive care resources, balancing health equity in access to these resources against population-based survival metrics has been a challenge for commissions considering CSC.^6,7 This need for balance has further promoted systemic views of “disability,” raising concern for structural “ableism” and highlighting the need for greater “ability awareness” in clinicians’ continued professional learning.

Structural Ableism: Defining Perspectives to Address Health Equity

Ableism has been defined as “a system that places value on people’s bodies and minds, based on societally constructed ideas of normalcy, intelligence, excellence, and productivity…[and] leads to people and society determining who is valuable and worthy based on their appearance and/or their ability to satisfactorily [re]produce, excel, and ‘behave.’”⁸ Regarding CSC, concerns about systemic bias in guideline design were raised early by disability advocacy groups during comment periods.^9,10 More broadly, concerns about ableism sit alongside many deeply rooted societal perspectives of disabled individuals as pitiable or, conversely, heroic for having “overcome” their disability in some way. As a physician who sits in a manual wheelchair with paraplegia and mobility impairment, I have equally been subject to inappropriate bias and inappropriate praise for living in a wheelchair. I have also wondered, alongside my patients living with different levels of mobility or ability, why others often view us as “worse off.” Addressing directly whether disabled individuals are “worse off,” disability rights attorney and advocate Harriet McBryde Johnson has articulated a predominant sentiment among persons living with unique or different abilities:

Are we “worse off”? I don’t think so. Not in any meaningful way. There are too many variables. For those of us with congenital conditions, disability shapes all we are. Those disabled later in life adapt. We take constraints that no one would choose and build rich and satisfying lives within them. We enjoy pleasures other people enjoy and pleasures peculiarly our own. We have something the world needs.¹¹

Many physician colleagues have common, invisible diseases such as diabetes and heart disease; fewer colleagues share conditions that are as visible as my spinal cord injury, as readily apparent to patients upon my entry to their hospital rooms. This simultaneous and inescapable identity as both patient and provider has afforded me wonderful doctor-patient interactions, particularly with those patients who appreciate how my patient experience impacts my ability to partially understand theirs. However, this simultaneous identity as doctor and patient also informed my personal and professional concerns regarding structural ableism as I considered scoring my own acutely ill hospital medicine patients with CSC triage scores in April 2020.

As a practicing hospital medicine physician, I have been emboldened by the efforts of my fellow clinicians amid COVID-19; their efforts have reaffirmed all the reasons I pursued a career in medicine. However, when I heard my clinical colleagues’ first explanation of the Massachusetts CSC guidelines in April 2020, I raised my hand to ask whether the “life-years” to which the guidelines referred were quality-adjusted. My concern regarding the implicit use of quality-adjusted life years (QALY) or disability-adjusted life years in clinical decision-making and implementation of these guidelines was validated when no clinical leaders could address this question directly. Sitting on the CSC committee for my hospital during this time was an honor. However, it was disconcerting to hear many clinicians’ unease when estimating mean survival for common chronic diseases, ranging from end-stage renal disease to advanced heart failure. If my expert colleagues, clinical specialists in kidney and heart disease, could not confidently apply mean survival estimates to multimorbid hospital patients, then idiosyncratic clinical judgment was sure to have a heavy hand in any calculation of “life-years.” Thus, my primary concern was that clinicians using triage heuristics would be subject to bias, regardless of their intention, and negatively adjust for the quality of a disabled life in their CSC triage scoring. My secondary concern was that the CSC guidelines themselves included systemic bias against disabled individuals.

According to CSC schema, triage scores index heavily on Sequential Organ Failure Assessment (SOFA) scores to define short-term survival; SOFA scores are partially driven by the Glasgow Coma Scale (GCS). Following professional and public comment periods, CSC guidelines in Massachusetts were revised to, among other critical points of revision, change prognostic estimation via “life years” in favor of generic estimation of short-term survival (Table). I wondered, if I presented to an emergency department with severe COVID-19 and was scored with the GCS for the purpose of making a CSC ventilator triage decision, how would my complete paraplegia and lower-extremity motor impairment be accounted for by a clinician assessing “best motor response” in the GCS? The purpose of these scores is to act algorithmically, to guide clinicians whose cognitive load and time limitations may not allow for adjustment of these algorithms based on the individual patient in front of them. Individualization of clinical decisions is part of medicine’s art, but is difficult in the best of times and no easier during a crisis in care delivery. As CSC triage scores were amended and addended throughout 2020, I returned to the COVID wards, time and again wondering, “What have we learned about systemic bias and health inequity in the CSC process and the pandemic broadly, with specific regard to disability?”

Ability Awareness: Room for Our Improvement

Unfortunately, there is reason to believe that clinical judgment is impaired by structural ableism. In seminal work on this topic, Gerhart et al¹² demonstrated that clinicians considered spinal cord injury (SCI) survivors to have low self-perceptions of worthiness, overall negative attitudes, and low self-esteem as compared to able-bodied individuals. However, surveyed SCI survivors generally had similar self-perceptions of worth and positivity as compared to ”able-bodied” clinicians.¹² For providers who care for persons with disabilities, the majority (82.4%) have rated their disabled patients’ quality of life as worse.¹³ It is no wonder that patients with disabilities are more likely to feel that their doctor-patient relationship is impacted by lack of understanding, negative sentiment, or simple lack of listening.¹⁴ Generally, this poor doctor-patient relationship with disabled patients is exacerbated by poor exposure of medical trainees to disability education; only 34.2% of internal medicine residents recall any form of disability education in medical school, while only 52% of medical school deans report having disability educational content in their curricula.^15,16 There is a similar lack of disability representation in the population of medical trainees themselves. While approximately 20% of the American population lives with a disability, less than 2% of American medical students have a disability.^17-19

While representation of disabled populations in medical practice remains poor, disabled patients are generally less likely to receive age-appropriate prevention, appropriate access to care, and equal access to treatment.^20-22 “Diagnostic overshadowing” refers to clinicians’ attribution of nonspecific signs or symptoms to a patient’s chronic disability as opposed to acute illness.²³ This phenomenon has led to higher rates of preventable malignancy in disabled patients and misattribution of common somatic symptoms to intellectual disability.^24,25 With this disparity in place as status quo for health care delivery to disabled populations, it is no surprise that certain portions of the disabled population have accounted for disproportionate mortality due to COVID-19.^26,27Disability advocates have called for “nothing about us without us,” a phrase associated with the United Nations Convention on the Rights of Persons with Disabilities. Understanding the profound neurodiversity among several forms of sensory and cognitive disabilities, as well as the functional difference between cognitive disabilities, mobility impairment, and inability to meet one’s instrumental activities of daily living independently, others have proposed a unique approach to certain disabled populations in COVID care.²⁸ My own perspective is that definite progress may require a more general understanding of the prevalence of disability by clinicians, both via medical training and by directly addressing health equity for disabled populations in such calculations as the CSC. Systemic ableism is apparent in our most common clinical scoring systems, ranging from the GCS and Functional Assessment Staging Table to the Eastern Cooperative Oncology Group and Karnofsky Performance Status scales. I have reexamined these scoring systems in my own understanding given their general equation of ambulation with ability or normalcy. As a doctor in a manual wheelchair who values greatly my personal quality of life and professional contribution to patient care, I worry that these scoring systems inherently discount my own equitable access to care. Individualization of patients’ particular abilities in the context of these scales must occur alongside evidence-based, guideline-directed management via these scoring systems.

Conclusion: Future Orientation

Updated CSC guidelines have accounted for the unique considerations of disabled patients by effectively caveating their scoring algorithms, directing clinicians via disclaimers to uniquely consider their disabled patients in clinical judgement. This is a first step, but it is also one that erodes the value of algorithms, which generally obviate more deliberative thinking and individualization. For our patients who lack certain abilities, as CSC continue to be activated in several states, we have an opportunity to pursue more inherently equitable solutions before further suffering accrues.²⁹ By way of example, adaptations to scoring systems that leverage QALYs for value-based drug pricing indices have been proposed by organizations like the Institute for Clinical and Economic Review, which proposed the Equal-Value-of Life-Years-Gained framework to inform QALY-based arbitration of drug pricing.³⁰ This is not a perfect rubric but instead represents an attempt to balance consideration of drugs, as has been done with ventilators during the pandemic, as a scare and expensive resource while addressing the just concerns of advocacy groups in structural ableism.

Resource stewardship during a crisis should not discount those states of human life that are perceived to be less desirable, particularly if they are not experienced as less desirable but are experienced uniquely. Instead, we should consider equitably measuring our intervention to match a patient’s needs, as we would dose-adjust a medication for renal function or consider minimally invasive procedures for multimorbid patients. COVID-19 has reflected our profession’s ethical adaptation during crisis as resources have become scarce; there is no better time to define solutions for health equity. We should now be concerned equally by the influence our personal biases have on our clinical practice and by the way in which these crisis standards will influence patients’ perception of and trust in their care providers during periods of perceived plentiful resources in the future. Health care resources are always limited, allocated according to societal values; if we value health equity for people of all abilities, then we will consider these abilities equitably as we pursue new standards for health care delivery.

Corresponding author: Gregory D. Snyder, MD, MBA, 2014 Washington Street, Newton, MA 02462; [email protected].

Disclosures: None.
 

Considering the controversy surrounding functional medicine, you may be wondering why JFP published an article about it last month.¹ David Gorski, MD, PhD, FACS, a vocal critic of functional medicine, commented: “Functional medicine. It sounds so … scientific and reasonable. It’s anything but. In fact, functional medicine combines the worst features of conventional medicine with a heapin’ helpin’ of quackery.”² On its website, however, The Institute for Functional Medicine claims that “functional medicine determines how and why illness occurs and restores health by addressing the root causes of disease for each individual.”³

I suspect the truth lies somewhere in between.

Does functional medicine combine “the worst features of conventional medicine with a heapin’ helpin’ of quackery”? Or is it still in its infancy and does it deserve a wait-and-see approach?

Because functional medicine has gained a certain degree of popularity, I felt it was important for family physicians and other primary care clinicians to know enough about this alternative healing method to discuss it with patients who express interest.

In their review article in JFP, Orlando and colleagues tell us there are 7 defining characteristics of functional medicine.¹ It is patient centered rather than disease centered, uses a “systems biology” approach, considers the dynamic balance of gene-environment interactions, is personalized based on biochemical individuality, promotes organ reserve and sustained health span, sees health as a positive vitality (not merely the absence of disease), and focuses on function rather than pathology.

Most of these statements about functional medicine apply to traditional family medicine. The clinical approach stressing lifestyle changes is mainstream, not unique. The focus on digestion and the microbiome as an important determinant of health is based on interesting basic science studies and associations noted between certain microbiome profiles and diseases.

But association is not causation. So far there is scant evidence that changing the microbiome results in better health, although some preliminary case series have generated intriguing hypotheses. And there is evidence that probiotics improve some symptoms. Ongoing research into the microbiome and health will, no doubt, be illuminating. We have much to learn.

What does seem unique, but suspect, about functional medicine is its focus on biochemical testing of unproven value and the prescribing of diets and supplements based on the test results. There are no sound scientific studies showing the benefit of this approach.

I suggest you read Orlando et al’s article. Functional medicine is an interesting, mostly unproven, approach to patient care. But I will keep an open mind until we see better research that either does—or doesn’t—support the validity of its practices.

Considering the controversy surrounding functional medicine, you may be wondering why JFP published an article about it last month.¹ David Gorski, MD, PhD, FACS, a vocal critic of functional medicine, commented: “Functional medicine. It sounds so … scientific and reasonable. It’s anything but. In fact, functional medicine combines the worst features of conventional medicine with a heapin’ helpin’ of quackery.”² On its website, however, The Institute for Functional Medicine claims that “functional medicine determines how and why illness occurs and restores health by addressing the root causes of disease for each individual.”³

I suspect the truth lies somewhere in between.

Does functional medicine combine “the worst features of conventional medicine with a heapin’ helpin’ of quackery”? Or is it still in its infancy and does it deserve a wait-and-see approach?

Because functional medicine has gained a certain degree of popularity, I felt it was important for family physicians and other primary care clinicians to know enough about this alternative healing method to discuss it with patients who express interest.

