Infectious Diseases

When 23 frail elderly patients in Norway died in early 2021 shortly after they had received an mRNA-based vaccine against COVID-19, Norwegian health authorities cautioned physicians to conduct more thorough assessments of patients prior to immunization, and launched an investigation into the safety of the BNT162b2 vaccine (Comirnaty; Pfizer-BioNTech).

Now, the results of that investigation and of a subsequent larger study of nursing home residents in Norway have shown no increased risk for short-term mortality following COVID-19 vaccination in the overall population of elderly patients. The new research also showed clear evidence of a survival benefit compared with the unvaccinated population, Anette Hylen Ranhoff, MD, PhD, said at the annual meeting of the European Geriatric Medicine Society, held in a hybrid format in Athens, Greece, and online.

“We found no evidence of increased short-term mortality among vaccinated older individuals, and particularly not among the nursing home patients,” said Dr. Ranhoff, a senior researcher at the Norwegian Institute of Public Health and professor at University of Bergen, Norway. “But we think that this [lower] mortality risk was most likely a sort of ‘healthy-vaccinee’ effect, which means that people who were a bit more healthy were vaccinated, and not those who were the very, very most frail.”

“We have more or less the same data in France about events, with very high rates of vaccination,” said session moderator Athanase Benetos MD, PhD, professor and chairman of geriatric medicine at the University Hospital of Nancy in France, who was not involved in the study.

“In my department, a month after the end of the vaccination and at the same time while the pandemic in the city was going up, we had a 90% decrease in mortality from COVID in the nursing homes,” he told Dr. Ranhoff.
 

Potential risks

Frail elderly patients were not included in clinical trials of COVID-19 vaccines, and although previous studies have shown a low incidence of local or systemic reactions to vaccination among older people, “we think that quite mild adverse events following vaccination could trigger and destabilize a frail person,” Dr. Ranhoff said.

As reported Jan. 15, 2021, in BMJ, investigation by the Norwegian Medicines Agency (NOMA) into 13 of the 23 reported cases concluded that common adverse reactions associated with mRNA vaccines could have contributed to the deaths of some of the frail elderly patients

Steinar Madsen, MD, NOMA medical director, told BMJ “we are not alarmed or worried about this, because these are very rare occurrences and they occurred in very frail patients with very serious disease.”
 

Health authorities investigate

In response to the report and at the request of the Norwegian Public Health Institute and NOMA, Dr. Ranhoff and colleagues investigated the first 100 deaths among nursing-home residents who received the vaccine. The team consisted of three geriatricians and an infectious disease specialist who sees patients in nursing homes.

They looked at each patient’s clinical course before and after vaccination, their health trajectory and life expectancy at the time of vaccination, new symptoms following vaccination, and the time from vaccination to new symptoms and to death.

In addition, the investigators evaluated Clinical Frailty Scale (CFS) scores for each patient. CFS scores range from 1 (very fit) to 9 (terminally ill, with a life expectancy of less than 6 months who are otherwise evidently frail).

The initial investigation found that among 95 evaluable patients, the association between vaccination and death was “probable” in 10, “possible” in 26, and “unlikely” in 59.

The mean time from vaccination to symptoms was 1.4 days in the probable cases, 2.5 days in the possible cases, and 4.7 days in the unlikely cases.

The mean time from vaccination to death was 3.1, 8.3, and 8.2 days, respectively.

In all three categories, the patients had mean CFS scores ranging from 7.6 to 7.9, putting them in the “severely frail” category, defined as people who are completely dependent for personal care but seem stable and not at high risk for dying.

“We have quite many nursing home residents in Norway, 35,000; more than 80% have dementia, and the mean age is 85 years. We know that approximately 45 people die every day in these nursing homes, and their mean age of death is 87.5 years,” Dr. Ranhoff said.
 

Population-wide study

Dr. Ranhoff and colleagues also looked more broadly into the question of potential vaccine-related mortality in the total population of older people in Norway from the day of vaccination to follow-up at 3 weeks.