In their review article in JFP, Orlando and colleagues tell us there are 7 defining characteristics of functional medicine.¹ It is patient centered rather than disease centered, uses a “systems biology” approach, considers the dynamic balance of gene-environment interactions, is personalized based on biochemical individuality, promotes organ reserve and sustained health span, sees health as a positive vitality (not merely the absence of disease), and focuses on function rather than pathology.

Most of these statements about functional medicine apply to traditional family medicine. The clinical approach stressing lifestyle changes is mainstream, not unique. The focus on digestion and the microbiome as an important determinant of health is based on interesting basic science studies and associations noted between certain microbiome profiles and diseases.

But association is not causation. So far there is scant evidence that changing the microbiome results in better health, although some preliminary case series have generated intriguing hypotheses. And there is evidence that probiotics improve some symptoms. Ongoing research into the microbiome and health will, no doubt, be illuminating. We have much to learn.

What does seem unique, but suspect, about functional medicine is its focus on biochemical testing of unproven value and the prescribing of diets and supplements based on the test results. There are no sound scientific studies showing the benefit of this approach.

I suggest you read Orlando et al’s article. Functional medicine is an interesting, mostly unproven, approach to patient care. But I will keep an open mind until we see better research that either does—or doesn’t—support the validity of its practices.

Considering the controversy surrounding functional medicine, you may be wondering why JFP published an article about it last month.¹ David Gorski, MD, PhD, FACS, a vocal critic of functional medicine, commented: “Functional medicine. It sounds so … scientific and reasonable. It’s anything but. In fact, functional medicine combines the worst features of conventional medicine with a heapin’ helpin’ of quackery.”² On its website, however, The Institute for Functional Medicine claims that “functional medicine determines how and why illness occurs and restores health by addressing the root causes of disease for each individual.”³

I suspect the truth lies somewhere in between.

Does functional medicine combine “the worst features of conventional medicine with a heapin’ helpin’ of quackery”? Or is it still in its infancy and does it deserve a wait-and-see approach?

Because functional medicine has gained a certain degree of popularity, I felt it was important for family physicians and other primary care clinicians to know enough about this alternative healing method to discuss it with patients who express interest.

In their review article in JFP, Orlando and colleagues tell us there are 7 defining characteristics of functional medicine.¹ It is patient centered rather than disease centered, uses a “systems biology” approach, considers the dynamic balance of gene-environment interactions, is personalized based on biochemical individuality, promotes organ reserve and sustained health span, sees health as a positive vitality (not merely the absence of disease), and focuses on function rather than pathology.

Most of these statements about functional medicine apply to traditional family medicine. The clinical approach stressing lifestyle changes is mainstream, not unique. The focus on digestion and the microbiome as an important determinant of health is based on interesting basic science studies and associations noted between certain microbiome profiles and diseases.

But association is not causation. So far there is scant evidence that changing the microbiome results in better health, although some preliminary case series have generated intriguing hypotheses. And there is evidence that probiotics improve some symptoms. Ongoing research into the microbiome and health will, no doubt, be illuminating. We have much to learn.

What does seem unique, but suspect, about functional medicine is its focus on biochemical testing of unproven value and the prescribing of diets and supplements based on the test results. There are no sound scientific studies showing the benefit of this approach.

I suggest you read Orlando et al’s article. Functional medicine is an interesting, mostly unproven, approach to patient care. But I will keep an open mind until we see better research that either does—or doesn’t—support the validity of its practices.

Americans can now have free COVID-19 rapid tests delivered directly to their homes.

The Biden administration’s new no-cost, at-home testing program launched Jan. 18, a day ahead of schedule.

The administration said 500 million tests are available to be delivered to homes across the country. This accounts for half of the president’s recent pledge to purchase 1 billion free at-home COVID-19 tests to distribute to the American public.

On a Jan. 14 call with reporters, senior White House officials offered some details about the new program.

Here’s what we know so far.

How do I order my free tests?

Americans can visit COVIDtests.gov to order their rapid at-home tests. You can also order directly from the U.S. Postal Service website. After you order, you’ll receive a confirmation email that promises to send tracking information once your order ships.

What information do I need to order the tests?

You only need your name and home mailing address.

There is also an option to provide your email address to get updates on the status of your order.

What if someone needs help ordering the tests?

There will be a free call-in line for people needing more help, including those having trouble accessing the internet, according to White House officials.

What tests will be available?

There are nine at-home tests available through FDA emergency use authorization. According to the Frequently Asked Questions section of COVIDtests.gov, "You will not be able to choose the  brand  you order as part of this program.”

How long will it take to get the tests once I order them?

Tests are expected to ship 7 to 12 days after you order them.

But White House officials say that the time frame will likely shorten as the program gains steam.

How many can I order?

There’s a limit of four tests per residential mailing address.

For larger families, White House officials suggest trying other free testing options, like visiting COVID-19 testing sites or your local health center.

Is this a one-time opportunity?

The White House doesn’t say, but officials did mention that if you run out of your four free tests, there are many other ways to access free at-home tests, such as COVID-19 testing sites, pharmacies, and community health centers.

The free tests available through COVIDtests.gov are in addition to an estimated 375 million at-home rapid tests on the market in the U.S. this month.

When should people use a rapid at-home test?

The CDC and experts with other public health groups agree that Americans should consider using at-home rapid tests in the following situations:

• If they begin to have symptoms consistent with COVID-19;
• At least 5 days after close contact with someone who has COVID;
• If someone is indoors with a group of people who are at risk of severe disease or are unvaccinated.

Are at-home rapid tests accurate?

The U.S. Department of Health and Human Services and other federal officials confirmed through studies that all tests distributed through this program can detect the Omicron variant. These agencies also confirmed that their performance is consistent with the FDA’s emergency use authorization.

Is the website designed to handle high demand?

After the original website to sign up for health insurance under the Affordable Care Act crashed repeatedly at launch, the government says it has prepared for high demand for ordering at-home rapid tests.

The U.S. Digital Service (USDS), an organization founded after Healthcare.gov, has partnered with the Postal Service to plan for the launch.

The Postal Service has expanded its staffing, similar to what’s done during the holidays.

All orders in the continental United States will be shipped through first-class mail, with shipments to Alaska, Hawaii, U.S. territories, and military and overseas addresses sent through priority mail.

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

Americans can now have free COVID-19 rapid tests delivered directly to their homes.

The Biden administration’s new no-cost, at-home testing program launched Jan. 18, a day ahead of schedule.

The administration said 500 million tests are available to be delivered to homes across the country. This accounts for half of the president’s recent pledge to purchase 1 billion free at-home COVID-19 tests to distribute to the American public.

On a Jan. 14 call with reporters, senior White House officials offered some details about the new program.

Here’s what we know so far.

How do I order my free tests?

Americans can visit COVIDtests.gov to order their rapid at-home tests. You can also order directly from the U.S. Postal Service website. After you order, you’ll receive a confirmation email that promises to send tracking information once your order ships.

What information do I need to order the tests?

You only need your name and home mailing address.

There is also an option to provide your email address to get updates on the status of your order.

What if someone needs help ordering the tests?

There will be a free call-in line for people needing more help, including those having trouble accessing the internet, according to White House officials.

What tests will be available?

There are nine at-home tests available through FDA emergency use authorization. According to the Frequently Asked Questions section of COVIDtests.gov, "You will not be able to choose the  brand  you order as part of this program.”

How long will it take to get the tests once I order them?

Tests are expected to ship 7 to 12 days after you order them.

But White House officials say that the time frame will likely shorten as the program gains steam.

How many can I order?

There’s a limit of four tests per residential mailing address.

For larger families, White House officials suggest trying other free testing options, like visiting COVID-19 testing sites or your local health center.

Is this a one-time opportunity?

The White House doesn’t say, but officials did mention that if you run out of your four free tests, there are many other ways to access free at-home tests, such as COVID-19 testing sites, pharmacies, and community health centers.

The free tests available through COVIDtests.gov are in addition to an estimated 375 million at-home rapid tests on the market in the U.S. this month.

When should people use a rapid at-home test?

The CDC and experts with other public health groups agree that Americans should consider using at-home rapid tests in the following situations:

• If they begin to have symptoms consistent with COVID-19;
• At least 5 days after close contact with someone who has COVID;
• If someone is indoors with a group of people who are at risk of severe disease or are unvaccinated.

Are at-home rapid tests accurate?

The U.S. Department of Health and Human Services and other federal officials confirmed through studies that all tests distributed through this program can detect the Omicron variant. These agencies also confirmed that their performance is consistent with the FDA’s emergency use authorization.

Is the website designed to handle high demand?

After the original website to sign up for health insurance under the Affordable Care Act crashed repeatedly at launch, the government says it has prepared for high demand for ordering at-home rapid tests.

The U.S. Digital Service (USDS), an organization founded after Healthcare.gov, has partnered with the Postal Service to plan for the launch.

The Postal Service has expanded its staffing, similar to what’s done during the holidays.

All orders in the continental United States will be shipped through first-class mail, with shipments to Alaska, Hawaii, U.S. territories, and military and overseas addresses sent through priority mail.

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

Americans can now have free COVID-19 rapid tests delivered directly to their homes.

The Biden administration’s new no-cost, at-home testing program launched Jan. 18, a day ahead of schedule.

The administration said 500 million tests are available to be delivered to homes across the country. This accounts for half of the president’s recent pledge to purchase 1 billion free at-home COVID-19 tests to distribute to the American public.

On a Jan. 14 call with reporters, senior White House officials offered some details about the new program.

Here’s what we know so far.

How do I order my free tests?

Americans can visit COVIDtests.gov to order their rapid at-home tests. You can also order directly from the U.S. Postal Service website. After you order, you’ll receive a confirmation email that promises to send tracking information once your order ships.

What information do I need to order the tests?

You only need your name and home mailing address.

There is also an option to provide your email address to get updates on the status of your order.

What if someone needs help ordering the tests?

There will be a free call-in line for people needing more help, including those having trouble accessing the internet, according to White House officials.

What tests will be available?

There are nine at-home tests available through FDA emergency use authorization. According to the Frequently Asked Questions section of COVIDtests.gov, "You will not be able to choose the  brand  you order as part of this program.”

How long will it take to get the tests once I order them?

Tests are expected to ship 7 to 12 days after you order them.

But White House officials say that the time frame will likely shorten as the program gains steam.

How many can I order?

There’s a limit of four tests per residential mailing address.

For larger families, White House officials suggest trying other free testing options, like visiting COVID-19 testing sites or your local health center.

Is this a one-time opportunity?

The White House doesn’t say, but officials did mention that if you run out of your four free tests, there are many other ways to access free at-home tests, such as COVID-19 testing sites, pharmacies, and community health centers.

The free tests available through COVIDtests.gov are in addition to an estimated 375 million at-home rapid tests on the market in the U.S. this month.

When should people use a rapid at-home test?

The CDC and experts with other public health groups agree that Americans should consider using at-home rapid tests in the following situations:

• If they begin to have symptoms consistent with COVID-19;
• At least 5 days after close contact with someone who has COVID;
• If someone is indoors with a group of people who are at risk of severe disease or are unvaccinated.

Are at-home rapid tests accurate?

The U.S. Department of Health and Human Services and other federal officials confirmed through studies that all tests distributed through this program can detect the Omicron variant. These agencies also confirmed that their performance is consistent with the FDA’s emergency use authorization.

Is the website designed to handle high demand?

After the original website to sign up for health insurance under the Affordable Care Act crashed repeatedly at launch, the government says it has prepared for high demand for ordering at-home rapid tests.

The U.S. Digital Service (USDS), an organization founded after Healthcare.gov, has partnered with the Postal Service to plan for the launch.

The Postal Service has expanded its staffing, similar to what’s done during the holidays.

All orders in the continental United States will be shipped through first-class mail, with shipments to Alaska, Hawaii, U.S. territories, and military and overseas addresses sent through priority mail.

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

Fed up with personal attacks on the nation’s top infectious disease expert, scores of leading scientists and physicians have signed an open letter defending Anthony Fauci, MD, for his years of service to the public and his leadership on the pandemic.

“We deplore the personal attacks on Dr. Fauci. The criticism is inaccurate, unscientific, ill-founded in the facts and, increasingly, motivated by partisan politics,” reads the letter of support, initiated by Ezekiel Emanuel, MD, and signed by almost 300 scientists and public health and medical professionals, including Nobel Laureates, a former Republican senator, and leadership of medical societies and institutions.

Dr. Fauci has led the National Institute for Allergy and Infectious Diseases since 1984 and serves as President Biden’s top medical advisor on the pandemic.

“Dr. Anthony Fauci has served the U.S.A. with wisdom and integrity for nearly 40 years. Through HIV, Ebola, and now COVID, he has unswervingly served the United States guiding the country to very successful outcomes. He has our unreserved respect and trust as a scientist and a national leader,” the letter reads.

Dr. Fauci has repeatedly faced harsh criticism from congressional Republicans, especially Sen. Rand Paul (R-Ky.) and Sen. Roger Marshall (R-Kan.).

At a particularly contentious congressional hearing earlier this week on the federal government’s response to Omicron, Dr. Fauci fought back, telling Sen. Marshall, “You’re so misinformed, it’s extraordinary.”

Dr. Fauci, who has received death threats and harassment of his family, told Sen. Rand that his “completely untrue” statements and rhetoric “kindles the crazies out there.”
 

‘Sagacious counsel’

The personal attacks on Dr. Fauci are a “distraction from what should be the national focus – working together to finally overcome a pandemic that is killing about 500,000 people a year. We are grateful for Dr. Fauci’s dedication and tireless efforts to help the country through this pandemic and other health crises,” the letter reads.

“Throughout the COVID-19 pandemic, Dr. Fauci has provided the American political leadership and the public with sagacious counsel in these most difficult of times. His advice has been as well informed as data and the rapidly evolving circumstances allowed,” it states.

“Importantly,” Dr. Fauci has given his advice with “humility, being clear about what we know and what is unknown, but requires judgment. He has consistently emphasized the importance of mask-wearing, social distancing, and vaccination. These are standard and necessary public health measures that we all support,” the letter states.

“We are grateful that Dr. Fauci has consistently stated the science in a way that represents the facts as they emerge, without unwarranted speculation.”

“Sadly, in these politically polarized times where misinformation contaminates the United States’ response to the pandemic, routine public health measures have become unnecessarily controversial, undermining the effectiveness of our country’s response,” the letter reads.

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

Fed up with personal attacks on the nation’s top infectious disease expert, scores of leading scientists and physicians have signed an open letter defending Anthony Fauci, MD, for his years of service to the public and his leadership on the pandemic.

“We deplore the personal attacks on Dr. Fauci. The criticism is inaccurate, unscientific, ill-founded in the facts and, increasingly, motivated by partisan politics,” reads the letter of support, initiated by Ezekiel Emanuel, MD, and signed by almost 300 scientists and public health and medical professionals, including Nobel Laureates, a former Republican senator, and leadership of medical societies and institutions.

Dr. Fauci has led the National Institute for Allergy and Infectious Diseases since 1984 and serves as President Biden’s top medical advisor on the pandemic.

“Dr. Anthony Fauci has served the U.S.A. with wisdom and integrity for nearly 40 years. Through HIV, Ebola, and now COVID, he has unswervingly served the United States guiding the country to very successful outcomes. He has our unreserved respect and trust as a scientist and a national leader,” the letter reads.

Dr. Fauci has repeatedly faced harsh criticism from congressional Republicans, especially Sen. Rand Paul (R-Ky.) and Sen. Roger Marshall (R-Kan.).

At a particularly contentious congressional hearing earlier this week on the federal government’s response to Omicron, Dr. Fauci fought back, telling Sen. Marshall, “You’re so misinformed, it’s extraordinary.”

Dr. Fauci, who has received death threats and harassment of his family, told Sen. Rand that his “completely untrue” statements and rhetoric “kindles the crazies out there.”
 

‘Sagacious counsel’

The personal attacks on Dr. Fauci are a “distraction from what should be the national focus – working together to finally overcome a pandemic that is killing about 500,000 people a year. We are grateful for Dr. Fauci’s dedication and tireless efforts to help the country through this pandemic and other health crises,” the letter reads.

“Throughout the COVID-19 pandemic, Dr. Fauci has provided the American political leadership and the public with sagacious counsel in these most difficult of times. His advice has been as well informed as data and the rapidly evolving circumstances allowed,” it states.

“Importantly,” Dr. Fauci has given his advice with “humility, being clear about what we know and what is unknown, but requires judgment. He has consistently emphasized the importance of mask-wearing, social distancing, and vaccination. These are standard and necessary public health measures that we all support,” the letter states.

“We are grateful that Dr. Fauci has consistently stated the science in a way that represents the facts as they emerge, without unwarranted speculation.”

“Sadly, in these politically polarized times where misinformation contaminates the United States’ response to the pandemic, routine public health measures have become unnecessarily controversial, undermining the effectiveness of our country’s response,” the letter reads.

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

Fed up with personal attacks on the nation’s top infectious disease expert, scores of leading scientists and physicians have signed an open letter defending Anthony Fauci, MD, for his years of service to the public and his leadership on the pandemic.

“We deplore the personal attacks on Dr. Fauci. The criticism is inaccurate, unscientific, ill-founded in the facts and, increasingly, motivated by partisan politics,” reads the letter of support, initiated by Ezekiel Emanuel, MD, and signed by almost 300 scientists and public health and medical professionals, including Nobel Laureates, a former Republican senator, and leadership of medical societies and institutions.

Dr. Fauci has led the National Institute for Allergy and Infectious Diseases since 1984 and serves as President Biden’s top medical advisor on the pandemic.

“Dr. Anthony Fauci has served the U.S.A. with wisdom and integrity for nearly 40 years. Through HIV, Ebola, and now COVID, he has unswervingly served the United States guiding the country to very successful outcomes. He has our unreserved respect and trust as a scientist and a national leader,” the letter reads.

Dr. Fauci has repeatedly faced harsh criticism from congressional Republicans, especially Sen. Rand Paul (R-Ky.) and Sen. Roger Marshall (R-Kan.).

At a particularly contentious congressional hearing earlier this week on the federal government’s response to Omicron, Dr. Fauci fought back, telling Sen. Marshall, “You’re so misinformed, it’s extraordinary.”

Dr. Fauci, who has received death threats and harassment of his family, told Sen. Rand that his “completely untrue” statements and rhetoric “kindles the crazies out there.”
 

‘Sagacious counsel’

The personal attacks on Dr. Fauci are a “distraction from what should be the national focus – working together to finally overcome a pandemic that is killing about 500,000 people a year. We are grateful for Dr. Fauci’s dedication and tireless efforts to help the country through this pandemic and other health crises,” the letter reads.

“Throughout the COVID-19 pandemic, Dr. Fauci has provided the American political leadership and the public with sagacious counsel in these most difficult of times. His advice has been as well informed as data and the rapidly evolving circumstances allowed,” it states.

“Importantly,” Dr. Fauci has given his advice with “humility, being clear about what we know and what is unknown, but requires judgment. He has consistently emphasized the importance of mask-wearing, social distancing, and vaccination. These are standard and necessary public health measures that we all support,” the letter states.

“We are grateful that Dr. Fauci has consistently stated the science in a way that represents the facts as they emerge, without unwarranted speculation.”

“Sadly, in these politically polarized times where misinformation contaminates the United States’ response to the pandemic, routine public health measures have become unnecessarily controversial, undermining the effectiveness of our country’s response,” the letter reads.

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

The CDC is preparing to update its COVID-19 mask recommendations to emphasize the use of N95 and KN95 masks that better filter the virus, Director Rochelle Walensky, MD, said on Jan. 12.

“We are preparing an update to the info on our mask website to best reflect the options that are available to people and the different levels of protection different masks provide, and we want to provide Americans the best and most updated information to choose what mask is going to be right for them,” she said at a White House news briefing.

While the higher-quality masks provide better protection, they can be uncomfortable to wear, expensive, and harder to find. That’s why Dr. Walensky added an important caveat.

“Any mask is better than no mask, and we do encourage all Americans to wear a well-fitting mask to protect themselves and prevent the spread of COVID-19. That recommendation is not going to change,” she said.

“Most importantly, the best mask that you wear is the one you will wear and the one you can keep on all day long and tolerate in public indoor settings.”

Meanwhile, the World Health Organization was more focused on vaccines.

WHO officials stressed on Jan. 12 that global vaccine distribution is first priority in defeating the highly contagious Omicron variant, as well as other variants that may evolve. 

The WHO’s Technical Advisory Group on COVID-19 Vaccine Composition – a group of experts assessing how COVID-19 vaccines perform against Omicron and other emerging variants – says there is an “urgent need” for broader access to vaccines, along with reviewing and updating current vaccines as needed to ensure protection. 

The WHO also disputed the idea that COVID-19 could become endemic in one largely vaccinated nation, while the rest of the world remains unprotected. 

“It is up to us how this pandemic unfolds,” Maria Van Kerkhove, PhD, the WHO’s technical lead on COVID-19 response, said at a news briefing. 

The WHO has a goal of vaccinating 70% of the population of every country by the middle of the year.

But right now, 90 countries have yet to reach 40% vaccination rates, and 36 of those countries have less than 10% of their populations vaccinated, according to WHO Director General Tedros Adhanom Ghebreyesus, PhD.

A staggering 85% of the African population has not received a first dose.

But progress is being made, Dr. Ghebreyesus said at the briefing. 

The WHO said there were over 15 million COVID-19 cases reported last week – the most ever in a single week – and this is likely an underestimate. 

The Omicron variant, first identified in South Africa 2 months ago and now found on all seven continents, is “rapidly replacing Delta in almost all countries,” Dr. Ghebreyesus said.

Dr. Walensky said this week’s U.S. daily average COVID-19 case count was 751,000, an increase of 47% from last week. The average daily hospital admissions this week is 19,800, an increase of 33%. Deaths are up 40%, reaching 1,600 per day.

But she also reported new data that supports other research showing Omicron may produce less severe disease. Kaiser Permanente Southern California released a study on Jan. 11 showing that, compared with Delta infections, Omicron was associated with a 53% reduction in hospitalizations, a 74% reduction in intensive care unit admissions, and a 91% lower risk of death.

In the study, no patients with Omicron required mechanical ventilation. The strain now accounts for 98% of cases nationwide.

But Dr. Walensky warned the lower disease severity is not enough to make up for the sheer number of cases that continue to overwhelm hospital systems.

“While we are seeing early evidence that Omicron is less severe than Delta and that those infected are less likely to require hospitalization, it’s important to note that Omicron continues to be much more transmissible than Delta,” she said. “The sudden rise in cases due to Omicron is resulting in unprecedented daily case counts, sickness, absenteeism, and strains on our health care system.”

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

The CDC is preparing to update its COVID-19 mask recommendations to emphasize the use of N95 and KN95 masks that better filter the virus, Director Rochelle Walensky, MD, said on Jan. 12.

“We are preparing an update to the info on our mask website to best reflect the options that are available to people and the different levels of protection different masks provide, and we want to provide Americans the best and most updated information to choose what mask is going to be right for them,” she said at a White House news briefing.

While the higher-quality masks provide better protection, they can be uncomfortable to wear, expensive, and harder to find. That’s why Dr. Walensky added an important caveat.

“Any mask is better than no mask, and we do encourage all Americans to wear a well-fitting mask to protect themselves and prevent the spread of COVID-19. That recommendation is not going to change,” she said.

“Most importantly, the best mask that you wear is the one you will wear and the one you can keep on all day long and tolerate in public indoor settings.”

Meanwhile, the World Health Organization was more focused on vaccines.

WHO officials stressed on Jan. 12 that global vaccine distribution is first priority in defeating the highly contagious Omicron variant, as well as other variants that may evolve. 

The WHO’s Technical Advisory Group on COVID-19 Vaccine Composition – a group of experts assessing how COVID-19 vaccines perform against Omicron and other emerging variants – says there is an “urgent need” for broader access to vaccines, along with reviewing and updating current vaccines as needed to ensure protection. 

The WHO also disputed the idea that COVID-19 could become endemic in one largely vaccinated nation, while the rest of the world remains unprotected. 

“It is up to us how this pandemic unfolds,” Maria Van Kerkhove, PhD, the WHO’s technical lead on COVID-19 response, said at a news briefing. 