They conducted a matched cohort study to investigate the relationship between the mRNA SARS-CoV-2 vaccine and overall death among persons aged 65 and older in the general population, and across four groups: patients receiving home-based care, long-term nursing home patients, short-term nursing home patients, and those not receiving health services.

The researchers identified a total of 967,786 residents of Norway aged 65 and over at the start of the country’s vaccination campaign at the end of December, 2020, and they matched vaccinated individuals with unvaccinated persons based on demographic, geographic, and clinical risk group factors.

Dr. Ranhoff showed Kaplan-Meier survival curves for the total population and for each of the health-service states. In all cases there was a clear survival benefit for vaccinated vs. unvaccinated patients. She did not, however, provide specific numbers or hazard ratios for the differences between vaccinated and unvaccinated individuals in each of the comparisons.

The study was supported by the Norwegian Institute of Public Health. Dr. Ranhoff and Dr. Benetos reported no conflicts of interest.

When 23 frail elderly patients in Norway died in early 2021 shortly after they had received an mRNA-based vaccine against COVID-19, Norwegian health authorities cautioned physicians to conduct more thorough assessments of patients prior to immunization, and launched an investigation into the safety of the BNT162b2 vaccine (Comirnaty; Pfizer-BioNTech).

Now, the results of that investigation and of a subsequent larger study of nursing home residents in Norway have shown no increased risk for short-term mortality following COVID-19 vaccination in the overall population of elderly patients. The new research also showed clear evidence of a survival benefit compared with the unvaccinated population, Anette Hylen Ranhoff, MD, PhD, said at the annual meeting of the European Geriatric Medicine Society, held in a hybrid format in Athens, Greece, and online.

“We found no evidence of increased short-term mortality among vaccinated older individuals, and particularly not among the nursing home patients,” said Dr. Ranhoff, a senior researcher at the Norwegian Institute of Public Health and professor at University of Bergen, Norway. “But we think that this [lower] mortality risk was most likely a sort of ‘healthy-vaccinee’ effect, which means that people who were a bit more healthy were vaccinated, and not those who were the very, very most frail.”

“We have more or less the same data in France about events, with very high rates of vaccination,” said session moderator Athanase Benetos MD, PhD, professor and chairman of geriatric medicine at the University Hospital of Nancy in France, who was not involved in the study.

“In my department, a month after the end of the vaccination and at the same time while the pandemic in the city was going up, we had a 90% decrease in mortality from COVID in the nursing homes,” he told Dr. Ranhoff.
 

Potential risks

Frail elderly patients were not included in clinical trials of COVID-19 vaccines, and although previous studies have shown a low incidence of local or systemic reactions to vaccination among older people, “we think that quite mild adverse events following vaccination could trigger and destabilize a frail person,” Dr. Ranhoff said.

As reported Jan. 15, 2021, in BMJ, investigation by the Norwegian Medicines Agency (NOMA) into 13 of the 23 reported cases concluded that common adverse reactions associated with mRNA vaccines could have contributed to the deaths of some of the frail elderly patients

Steinar Madsen, MD, NOMA medical director, told BMJ “we are not alarmed or worried about this, because these are very rare occurrences and they occurred in very frail patients with very serious disease.”
 

Health authorities investigate

In response to the report and at the request of the Norwegian Public Health Institute and NOMA, Dr. Ranhoff and colleagues investigated the first 100 deaths among nursing-home residents who received the vaccine. The team consisted of three geriatricians and an infectious disease specialist who sees patients in nursing homes.

They looked at each patient’s clinical course before and after vaccination, their health trajectory and life expectancy at the time of vaccination, new symptoms following vaccination, and the time from vaccination to new symptoms and to death.

In addition, the investigators evaluated Clinical Frailty Scale (CFS) scores for each patient. CFS scores range from 1 (very fit) to 9 (terminally ill, with a life expectancy of less than 6 months who are otherwise evidently frail).

The initial investigation found that among 95 evaluable patients, the association between vaccination and death was “probable” in 10, “possible” in 26, and “unlikely” in 59.