The WHO has a goal of vaccinating 70% of the population of every country by the middle of the year.

But right now, 90 countries have yet to reach 40% vaccination rates, and 36 of those countries have less than 10% of their populations vaccinated, according to WHO Director General Tedros Adhanom Ghebreyesus, PhD.

A staggering 85% of the African population has not received a first dose.

But progress is being made, Dr. Ghebreyesus said at the briefing. 

The WHO said there were over 15 million COVID-19 cases reported last week – the most ever in a single week – and this is likely an underestimate. 

The Omicron variant, first identified in South Africa 2 months ago and now found on all seven continents, is “rapidly replacing Delta in almost all countries,” Dr. Ghebreyesus said.

Dr. Walensky said this week’s U.S. daily average COVID-19 case count was 751,000, an increase of 47% from last week. The average daily hospital admissions this week is 19,800, an increase of 33%. Deaths are up 40%, reaching 1,600 per day.

But she also reported new data that supports other research showing Omicron may produce less severe disease. Kaiser Permanente Southern California released a study on Jan. 11 showing that, compared with Delta infections, Omicron was associated with a 53% reduction in hospitalizations, a 74% reduction in intensive care unit admissions, and a 91% lower risk of death.

In the study, no patients with Omicron required mechanical ventilation. The strain now accounts for 98% of cases nationwide.

But Dr. Walensky warned the lower disease severity is not enough to make up for the sheer number of cases that continue to overwhelm hospital systems.

“While we are seeing early evidence that Omicron is less severe than Delta and that those infected are less likely to require hospitalization, it’s important to note that Omicron continues to be much more transmissible than Delta,” she said. “The sudden rise in cases due to Omicron is resulting in unprecedented daily case counts, sickness, absenteeism, and strains on our health care system.”

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

The CDC is preparing to update its COVID-19 mask recommendations to emphasize the use of N95 and KN95 masks that better filter the virus, Director Rochelle Walensky, MD, said on Jan. 12.

“We are preparing an update to the info on our mask website to best reflect the options that are available to people and the different levels of protection different masks provide, and we want to provide Americans the best and most updated information to choose what mask is going to be right for them,” she said at a White House news briefing.

While the higher-quality masks provide better protection, they can be uncomfortable to wear, expensive, and harder to find. That’s why Dr. Walensky added an important caveat.

“Any mask is better than no mask, and we do encourage all Americans to wear a well-fitting mask to protect themselves and prevent the spread of COVID-19. That recommendation is not going to change,” she said.

“Most importantly, the best mask that you wear is the one you will wear and the one you can keep on all day long and tolerate in public indoor settings.”

Meanwhile, the World Health Organization was more focused on vaccines.

WHO officials stressed on Jan. 12 that global vaccine distribution is first priority in defeating the highly contagious Omicron variant, as well as other variants that may evolve. 

The WHO’s Technical Advisory Group on COVID-19 Vaccine Composition – a group of experts assessing how COVID-19 vaccines perform against Omicron and other emerging variants – says there is an “urgent need” for broader access to vaccines, along with reviewing and updating current vaccines as needed to ensure protection. 

The WHO also disputed the idea that COVID-19 could become endemic in one largely vaccinated nation, while the rest of the world remains unprotected. 

“It is up to us how this pandemic unfolds,” Maria Van Kerkhove, PhD, the WHO’s technical lead on COVID-19 response, said at a news briefing. 

The WHO has a goal of vaccinating 70% of the population of every country by the middle of the year.

But right now, 90 countries have yet to reach 40% vaccination rates, and 36 of those countries have less than 10% of their populations vaccinated, according to WHO Director General Tedros Adhanom Ghebreyesus, PhD.

A staggering 85% of the African population has not received a first dose.

But progress is being made, Dr. Ghebreyesus said at the briefing. 

The WHO said there were over 15 million COVID-19 cases reported last week – the most ever in a single week – and this is likely an underestimate. 

The Omicron variant, first identified in South Africa 2 months ago and now found on all seven continents, is “rapidly replacing Delta in almost all countries,” Dr. Ghebreyesus said.

Dr. Walensky said this week’s U.S. daily average COVID-19 case count was 751,000, an increase of 47% from last week. The average daily hospital admissions this week is 19,800, an increase of 33%. Deaths are up 40%, reaching 1,600 per day.

But she also reported new data that supports other research showing Omicron may produce less severe disease. Kaiser Permanente Southern California released a study on Jan. 11 showing that, compared with Delta infections, Omicron was associated with a 53% reduction in hospitalizations, a 74% reduction in intensive care unit admissions, and a 91% lower risk of death.

In the study, no patients with Omicron required mechanical ventilation. The strain now accounts for 98% of cases nationwide.

But Dr. Walensky warned the lower disease severity is not enough to make up for the sheer number of cases that continue to overwhelm hospital systems.

“While we are seeing early evidence that Omicron is less severe than Delta and that those infected are less likely to require hospitalization, it’s important to note that Omicron continues to be much more transmissible than Delta,” she said. “The sudden rise in cases due to Omicron is resulting in unprecedented daily case counts, sickness, absenteeism, and strains on our health care system.”

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

The Centers for Disease Control and Prevention’s recently updated guidance on isolating and testing were tied to the public’s increased interest in testing, Director Rochelle Walenksy, MD, said during a White House briefing Jan. 5.

Health officials recently shortened the recommended COVID-19 isolation and quarantine period from 10 days to 5, creating confusion amid an outbreak of the highly transmissible Omicron variant, which now accounts for 95% of cases in the United States.

Then, in slightly updated guidance, the CDC recommended using an at-home antigen test after 5 days of isolation if possible, even though these tests having aren’t as sensitive to the Omicron variant, according to the FDA.

“After we released our recs early last week, it became very clear people were interested in using the rapid test, though not authorized for this purpose after the end of their isolation period,” Dr. Walensky said. “We then provided guidance on how they should be used.”

“If that test is negative, people really do need to understand they must continue to wear their mask for those 5 days,” Dr. Walensky said.

But for many, the CDC guidelines are murky and seem to always change.

“Nearly 2 years into this pandemic, with Omicron cases surging across the country, the American people should be able to count on the Centers for Disease Control and Prevention for timely, accurate, clear guidance to protect themselves, their loved ones, and their communities,” American Medical Association president Gerald Harmon, MD, said in a statement. “Instead, the new recommendations on quarantine and isolation are not only confusing, but are risking further spread of the virus.”

About 31% of people remain infectious 5 days after a positive COVID-19 test, Dr. Harmon said, quoting the CDC’s own rationale for changing its guidance.

“With hundreds of thousands of new cases daily and more than a million positive reported cases on January 3, tens of thousands – potentially hundreds of thousands of people – could return to work and school infectious if they follow the CDC’s new guidance on ending isolation after 5 days without a negative test,” he said. “Physicians are concerned that these recommendations put our patients at risk and could further overwhelm our health care system.”

Instead, Dr. Harmon said a negative test should be required for ending isolation.

“Reemerging without knowing one’s status unnecessarily risks further transmission of the virus,” he said.

Meanwhile, also during the White House briefing, officials said that early data continue to show that Omicron infections are less severe than those from other variants, but skyrocketing cases will still put a strain on the health care system.

“The big caveat is we should not be complacent,” presidential Chief Medical Adviser Anthony Fauci, MD, said a White House briefing Jan. 5.

He added that Omicron “could still stress our hospital system because a certain proportion of a large volume of cases, no matter what, are going to be severe.”

Cases continue to increase greatly. This week’s 7-day daily average of infections is 491,700 -- an increase of 98% over last week, Dr. Walensky said. Hospitalizations, while lagging behind case numbers, are still rising significantly: The daily average is 14,800 admissions, up 63% from last week. Daily deaths this week are 1,200, an increase of only 5%.

Dr. Walensky continues to encourage vaccinations, boosters, and other precautions.

“Vaccines and boosters are protecting people from the severe and tragic outcomes that can occur from COVID-19 infection,” she said. “Get vaccinated and get boosted if eligible, wear a mask, stay home when you’re sick, and take a test if you have symptoms or are looking for greater reassurance before you gather with others.”

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

The Centers for Disease Control and Prevention’s recently updated guidance on isolating and testing were tied to the public’s increased interest in testing, Director Rochelle Walenksy, MD, said during a White House briefing Jan. 5.

Health officials recently shortened the recommended COVID-19 isolation and quarantine period from 10 days to 5, creating confusion amid an outbreak of the highly transmissible Omicron variant, which now accounts for 95% of cases in the United States.

Then, in slightly updated guidance, the CDC recommended using an at-home antigen test after 5 days of isolation if possible, even though these tests having aren’t as sensitive to the Omicron variant, according to the FDA.

“After we released our recs early last week, it became very clear people were interested in using the rapid test, though not authorized for this purpose after the end of their isolation period,” Dr. Walensky said. “We then provided guidance on how they should be used.”

“If that test is negative, people really do need to understand they must continue to wear their mask for those 5 days,” Dr. Walensky said.

But for many, the CDC guidelines are murky and seem to always change.

“Nearly 2 years into this pandemic, with Omicron cases surging across the country, the American people should be able to count on the Centers for Disease Control and Prevention for timely, accurate, clear guidance to protect themselves, their loved ones, and their communities,” American Medical Association president Gerald Harmon, MD, said in a statement. “Instead, the new recommendations on quarantine and isolation are not only confusing, but are risking further spread of the virus.”

About 31% of people remain infectious 5 days after a positive COVID-19 test, Dr. Harmon said, quoting the CDC’s own rationale for changing its guidance.

“With hundreds of thousands of new cases daily and more than a million positive reported cases on January 3, tens of thousands – potentially hundreds of thousands of people – could return to work and school infectious if they follow the CDC’s new guidance on ending isolation after 5 days without a negative test,” he said. “Physicians are concerned that these recommendations put our patients at risk and could further overwhelm our health care system.”

Instead, Dr. Harmon said a negative test should be required for ending isolation.

“Reemerging without knowing one’s status unnecessarily risks further transmission of the virus,” he said.

Meanwhile, also during the White House briefing, officials said that early data continue to show that Omicron infections are less severe than those from other variants, but skyrocketing cases will still put a strain on the health care system.

“The big caveat is we should not be complacent,” presidential Chief Medical Adviser Anthony Fauci, MD, said a White House briefing Jan. 5.

He added that Omicron “could still stress our hospital system because a certain proportion of a large volume of cases, no matter what, are going to be severe.”

Cases continue to increase greatly. This week’s 7-day daily average of infections is 491,700 -- an increase of 98% over last week, Dr. Walensky said. Hospitalizations, while lagging behind case numbers, are still rising significantly: The daily average is 14,800 admissions, up 63% from last week. Daily deaths this week are 1,200, an increase of only 5%.

Dr. Walensky continues to encourage vaccinations, boosters, and other precautions.

“Vaccines and boosters are protecting people from the severe and tragic outcomes that can occur from COVID-19 infection,” she said. “Get vaccinated and get boosted if eligible, wear a mask, stay home when you’re sick, and take a test if you have symptoms or are looking for greater reassurance before you gather with others.”

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

The Centers for Disease Control and Prevention’s recently updated guidance on isolating and testing were tied to the public’s increased interest in testing, Director Rochelle Walenksy, MD, said during a White House briefing Jan. 5.

Health officials recently shortened the recommended COVID-19 isolation and quarantine period from 10 days to 5, creating confusion amid an outbreak of the highly transmissible Omicron variant, which now accounts for 95% of cases in the United States.

Then, in slightly updated guidance, the CDC recommended using an at-home antigen test after 5 days of isolation if possible, even though these tests having aren’t as sensitive to the Omicron variant, according to the FDA.

“After we released our recs early last week, it became very clear people were interested in using the rapid test, though not authorized for this purpose after the end of their isolation period,” Dr. Walensky said. “We then provided guidance on how they should be used.”

“If that test is negative, people really do need to understand they must continue to wear their mask for those 5 days,” Dr. Walensky said.

But for many, the CDC guidelines are murky and seem to always change.

“Nearly 2 years into this pandemic, with Omicron cases surging across the country, the American people should be able to count on the Centers for Disease Control and Prevention for timely, accurate, clear guidance to protect themselves, their loved ones, and their communities,” American Medical Association president Gerald Harmon, MD, said in a statement. “Instead, the new recommendations on quarantine and isolation are not only confusing, but are risking further spread of the virus.”

About 31% of people remain infectious 5 days after a positive COVID-19 test, Dr. Harmon said, quoting the CDC’s own rationale for changing its guidance.

“With hundreds of thousands of new cases daily and more than a million positive reported cases on January 3, tens of thousands – potentially hundreds of thousands of people – could return to work and school infectious if they follow the CDC’s new guidance on ending isolation after 5 days without a negative test,” he said. “Physicians are concerned that these recommendations put our patients at risk and could further overwhelm our health care system.”

Instead, Dr. Harmon said a negative test should be required for ending isolation.

“Reemerging without knowing one’s status unnecessarily risks further transmission of the virus,” he said.

Meanwhile, also during the White House briefing, officials said that early data continue to show that Omicron infections are less severe than those from other variants, but skyrocketing cases will still put a strain on the health care system.

“The big caveat is we should not be complacent,” presidential Chief Medical Adviser Anthony Fauci, MD, said a White House briefing Jan. 5.

He added that Omicron “could still stress our hospital system because a certain proportion of a large volume of cases, no matter what, are going to be severe.”

Cases continue to increase greatly. This week’s 7-day daily average of infections is 491,700 -- an increase of 98% over last week, Dr. Walensky said. Hospitalizations, while lagging behind case numbers, are still rising significantly: The daily average is 14,800 admissions, up 63% from last week. Daily deaths this week are 1,200, an increase of only 5%.

Dr. Walensky continues to encourage vaccinations, boosters, and other precautions.

“Vaccines and boosters are protecting people from the severe and tragic outcomes that can occur from COVID-19 infection,” she said. “Get vaccinated and get boosted if eligible, wear a mask, stay home when you’re sick, and take a test if you have symptoms or are looking for greater reassurance before you gather with others.”

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

The Food and Drug Administration on Jan. 3 authorized the first COVID-19 vaccine booster dose for American adolescents ages 12 to 15.

Besides updating the authorization for the Pfizer COVID-19 vaccine, the agency also shortened the recommended time between a second dose and the booster to 5 months or more, based on new evidence. In addition, a third primary series dose is now authorized for certain immunocompromised children 5 years to 11 years old. Full details are available in an FDA news release.

The amended emergency use authorization (EUA) only applies to the Pfizer vaccine, said acting FDA Commissioner Janet Woodcock, MD.

“Just to make sure every everyone is clear on this, right now: If you got [Johnson & Johnson’s one-dose vaccine], you get a booster after 2 months. If you got Moderna, you can get a booster at 6 months or beyond,” she said during a media briefing.

What is new, she said, is “if you got Pfizer as your primary series, you can get a booster at 5 months or beyond.”
 

A lower risk of myocarditis?

Asked about concerns about the risk of myocarditis with vaccination in the 12- to 15-year age group, Dr. Woodcock said they expect it would be “extremely rare with the third dose.”

“We have the real-world evidence from the Israeli experience to help us with that analysis,” she said.

The data so far consistently points to a higher risk of myocarditis after a second mRNA vaccine dose among males, from teenagers to 30-year-olds, with a peak at about 16 to 17 years of age, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said during the media call.

The risk of myocarditis is about 2 to 3 times higher after a second vaccine dose, compared to a booster shot, Dr. Marks said, based on available data. It may be related to the closer dose timing of the second dose versus a third, he added.

“The inference here is that on the risk of myocarditis with third doses in the 12- to 15-year age range is likely to be quite acceptable,” he said.

Dr. Marks also pointed out that most cases of myocarditis clear up quickly.

“We’re not seeing long-lasting effects. That’s not to say that we don’t care about this and that it’s not important,” he said.

“But what it is saying is that in the setting of a tremendous number of Omicron and Delta cases in this country, the potential benefits of getting vaccinated in this age group outweigh that risk,” Dr. Marks said. “We can look at that risk-benefit and still feel comfortable.”

He said that “the really overwhelming majority of these cases, 98%, have been mild” -- shown by a 1-day median hospital stay.

Even so, the FDA plans to continue monitoring for the risk of myocarditis “very closely,” he said.

Interestingly, swollen underarm lymph nodes were seen more frequently after the booster dose than after the second dose of a two-dose primary series, the FDA said.

Reducing the time between primary vaccination with the Pfizer vaccine -- two initial doses -- and the booster shot from 6 months to 5 months is based on decreasing efficacy data that the drugmaker submitted to the FDA.

The 5-month interval was evaluated in a study from Israel published Dec. 21 in the New England Journal of Medicine .
 

Mixing and matching vaccines

Less clear at the moment is guidance about boosters for people who opted to mix and match their primary vaccine series.

“There was a mix-and-match study that was done which showed that in some cases, the mixing and matching … of an adenoviral record vaccine and an mRNA vaccine seem to give a very good immune response,” Dr. Marks said.

Once more data comes in on mixing and matching, “we’ll analyze them and then potentially make recommendations,” he said.
 

‘It’s not too late’

No federal government media briefing on COVID-19 would be complete without a plea for the unvaccinated to get immunized.

“We’re talking a lot about boosters right now, but it’s not too late for those who have not gotten a vaccine to get a vaccine,” Dr. Marks said, referring to the tens of millions of Americans who remain unvaccinated at the beginning of 2022.

“We know from our previous studies that even a single dose of the vaccine -- and probably two doses -- can help prevent the worst outcomes from COVID-19, including hospitalization and death.”

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

The Food and Drug Administration on Jan. 3 authorized the first COVID-19 vaccine booster dose for American adolescents ages 12 to 15.

Besides updating the authorization for the Pfizer COVID-19 vaccine, the agency also shortened the recommended time between a second dose and the booster to 5 months or more, based on new evidence. In addition, a third primary series dose is now authorized for certain immunocompromised children 5 years to 11 years old. Full details are available in an FDA news release.

The amended emergency use authorization (EUA) only applies to the Pfizer vaccine, said acting FDA Commissioner Janet Woodcock, MD.

“Just to make sure every everyone is clear on this, right now: If you got [Johnson & Johnson’s one-dose vaccine], you get a booster after 2 months. If you got Moderna, you can get a booster at 6 months or beyond,” she said during a media briefing.

What is new, she said, is “if you got Pfizer as your primary series, you can get a booster at 5 months or beyond.”
 

A lower risk of myocarditis?

Asked about concerns about the risk of myocarditis with vaccination in the 12- to 15-year age group, Dr. Woodcock said they expect it would be “extremely rare with the third dose.”

“We have the real-world evidence from the Israeli experience to help us with that analysis,” she said.

The data so far consistently points to a higher risk of myocarditis after a second mRNA vaccine dose among males, from teenagers to 30-year-olds, with a peak at about 16 to 17 years of age, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said during the media call.

The risk of myocarditis is about 2 to 3 times higher after a second vaccine dose, compared to a booster shot, Dr. Marks said, based on available data. It may be related to the closer dose timing of the second dose versus a third, he added.

“The inference here is that on the risk of myocarditis with third doses in the 12- to 15-year age range is likely to be quite acceptable,” he said.

Dr. Marks also pointed out that most cases of myocarditis clear up quickly.

“We’re not seeing long-lasting effects. That’s not to say that we don’t care about this and that it’s not important,” he said.

“But what it is saying is that in the setting of a tremendous number of Omicron and Delta cases in this country, the potential benefits of getting vaccinated in this age group outweigh that risk,” Dr. Marks said. “We can look at that risk-benefit and still feel comfortable.”

He said that “the really overwhelming majority of these cases, 98%, have been mild” -- shown by a 1-day median hospital stay.

Even so, the FDA plans to continue monitoring for the risk of myocarditis “very closely,” he said.

Interestingly, swollen underarm lymph nodes were seen more frequently after the booster dose than after the second dose of a two-dose primary series, the FDA said.

Reducing the time between primary vaccination with the Pfizer vaccine -- two initial doses -- and the booster shot from 6 months to 5 months is based on decreasing efficacy data that the drugmaker submitted to the FDA.

The 5-month interval was evaluated in a study from Israel published Dec. 21 in the New England Journal of Medicine .
 

Mixing and matching vaccines

Less clear at the moment is guidance about boosters for people who opted to mix and match their primary vaccine series.

“There was a mix-and-match study that was done which showed that in some cases, the mixing and matching … of an adenoviral record vaccine and an mRNA vaccine seem to give a very good immune response,” Dr. Marks said.

Once more data comes in on mixing and matching, “we’ll analyze them and then potentially make recommendations,” he said.
 

‘It’s not too late’

No federal government media briefing on COVID-19 would be complete without a plea for the unvaccinated to get immunized.

“We’re talking a lot about boosters right now, but it’s not too late for those who have not gotten a vaccine to get a vaccine,” Dr. Marks said, referring to the tens of millions of Americans who remain unvaccinated at the beginning of 2022.

“We know from our previous studies that even a single dose of the vaccine -- and probably two doses -- can help prevent the worst outcomes from COVID-19, including hospitalization and death.”

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

The Food and Drug Administration on Jan. 3 authorized the first COVID-19 vaccine booster dose for American adolescents ages 12 to 15.

Besides updating the authorization for the Pfizer COVID-19 vaccine, the agency also shortened the recommended time between a second dose and the booster to 5 months or more, based on new evidence. In addition, a third primary series dose is now authorized for certain immunocompromised children 5 years to 11 years old. Full details are available in an FDA news release.

The amended emergency use authorization (EUA) only applies to the Pfizer vaccine, said acting FDA Commissioner Janet Woodcock, MD.

“Just to make sure every everyone is clear on this, right now: If you got [Johnson & Johnson’s one-dose vaccine], you get a booster after 2 months. If you got Moderna, you can get a booster at 6 months or beyond,” she said during a media briefing.

What is new, she said, is “if you got Pfizer as your primary series, you can get a booster at 5 months or beyond.”
 

A lower risk of myocarditis?

Asked about concerns about the risk of myocarditis with vaccination in the 12- to 15-year age group, Dr. Woodcock said they expect it would be “extremely rare with the third dose.”

“We have the real-world evidence from the Israeli experience to help us with that analysis,” she said.

The data so far consistently points to a higher risk of myocarditis after a second mRNA vaccine dose among males, from teenagers to 30-year-olds, with a peak at about 16 to 17 years of age, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said during the media call.

The risk of myocarditis is about 2 to 3 times higher after a second vaccine dose, compared to a booster shot, Dr. Marks said, based on available data. It may be related to the closer dose timing of the second dose versus a third, he added.

“The inference here is that on the risk of myocarditis with third doses in the 12- to 15-year age range is likely to be quite acceptable,” he said.

Dr. Marks also pointed out that most cases of myocarditis clear up quickly.

“We’re not seeing long-lasting effects. That’s not to say that we don’t care about this and that it’s not important,” he said.

“But what it is saying is that in the setting of a tremendous number of Omicron and Delta cases in this country, the potential benefits of getting vaccinated in this age group outweigh that risk,” Dr. Marks said. “We can look at that risk-benefit and still feel comfortable.”

He said that “the really overwhelming majority of these cases, 98%, have been mild” -- shown by a 1-day median hospital stay.

Even so, the FDA plans to continue monitoring for the risk of myocarditis “very closely,” he said.

Interestingly, swollen underarm lymph nodes were seen more frequently after the booster dose than after the second dose of a two-dose primary series, the FDA said.

Reducing the time between primary vaccination with the Pfizer vaccine -- two initial doses -- and the booster shot from 6 months to 5 months is based on decreasing efficacy data that the drugmaker submitted to the FDA.

The 5-month interval was evaluated in a study from Israel published Dec. 21 in the New England Journal of Medicine .
 

Mixing and matching vaccines

Less clear at the moment is guidance about boosters for people who opted to mix and match their primary vaccine series.

“There was a mix-and-match study that was done which showed that in some cases, the mixing and matching … of an adenoviral record vaccine and an mRNA vaccine seem to give a very good immune response,” Dr. Marks said.

Once more data comes in on mixing and matching, “we’ll analyze them and then potentially make recommendations,” he said.
 