The mean time from vaccination to symptoms was 1.4 days in the probable cases, 2.5 days in the possible cases, and 4.7 days in the unlikely cases.

The mean time from vaccination to death was 3.1, 8.3, and 8.2 days, respectively.

In all three categories, the patients had mean CFS scores ranging from 7.6 to 7.9, putting them in the “severely frail” category, defined as people who are completely dependent for personal care but seem stable and not at high risk for dying.

“We have quite many nursing home residents in Norway, 35,000; more than 80% have dementia, and the mean age is 85 years. We know that approximately 45 people die every day in these nursing homes, and their mean age of death is 87.5 years,” Dr. Ranhoff said.
 

Population-wide study

Dr. Ranhoff and colleagues also looked more broadly into the question of potential vaccine-related mortality in the total population of older people in Norway from the day of vaccination to follow-up at 3 weeks.

They conducted a matched cohort study to investigate the relationship between the mRNA SARS-CoV-2 vaccine and overall death among persons aged 65 and older in the general population, and across four groups: patients receiving home-based care, long-term nursing home patients, short-term nursing home patients, and those not receiving health services.

The researchers identified a total of 967,786 residents of Norway aged 65 and over at the start of the country’s vaccination campaign at the end of December, 2020, and they matched vaccinated individuals with unvaccinated persons based on demographic, geographic, and clinical risk group factors.

Dr. Ranhoff showed Kaplan-Meier survival curves for the total population and for each of the health-service states. In all cases there was a clear survival benefit for vaccinated vs. unvaccinated patients. She did not, however, provide specific numbers or hazard ratios for the differences between vaccinated and unvaccinated individuals in each of the comparisons.

The study was supported by the Norwegian Institute of Public Health. Dr. Ranhoff and Dr. Benetos reported no conflicts of interest.

When 23 frail elderly patients in Norway died in early 2021 shortly after they had received an mRNA-based vaccine against COVID-19, Norwegian health authorities cautioned physicians to conduct more thorough assessments of patients prior to immunization, and launched an investigation into the safety of the BNT162b2 vaccine (Comirnaty; Pfizer-BioNTech).

Now, the results of that investigation and of a subsequent larger study of nursing home residents in Norway have shown no increased risk for short-term mortality following COVID-19 vaccination in the overall population of elderly patients. The new research also showed clear evidence of a survival benefit compared with the unvaccinated population, Anette Hylen Ranhoff, MD, PhD, said at the annual meeting of the European Geriatric Medicine Society, held in a hybrid format in Athens, Greece, and online.

“We found no evidence of increased short-term mortality among vaccinated older individuals, and particularly not among the nursing home patients,” said Dr. Ranhoff, a senior researcher at the Norwegian Institute of Public Health and professor at University of Bergen, Norway. “But we think that this [lower] mortality risk was most likely a sort of ‘healthy-vaccinee’ effect, which means that people who were a bit more healthy were vaccinated, and not those who were the very, very most frail.”

“We have more or less the same data in France about events, with very high rates of vaccination,” said session moderator Athanase Benetos MD, PhD, professor and chairman of geriatric medicine at the University Hospital of Nancy in France, who was not involved in the study.

“In my department, a month after the end of the vaccination and at the same time while the pandemic in the city was going up, we had a 90% decrease in mortality from COVID in the nursing homes,” he told Dr. Ranhoff.
 

Potential risks

Frail elderly patients were not included in clinical trials of COVID-19 vaccines, and although previous studies have shown a low incidence of local or systemic reactions to vaccination among older people, “we think that quite mild adverse events following vaccination could trigger and destabilize a frail person,” Dr. Ranhoff said.

As reported Jan. 15, 2021, in BMJ, investigation by the Norwegian Medicines Agency (NOMA) into 13 of the 23 reported cases concluded that common adverse reactions associated with mRNA vaccines could have contributed to the deaths of some of the frail elderly patients

Steinar Madsen, MD, NOMA medical director, told BMJ “we are not alarmed or worried about this, because these are very rare occurrences and they occurred in very frail patients with very serious disease.”
 