‘It’s not too late’

No federal government media briefing on COVID-19 would be complete without a plea for the unvaccinated to get immunized.

“We’re talking a lot about boosters right now, but it’s not too late for those who have not gotten a vaccine to get a vaccine,” Dr. Marks said, referring to the tens of millions of Americans who remain unvaccinated at the beginning of 2022.

“We know from our previous studies that even a single dose of the vaccine -- and probably two doses -- can help prevent the worst outcomes from COVID-19, including hospitalization and death.”

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

Robert M. Califf, MD, plans to take a close look at federal policies on opioid prescriptions in his expected second turn as the top U.S. regulator of medical products, as well as keep closer tabs on the performance of drugs cleared with accelerated approvals.

Catherine Hackett/Frontline Medical News

Dr. Califf on Tuesday fielded questions at a Senate hearing about his nomination by President Joe Biden to serve as administrator of the U.S. Food and Drug Administration, a role in which he served in the Obama administration. He also spoke about the need to bolster the nation’s ability to maintain an adequate supply of key medical products, including drugs.

Members of the Senate Health, Education, Labor and Pensions Committee, which is handling Dr. Califf’s nomination, were largely cordial and supportive during the hearing. Sen. Patty Murray (D-Wash.), the committee chair, and the panel’s top Republican, Sen. Richard Burr of North Carolina, addressed Dr. Califf during the hearing as if he would soon serve again as the FDA’s leader. Both were among the senators who voted 89-4 to confirm Dr. Califf in a February 2016 vote.

Dr. Califf “was previously confirmed to lead FDA in an overwhelming bipartisan vote, and I look forward to working with him again to ensure FDA continues to protect families across the country, uphold the gold standard of safety and effectiveness, and put science and data first,” Sen. Murray said.

Less enthusiastic about Dr. Califf was Sen. Bernie Sanders (I-VT), who was among the seven senators who did not vote on Dr. Califf’s nomination in 2016.

Sen. Sanders objected in 2016 to Dr. Califf’s ties to the pharmaceutical industry, and he did so again Tuesday. A noted leader in conducting clinical trials, Dr. Califf has worked with many drugmakers. But at the hearing, Dr. Califf said he concurs with Sen. Sanders on an idea strongly opposed by the pharmaceutical industry.

In response to Sen. Sanders’ question, Dr. Califf said he already is “on record as being in favor of Medicare negotiating with the industry on prices.”

The FDA would not take direct part in negotiations, as this work would be handled by the Centers for Medicare & Medicaid Services. Democrats want to give Medicare some negotiating authority through their sweeping Build Back Better Act.

People in the United States are dismayed over both the cost of prescription drugs and the widespread distribution of prescription painkillers that helped fuel the current opioid epidemic, Sen. Sanders told Dr. Califf. Many people will be concerned about an FDA commissioner who has benefited from close ties to the industry, Sen. Sanders said.

“How are they going to believe that you’re going to be an independent and strong voice against this enormously powerful, special interest?” Sen. Sanders asked.

“I’m totally with you on the concept that the price of pharmaceuticals is way too high in this country,” Dr. Califf said in reply.

Dr. Califf was paid $2.7 million in salary and bonus by Verily Life Sciences, the biomedical research organization operated by Alphabet, parent company of Google, according to his federal financial disclosure. He also reported holding board positions with pharmaceutical companies AmyriAD and Centessa Pharmaceuticals.

Bloomberg Government reported that Dr. Califf has ties to about 16 other research organizations and biotech companies. Bloomberg Government also said that, in his earlier FDA service, Dr. Califf kept a whiteboard in his office that listed all the activities and projects that required his recusal, citing as a source Howard Sklamberg, who was a deputy commissioner under Dr. Califf.

“He was very, very, very careful,” Mr. Sklamberg, who’s now an attorney at Arnold & Porter LLP, told Bloomberg Government.
 

‘Work to do’ on opioids

Senators looped back repeatedly to the topic of opioids during Dr. Califf’s hearing, reflecting deep concerns about the FDA’s efforts to warn of the risks of prescription painkillers.

There were an estimated 100,306 drug overdose deaths in the United States in the 12 months ending in April, an increase of 28.5% from the 78,056 deaths during the same period the year before, according to the Centers for Disease Control and Prevention.

Dr. Califf said he plans to focus on what information the FDA conveys to the public about the risks of prescription painkillers, including a look at what the labels for these products say.

“I am committed to do a comprehensive review of the status of opioids, early in my tenure,” Dr. Califf said.

Dr. Califf indicated that physicians are still too quick to provide excess doses of these medicines, despite years of efforts to restrain their use. He said he knows relatives who were given 30-day prescriptions for opioids after minor surgery.

“So I know we have work to do,” Dr. Califf said.

Concerns about the FDA’s previous work in managing opioids has led to protests from a few Democratic senators about the prospect of President Biden nominating the acting FDA commissioner, Janet Woodcock, MD, for the permanent post.

At the hearing, Sen. Ben Ray Luján (D-NM) raised the case of the FDA’s approval of the powerful Zohydro painkiller. The agency approved that drug despite an 11-2 vote against it by the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee.

Sen. Luján asked Dr. Califf what he would do if an FDA advisory committee voted “overwhelmingly” against recommending approval of a medicine, as happened in the Zohydro case.

While not mentioned by Sen. Luján in this exchange during the hearing with Dr. Califf, the FDA staff’s rejection of recommendations of advisory committees has been a growing concern among researchers.

The agency last year approved aducanumab (Aduhelm, Biogen), a drug for Alzheimer’s disease, dismissing the advice of its Peripheral and Central Nervous System Drugs Advisory Committee. That decision triggered the resignation of several members of the panel. The FDA staff also earlier rejected the conclusion the majority of members of the same advisory committee offered in 2016 on eteplirsen (Exondys 51, Sarepta), a drug for Duchenne muscular dystrophy.

Dr. Califf told Sen. Luján he had done recent research into how often the FDA staff does not concur with the recommendations of an advisory committee. He said the FDA takes a different course of action in about 25% of cases. In about three-quarters of those cases, the FDA staff opts for a “more stringent” approach regarding allowing the public access to the drug, as opposed to a more generous one as seen in the Zohydro, Aduhelm, and Exondys 51 cases.

Still, Dr. Califf said that when there’s an 11-2 advisory committee vote against recommendation of a product, “the leaders at FDA really need to take a close look” at what’s happening.

Question on accelerated approvals

The FDA’s approval of aducanumab drew attention to a debate already underway about conditional clearances known as accelerated approvals.

The FDA has used this path since the 1990s to speed access to drugs for serious conditions. The trade-off for early access is that the agency sometimes makes the wrong call based on initial findings, and clears a medicine later found not to benefit patients as expected.

The FDA’s cancer division is in the midst of public efforts to address cases where drugmakers have not been able to deliver studies that support accelerated approvals of their oncology drugs. In addition, the Office of Inspector General of the U.S. Department of Health & Human Services announced in August that it is reviewing the FDA’s handling of the accelerated approval process.

At Tuesday’s hearing, Sen. Burr grilled Dr. Califf about how he would respond to calls to change how the FDA handles the accelerated-approval process.

“Can you commit to me and to patients who may rely on cutting-edge treatments that you will not support efforts to narrow this pathway or raise the bar for drugs to be approved under those pathways?” Burr asked Califf.

Dr. Califf responded by saying he was “a fan of accelerated approval – for the right conditions.”

Earlier, in his opening statement, Dr. Califf had said his mother benefited directly from the accelerated approval of new drugs for multiple myeloma. Dr. Califf told Sen. Burr that he had spent “countless hours with patient groups” and understands the need to speed the approval of medicines for serious diseases.

But the FDA also has to make sure it holds up its end of the bargain struck with accelerated approvals. This involves checking on how these medicines work once they are marketed.

“We’re accepting that there’s more uncertainty,” Dr. Califf said. “That means we’ve got to have a better system to evaluate these products as they’re used on the market. And I think there are ways that we can do that now. Technology is making this possible in ways that it just was not possible before.”
 

Worries about the medical supply chain

Sen. Susan Collins (R-Maine) asked Dr. Califf about the vulnerability of the U.S. medical system to disruptions of the supply chain. She raised concerns about China’s dominance in antibiotic manufacturing as an example. She asked if Congress could do more to encourage domestic manufacturing of medical supplies, such as by offering tax incentives.

Dr. Califf told Sen. Collins he shared her concern about the U.S. manufacturing of ingredients used in both branded and generic drugs. He said he recently has served on a committee of the National Academy of Medicine that is examining supply chain issues.

This committee will soon release a report with specific recommendations, Dr. Califf said.

“We don’t have enough competitive entities in what’s become sort of a commodity business” of drug manufacturing, Dr. Califf said. “So we need a number of steps to make the system more resilient.”

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

Robert M. Califf, MD, plans to take a close look at federal policies on opioid prescriptions in his expected second turn as the top U.S. regulator of medical products, as well as keep closer tabs on the performance of drugs cleared with accelerated approvals.

Catherine Hackett/Frontline Medical News

Dr. Califf on Tuesday fielded questions at a Senate hearing about his nomination by President Joe Biden to serve as administrator of the U.S. Food and Drug Administration, a role in which he served in the Obama administration. He also spoke about the need to bolster the nation’s ability to maintain an adequate supply of key medical products, including drugs.

Members of the Senate Health, Education, Labor and Pensions Committee, which is handling Dr. Califf’s nomination, were largely cordial and supportive during the hearing. Sen. Patty Murray (D-Wash.), the committee chair, and the panel’s top Republican, Sen. Richard Burr of North Carolina, addressed Dr. Califf during the hearing as if he would soon serve again as the FDA’s leader. Both were among the senators who voted 89-4 to confirm Dr. Califf in a February 2016 vote.

Dr. Califf “was previously confirmed to lead FDA in an overwhelming bipartisan vote, and I look forward to working with him again to ensure FDA continues to protect families across the country, uphold the gold standard of safety and effectiveness, and put science and data first,” Sen. Murray said.

Less enthusiastic about Dr. Califf was Sen. Bernie Sanders (I-VT), who was among the seven senators who did not vote on Dr. Califf’s nomination in 2016.

Sen. Sanders objected in 2016 to Dr. Califf’s ties to the pharmaceutical industry, and he did so again Tuesday. A noted leader in conducting clinical trials, Dr. Califf has worked with many drugmakers. But at the hearing, Dr. Califf said he concurs with Sen. Sanders on an idea strongly opposed by the pharmaceutical industry.

In response to Sen. Sanders’ question, Dr. Califf said he already is “on record as being in favor of Medicare negotiating with the industry on prices.”

The FDA would not take direct part in negotiations, as this work would be handled by the Centers for Medicare & Medicaid Services. Democrats want to give Medicare some negotiating authority through their sweeping Build Back Better Act.

People in the United States are dismayed over both the cost of prescription drugs and the widespread distribution of prescription painkillers that helped fuel the current opioid epidemic, Sen. Sanders told Dr. Califf. Many people will be concerned about an FDA commissioner who has benefited from close ties to the industry, Sen. Sanders said.

“How are they going to believe that you’re going to be an independent and strong voice against this enormously powerful, special interest?” Sen. Sanders asked.

“I’m totally with you on the concept that the price of pharmaceuticals is way too high in this country,” Dr. Califf said in reply.

Dr. Califf was paid $2.7 million in salary and bonus by Verily Life Sciences, the biomedical research organization operated by Alphabet, parent company of Google, according to his federal financial disclosure. He also reported holding board positions with pharmaceutical companies AmyriAD and Centessa Pharmaceuticals.

Bloomberg Government reported that Dr. Califf has ties to about 16 other research organizations and biotech companies. Bloomberg Government also said that, in his earlier FDA service, Dr. Califf kept a whiteboard in his office that listed all the activities and projects that required his recusal, citing as a source Howard Sklamberg, who was a deputy commissioner under Dr. Califf.

“He was very, very, very careful,” Mr. Sklamberg, who’s now an attorney at Arnold & Porter LLP, told Bloomberg Government.
 

‘Work to do’ on opioids

Senators looped back repeatedly to the topic of opioids during Dr. Califf’s hearing, reflecting deep concerns about the FDA’s efforts to warn of the risks of prescription painkillers.

There were an estimated 100,306 drug overdose deaths in the United States in the 12 months ending in April, an increase of 28.5% from the 78,056 deaths during the same period the year before, according to the Centers for Disease Control and Prevention.

Dr. Califf said he plans to focus on what information the FDA conveys to the public about the risks of prescription painkillers, including a look at what the labels for these products say.

“I am committed to do a comprehensive review of the status of opioids, early in my tenure,” Dr. Califf said.

Dr. Califf indicated that physicians are still too quick to provide excess doses of these medicines, despite years of efforts to restrain their use. He said he knows relatives who were given 30-day prescriptions for opioids after minor surgery.

“So I know we have work to do,” Dr. Califf said.

Concerns about the FDA’s previous work in managing opioids has led to protests from a few Democratic senators about the prospect of President Biden nominating the acting FDA commissioner, Janet Woodcock, MD, for the permanent post.

At the hearing, Sen. Ben Ray Luján (D-NM) raised the case of the FDA’s approval of the powerful Zohydro painkiller. The agency approved that drug despite an 11-2 vote against it by the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee.

Sen. Luján asked Dr. Califf what he would do if an FDA advisory committee voted “overwhelmingly” against recommending approval of a medicine, as happened in the Zohydro case.

While not mentioned by Sen. Luján in this exchange during the hearing with Dr. Califf, the FDA staff’s rejection of recommendations of advisory committees has been a growing concern among researchers.

The agency last year approved aducanumab (Aduhelm, Biogen), a drug for Alzheimer’s disease, dismissing the advice of its Peripheral and Central Nervous System Drugs Advisory Committee. That decision triggered the resignation of several members of the panel. The FDA staff also earlier rejected the conclusion the majority of members of the same advisory committee offered in 2016 on eteplirsen (Exondys 51, Sarepta), a drug for Duchenne muscular dystrophy.

Dr. Califf told Sen. Luján he had done recent research into how often the FDA staff does not concur with the recommendations of an advisory committee. He said the FDA takes a different course of action in about 25% of cases. In about three-quarters of those cases, the FDA staff opts for a “more stringent” approach regarding allowing the public access to the drug, as opposed to a more generous one as seen in the Zohydro, Aduhelm, and Exondys 51 cases.

Still, Dr. Califf said that when there’s an 11-2 advisory committee vote against recommendation of a product, “the leaders at FDA really need to take a close look” at what’s happening.

Question on accelerated approvals

The FDA’s approval of aducanumab drew attention to a debate already underway about conditional clearances known as accelerated approvals.

The FDA has used this path since the 1990s to speed access to drugs for serious conditions. The trade-off for early access is that the agency sometimes makes the wrong call based on initial findings, and clears a medicine later found not to benefit patients as expected.

The FDA’s cancer division is in the midst of public efforts to address cases where drugmakers have not been able to deliver studies that support accelerated approvals of their oncology drugs. In addition, the Office of Inspector General of the U.S. Department of Health & Human Services announced in August that it is reviewing the FDA’s handling of the accelerated approval process.

At Tuesday’s hearing, Sen. Burr grilled Dr. Califf about how he would respond to calls to change how the FDA handles the accelerated-approval process.

“Can you commit to me and to patients who may rely on cutting-edge treatments that you will not support efforts to narrow this pathway or raise the bar for drugs to be approved under those pathways?” Burr asked Califf.

Dr. Califf responded by saying he was “a fan of accelerated approval – for the right conditions.”

Earlier, in his opening statement, Dr. Califf had said his mother benefited directly from the accelerated approval of new drugs for multiple myeloma. Dr. Califf told Sen. Burr that he had spent “countless hours with patient groups” and understands the need to speed the approval of medicines for serious diseases.

But the FDA also has to make sure it holds up its end of the bargain struck with accelerated approvals. This involves checking on how these medicines work once they are marketed.

“We’re accepting that there’s more uncertainty,” Dr. Califf said. “That means we’ve got to have a better system to evaluate these products as they’re used on the market. And I think there are ways that we can do that now. Technology is making this possible in ways that it just was not possible before.”
 

Worries about the medical supply chain

Sen. Susan Collins (R-Maine) asked Dr. Califf about the vulnerability of the U.S. medical system to disruptions of the supply chain. She raised concerns about China’s dominance in antibiotic manufacturing as an example. She asked if Congress could do more to encourage domestic manufacturing of medical supplies, such as by offering tax incentives.

Dr. Califf told Sen. Collins he shared her concern about the U.S. manufacturing of ingredients used in both branded and generic drugs. He said he recently has served on a committee of the National Academy of Medicine that is examining supply chain issues.

This committee will soon release a report with specific recommendations, Dr. Califf said.

“We don’t have enough competitive entities in what’s become sort of a commodity business” of drug manufacturing, Dr. Califf said. “So we need a number of steps to make the system more resilient.”

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

Robert M. Califf, MD, plans to take a close look at federal policies on opioid prescriptions in his expected second turn as the top U.S. regulator of medical products, as well as keep closer tabs on the performance of drugs cleared with accelerated approvals.

Catherine Hackett/Frontline Medical News

Dr. Califf on Tuesday fielded questions at a Senate hearing about his nomination by President Joe Biden to serve as administrator of the U.S. Food and Drug Administration, a role in which he served in the Obama administration. He also spoke about the need to bolster the nation’s ability to maintain an adequate supply of key medical products, including drugs.

Members of the Senate Health, Education, Labor and Pensions Committee, which is handling Dr. Califf’s nomination, were largely cordial and supportive during the hearing. Sen. Patty Murray (D-Wash.), the committee chair, and the panel’s top Republican, Sen. Richard Burr of North Carolina, addressed Dr. Califf during the hearing as if he would soon serve again as the FDA’s leader. Both were among the senators who voted 89-4 to confirm Dr. Califf in a February 2016 vote.

Dr. Califf “was previously confirmed to lead FDA in an overwhelming bipartisan vote, and I look forward to working with him again to ensure FDA continues to protect families across the country, uphold the gold standard of safety and effectiveness, and put science and data first,” Sen. Murray said.

Less enthusiastic about Dr. Califf was Sen. Bernie Sanders (I-VT), who was among the seven senators who did not vote on Dr. Califf’s nomination in 2016.

Sen. Sanders objected in 2016 to Dr. Califf’s ties to the pharmaceutical industry, and he did so again Tuesday. A noted leader in conducting clinical trials, Dr. Califf has worked with many drugmakers. But at the hearing, Dr. Califf said he concurs with Sen. Sanders on an idea strongly opposed by the pharmaceutical industry.

In response to Sen. Sanders’ question, Dr. Califf said he already is “on record as being in favor of Medicare negotiating with the industry on prices.”

The FDA would not take direct part in negotiations, as this work would be handled by the Centers for Medicare & Medicaid Services. Democrats want to give Medicare some negotiating authority through their sweeping Build Back Better Act.

People in the United States are dismayed over both the cost of prescription drugs and the widespread distribution of prescription painkillers that helped fuel the current opioid epidemic, Sen. Sanders told Dr. Califf. Many people will be concerned about an FDA commissioner who has benefited from close ties to the industry, Sen. Sanders said.

“How are they going to believe that you’re going to be an independent and strong voice against this enormously powerful, special interest?” Sen. Sanders asked.

“I’m totally with you on the concept that the price of pharmaceuticals is way too high in this country,” Dr. Califf said in reply.

Dr. Califf was paid $2.7 million in salary and bonus by Verily Life Sciences, the biomedical research organization operated by Alphabet, parent company of Google, according to his federal financial disclosure. He also reported holding board positions with pharmaceutical companies AmyriAD and Centessa Pharmaceuticals.

Bloomberg Government reported that Dr. Califf has ties to about 16 other research organizations and biotech companies. Bloomberg Government also said that, in his earlier FDA service, Dr. Califf kept a whiteboard in his office that listed all the activities and projects that required his recusal, citing as a source Howard Sklamberg, who was a deputy commissioner under Dr. Califf.

“He was very, very, very careful,” Mr. Sklamberg, who’s now an attorney at Arnold & Porter LLP, told Bloomberg Government.
 

‘Work to do’ on opioids

Senators looped back repeatedly to the topic of opioids during Dr. Califf’s hearing, reflecting deep concerns about the FDA’s efforts to warn of the risks of prescription painkillers.

There were an estimated 100,306 drug overdose deaths in the United States in the 12 months ending in April, an increase of 28.5% from the 78,056 deaths during the same period the year before, according to the Centers for Disease Control and Prevention.

Dr. Califf said he plans to focus on what information the FDA conveys to the public about the risks of prescription painkillers, including a look at what the labels for these products say.

“I am committed to do a comprehensive review of the status of opioids, early in my tenure,” Dr. Califf said.

Dr. Califf indicated that physicians are still too quick to provide excess doses of these medicines, despite years of efforts to restrain their use. He said he knows relatives who were given 30-day prescriptions for opioids after minor surgery.

“So I know we have work to do,” Dr. Califf said.

Concerns about the FDA’s previous work in managing opioids has led to protests from a few Democratic senators about the prospect of President Biden nominating the acting FDA commissioner, Janet Woodcock, MD, for the permanent post.

At the hearing, Sen. Ben Ray Luján (D-NM) raised the case of the FDA’s approval of the powerful Zohydro painkiller. The agency approved that drug despite an 11-2 vote against it by the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee.

Sen. Luján asked Dr. Califf what he would do if an FDA advisory committee voted “overwhelmingly” against recommending approval of a medicine, as happened in the Zohydro case.

While not mentioned by Sen. Luján in this exchange during the hearing with Dr. Califf, the FDA staff’s rejection of recommendations of advisory committees has been a growing concern among researchers.

The agency last year approved aducanumab (Aduhelm, Biogen), a drug for Alzheimer’s disease, dismissing the advice of its Peripheral and Central Nervous System Drugs Advisory Committee. That decision triggered the resignation of several members of the panel. The FDA staff also earlier rejected the conclusion the majority of members of the same advisory committee offered in 2016 on eteplirsen (Exondys 51, Sarepta), a drug for Duchenne muscular dystrophy.

Dr. Califf told Sen. Luján he had done recent research into how often the FDA staff does not concur with the recommendations of an advisory committee. He said the FDA takes a different course of action in about 25% of cases. In about three-quarters of those cases, the FDA staff opts for a “more stringent” approach regarding allowing the public access to the drug, as opposed to a more generous one as seen in the Zohydro, Aduhelm, and Exondys 51 cases.

Still, Dr. Califf said that when there’s an 11-2 advisory committee vote against recommendation of a product, “the leaders at FDA really need to take a close look” at what’s happening.

Question on accelerated approvals

The FDA’s approval of aducanumab drew attention to a debate already underway about conditional clearances known as accelerated approvals.

The FDA has used this path since the 1990s to speed access to drugs for serious conditions. The trade-off for early access is that the agency sometimes makes the wrong call based on initial findings, and clears a medicine later found not to benefit patients as expected.

The FDA’s cancer division is in the midst of public efforts to address cases where drugmakers have not been able to deliver studies that support accelerated approvals of their oncology drugs. In addition, the Office of Inspector General of the U.S. Department of Health & Human Services announced in August that it is reviewing the FDA’s handling of the accelerated approval process.

At Tuesday’s hearing, Sen. Burr grilled Dr. Califf about how he would respond to calls to change how the FDA handles the accelerated-approval process.

“Can you commit to me and to patients who may rely on cutting-edge treatments that you will not support efforts to narrow this pathway or raise the bar for drugs to be approved under those pathways?” Burr asked Califf.

Dr. Califf responded by saying he was “a fan of accelerated approval – for the right conditions.”

Earlier, in his opening statement, Dr. Califf had said his mother benefited directly from the accelerated approval of new drugs for multiple myeloma. Dr. Califf told Sen. Burr that he had spent “countless hours with patient groups” and understands the need to speed the approval of medicines for serious diseases.

But the FDA also has to make sure it holds up its end of the bargain struck with accelerated approvals. This involves checking on how these medicines work once they are marketed.

“We’re accepting that there’s more uncertainty,” Dr. Califf said. “That means we’ve got to have a better system to evaluate these products as they’re used on the market. And I think there are ways that we can do that now. Technology is making this possible in ways that it just was not possible before.”
 

Worries about the medical supply chain

Sen. Susan Collins (R-Maine) asked Dr. Califf about the vulnerability of the U.S. medical system to disruptions of the supply chain. She raised concerns about China’s dominance in antibiotic manufacturing as an example. She asked if Congress could do more to encourage domestic manufacturing of medical supplies, such as by offering tax incentives.

Dr. Califf told Sen. Collins he shared her concern about the U.S. manufacturing of ingredients used in both branded and generic drugs. He said he recently has served on a committee of the National Academy of Medicine that is examining supply chain issues.

This committee will soon release a report with specific recommendations, Dr. Califf said.

“We don’t have enough competitive entities in what’s become sort of a commodity business” of drug manufacturing, Dr. Califf said. “So we need a number of steps to make the system more resilient.”

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

A recent study examined projected career earnings between the genders in a largely community-based physician population, finding a difference of about $2 million in career earnings. That a gender pay gap exists in medicine is not news – but the manner in which this study was done, the investigators’ ability to control for a number of confounding variables, and the size of the study group (over 80,000) are newsworthy.

Some of the key findings include that gender pay gaps start with your first job, and you never close the gap, even as you gain experience and efficiency. Also, the more highly remunerated your specialty, the larger the gap. The gender pay gap joins a growing list of inequities within health care. Although physician compensation is not the most important, given that nearly all physicians are well-paid, and we have much more significant inequities that lead to direct patient harm, the reasons for this discrepancy warrant further consideration.

When I was first being educated about social inequity as part of work in social determinants of health, I made the error of using “inequality” and “inequity” interchangeably. The subtle yet important difference between the two terms was quickly described to me. Inequality is a gastroenterologist getting paid more money to do a colonoscopy than a family physician. Inequity is a female gastroenterologist getting paid less than a male gastroenterologist. Global Health Europe boldly identifies that “inequity is the result of failure.” In looking at the inequity inherent in the gender pay gap, I consider what failed and why.

I’m currently making a major career change, leaving an executive leadership position to return to full-time clinical practice. There is a significant pay decrease that will accompany this change because I am in a primary care specialty. Beyond that, I am considering two employment contracts from different systems to do a similar clinical role.

One of the questions my husband asked was which will pay more over the long run. This is difficult to discern because the compensation formula each health system uses is different, even though they are based on standard national benchmarking data. It is possible that women, in general, are like I am and look for factors other than compensation to make a job decision – assuming, like I do, that it will be close enough to not matter or is generally fair. In fact, while compensation is most certainly a consideration for me, once I determined that it was likely to be in the same ballpark, I stopped comparing. Even as the sole breadwinner in our family, I take this (probably faulty) approach.
 

It’s time to reconsider how we pay physicians

Women may be more likely to gloss over compensation details that men evaluate and negotiate carefully. To change this, women must first take responsibility for being an active, informed, and engaged part of compensation negotiations. In addition, employers who value gender pay equity must negotiate in good faith, keeping in mind the well-described vulnerabilities in discussions about pay. Finally, male and female mentors and leaders should actively coach female physicians on how to approach these conversations with confidence and skill.

In primary care, female physicians spend, on average, about 15% more time with their patients during a visit. Despite spending as much time in clinic seeing patients per week, they see fewer patients, thereby generating less revenue. For compensation plans that are based on productivity, the extra time spent costs money. In this case, it costs the female physicians lost compensation.

The way in which women are more likely to practice medicine, which includes the amount of time they spend with patients, may affect clinical outcomes without directly increasing productivity. A 2017 study demonstrated that elderly patients had lower rates of mortality and readmission when cared for by a female rather than a male physician. These findings require health systems to critically evaluate what compensation plans value and to promote an appropriate balance between quality of care, quantity of care, and style of care.

Although I’ve seen gender pay inequity as blatant as two different salaries for physicians doing the same work – one male and one female – I think this is uncommon. Like many forms of inequity, the outputs are often related to a failed system rather than solely a series of individual failures. Making compensation formulas gender-blind is an important step – but it is only the first step, not the last. Recognizing that the structure of a compensation formula may be biased toward a style of medical practice more likely to be espoused by one gender is necessary as well.

The data, including the findings of this recent study, clearly identify the gender pay gap that exists in medicine, as it does in many other fields, and that it is not explainable solely by differences in specialties, work hours, family status, or title.

To address the inequity, it is imperative that women engage with employers and leaders to both understand and develop skills around effective and appropriate compensation negotiation. Recognizing that compensation plans, especially those built on productivity models, may fail to place adequate value on gender-specific practice styles.

Jennifer Frank is a family physician, physician leader, wife, and mother in Northeast Wisconsin.

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

A recent study examined projected career earnings between the genders in a largely community-based physician population, finding a difference of about $2 million in career earnings. That a gender pay gap exists in medicine is not news – but the manner in which this study was done, the investigators’ ability to control for a number of confounding variables, and the size of the study group (over 80,000) are newsworthy.

Some of the key findings include that gender pay gaps start with your first job, and you never close the gap, even as you gain experience and efficiency. Also, the more highly remunerated your specialty, the larger the gap. The gender pay gap joins a growing list of inequities within health care. Although physician compensation is not the most important, given that nearly all physicians are well-paid, and we have much more significant inequities that lead to direct patient harm, the reasons for this discrepancy warrant further consideration.

When I was first being educated about social inequity as part of work in social determinants of health, I made the error of using “inequality” and “inequity” interchangeably. The subtle yet important difference between the two terms was quickly described to me. Inequality is a gastroenterologist getting paid more money to do a colonoscopy than a family physician. Inequity is a female gastroenterologist getting paid less than a male gastroenterologist. Global Health Europe boldly identifies that “inequity is the result of failure.” In looking at the inequity inherent in the gender pay gap, I consider what failed and why.

I’m currently making a major career change, leaving an executive leadership position to return to full-time clinical practice. There is a significant pay decrease that will accompany this change because I am in a primary care specialty. Beyond that, I am considering two employment contracts from different systems to do a similar clinical role.

One of the questions my husband asked was which will pay more over the long run. This is difficult to discern because the compensation formula each health system uses is different, even though they are based on standard national benchmarking data. It is possible that women, in general, are like I am and look for factors other than compensation to make a job decision – assuming, like I do, that it will be close enough to not matter or is generally fair. In fact, while compensation is most certainly a consideration for me, once I determined that it was likely to be in the same ballpark, I stopped comparing. Even as the sole breadwinner in our family, I take this (probably faulty) approach.
 

It’s time to reconsider how we pay physicians

Women may be more likely to gloss over compensation details that men evaluate and negotiate carefully. To change this, women must first take responsibility for being an active, informed, and engaged part of compensation negotiations. In addition, employers who value gender pay equity must negotiate in good faith, keeping in mind the well-described vulnerabilities in discussions about pay. Finally, male and female mentors and leaders should actively coach female physicians on how to approach these conversations with confidence and skill.

In primary care, female physicians spend, on average, about 15% more time with their patients during a visit. Despite spending as much time in clinic seeing patients per week, they see fewer patients, thereby generating less revenue. For compensation plans that are based on productivity, the extra time spent costs money. In this case, it costs the female physicians lost compensation.

The way in which women are more likely to practice medicine, which includes the amount of time they spend with patients, may affect clinical outcomes without directly increasing productivity. A 2017 study demonstrated that elderly patients had lower rates of mortality and readmission when cared for by a female rather than a male physician. These findings require health systems to critically evaluate what compensation plans value and to promote an appropriate balance between quality of care, quantity of care, and style of care.

Although I’ve seen gender pay inequity as blatant as two different salaries for physicians doing the same work – one male and one female – I think this is uncommon. Like many forms of inequity, the outputs are often related to a failed system rather than solely a series of individual failures. Making compensation formulas gender-blind is an important step – but it is only the first step, not the last. Recognizing that the structure of a compensation formula may be biased toward a style of medical practice more likely to be espoused by one gender is necessary as well.

The data, including the findings of this recent study, clearly identify the gender pay gap that exists in medicine, as it does in many other fields, and that it is not explainable solely by differences in specialties, work hours, family status, or title.

To address the inequity, it is imperative that women engage with employers and leaders to both understand and develop skills around effective and appropriate compensation negotiation. Recognizing that compensation plans, especially those built on productivity models, may fail to place adequate value on gender-specific practice styles.

Jennifer Frank is a family physician, physician leader, wife, and mother in Northeast Wisconsin.

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

A recent study examined projected career earnings between the genders in a largely community-based physician population, finding a difference of about $2 million in career earnings. That a gender pay gap exists in medicine is not news – but the manner in which this study was done, the investigators’ ability to control for a number of confounding variables, and the size of the study group (over 80,000) are newsworthy.

Some of the key findings include that gender pay gaps start with your first job, and you never close the gap, even as you gain experience and efficiency. Also, the more highly remunerated your specialty, the larger the gap. The gender pay gap joins a growing list of inequities within health care. Although physician compensation is not the most important, given that nearly all physicians are well-paid, and we have much more significant inequities that lead to direct patient harm, the reasons for this discrepancy warrant further consideration.

When I was first being educated about social inequity as part of work in social determinants of health, I made the error of using “inequality” and “inequity” interchangeably. The subtle yet important difference between the two terms was quickly described to me. Inequality is a gastroenterologist getting paid more money to do a colonoscopy than a family physician. Inequity is a female gastroenterologist getting paid less than a male gastroenterologist. Global Health Europe boldly identifies that “inequity is the result of failure.” In looking at the inequity inherent in the gender pay gap, I consider what failed and why.

I’m currently making a major career change, leaving an executive leadership position to return to full-time clinical practice. There is a significant pay decrease that will accompany this change because I am in a primary care specialty. Beyond that, I am considering two employment contracts from different systems to do a similar clinical role.

One of the questions my husband asked was which will pay more over the long run. This is difficult to discern because the compensation formula each health system uses is different, even though they are based on standard national benchmarking data. It is possible that women, in general, are like I am and look for factors other than compensation to make a job decision – assuming, like I do, that it will be close enough to not matter or is generally fair. In fact, while compensation is most certainly a consideration for me, once I determined that it was likely to be in the same ballpark, I stopped comparing. Even as the sole breadwinner in our family, I take this (probably faulty) approach.
 

It’s time to reconsider how we pay physicians

Women may be more likely to gloss over compensation details that men evaluate and negotiate carefully. To change this, women must first take responsibility for being an active, informed, and engaged part of compensation negotiations. In addition, employers who value gender pay equity must negotiate in good faith, keeping in mind the well-described vulnerabilities in discussions about pay. Finally, male and female mentors and leaders should actively coach female physicians on how to approach these conversations with confidence and skill.

In primary care, female physicians spend, on average, about 15% more time with their patients during a visit. Despite spending as much time in clinic seeing patients per week, they see fewer patients, thereby generating less revenue. For compensation plans that are based on productivity, the extra time spent costs money. In this case, it costs the female physicians lost compensation.

The way in which women are more likely to practice medicine, which includes the amount of time they spend with patients, may affect clinical outcomes without directly increasing productivity. A 2017 study demonstrated that elderly patients had lower rates of mortality and readmission when cared for by a female rather than a male physician. These findings require health systems to critically evaluate what compensation plans value and to promote an appropriate balance between quality of care, quantity of care, and style of care.

Although I’ve seen gender pay inequity as blatant as two different salaries for physicians doing the same work – one male and one female – I think this is uncommon. Like many forms of inequity, the outputs are often related to a failed system rather than solely a series of individual failures. Making compensation formulas gender-blind is an important step – but it is only the first step, not the last. Recognizing that the structure of a compensation formula may be biased toward a style of medical practice more likely to be espoused by one gender is necessary as well.

The data, including the findings of this recent study, clearly identify the gender pay gap that exists in medicine, as it does in many other fields, and that it is not explainable solely by differences in specialties, work hours, family status, or title.

To address the inequity, it is imperative that women engage with employers and leaders to both understand and develop skills around effective and appropriate compensation negotiation. Recognizing that compensation plans, especially those built on productivity models, may fail to place adequate value on gender-specific practice styles.

Jennifer Frank is a family physician, physician leader, wife, and mother in Northeast Wisconsin.

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