Health authorities investigate

In response to the report and at the request of the Norwegian Public Health Institute and NOMA, Dr. Ranhoff and colleagues investigated the first 100 deaths among nursing-home residents who received the vaccine. The team consisted of three geriatricians and an infectious disease specialist who sees patients in nursing homes.

They looked at each patient’s clinical course before and after vaccination, their health trajectory and life expectancy at the time of vaccination, new symptoms following vaccination, and the time from vaccination to new symptoms and to death.

In addition, the investigators evaluated Clinical Frailty Scale (CFS) scores for each patient. CFS scores range from 1 (very fit) to 9 (terminally ill, with a life expectancy of less than 6 months who are otherwise evidently frail).

The initial investigation found that among 95 evaluable patients, the association between vaccination and death was “probable” in 10, “possible” in 26, and “unlikely” in 59.

The mean time from vaccination to symptoms was 1.4 days in the probable cases, 2.5 days in the possible cases, and 4.7 days in the unlikely cases.

The mean time from vaccination to death was 3.1, 8.3, and 8.2 days, respectively.

In all three categories, the patients had mean CFS scores ranging from 7.6 to 7.9, putting them in the “severely frail” category, defined as people who are completely dependent for personal care but seem stable and not at high risk for dying.

“We have quite many nursing home residents in Norway, 35,000; more than 80% have dementia, and the mean age is 85 years. We know that approximately 45 people die every day in these nursing homes, and their mean age of death is 87.5 years,” Dr. Ranhoff said.
 

Population-wide study

Dr. Ranhoff and colleagues also looked more broadly into the question of potential vaccine-related mortality in the total population of older people in Norway from the day of vaccination to follow-up at 3 weeks.

They conducted a matched cohort study to investigate the relationship between the mRNA SARS-CoV-2 vaccine and overall death among persons aged 65 and older in the general population, and across four groups: patients receiving home-based care, long-term nursing home patients, short-term nursing home patients, and those not receiving health services.

The researchers identified a total of 967,786 residents of Norway aged 65 and over at the start of the country’s vaccination campaign at the end of December, 2020, and they matched vaccinated individuals with unvaccinated persons based on demographic, geographic, and clinical risk group factors.

Dr. Ranhoff showed Kaplan-Meier survival curves for the total population and for each of the health-service states. In all cases there was a clear survival benefit for vaccinated vs. unvaccinated patients. She did not, however, provide specific numbers or hazard ratios for the differences between vaccinated and unvaccinated individuals in each of the comparisons.

The study was supported by the Norwegian Institute of Public Health. Dr. Ranhoff and Dr. Benetos reported no conflicts of interest.

Unless pneumonia is suspected, clinicians should not prescribe antibiotics for most children with chest infections, according to findings of the ARTIC-PC randomized controlled trial, published in The Lancet.

“Prescribing for children with uncomplicated chest infections is still common in most countries,” said lead author Paul Little, MD, professor of primary care research at the University of Southampton, England, in an interview.

But there are barriers to stopping this practice, he said. “If you prescribe an antibiotic and the child gets better, even if the antibiotic was not doing that much, the parents then think that it was the antibiotic that was responsible for the recovery and so expect antibiotics the next time. So, physician prescribing of antibiotics in effect medicalizes illness and keeps the cycle of expectations, reconsultations, and prescriptions going.”

The study included 432 children aged 6 months to 12 years (median age, 3.2 years) who presented at 56 general practices in England with acute, uncomplicated lower respiratory tract infection (LRTI) of less than 21 days’ duration and in whom pneumonia was not suspected clinically. The children were randomly assigned to undergo 7 days of treatment with either amoxicillin 50 mg/kg or placebo. The primary outcome was duration of symptoms rated moderately bad or worse.

For up to 4 weeks, parents scored symptoms – including cough, phlegm, shortness of breath, wheeze, blocked or runny nose, disturbed sleep, feeling generally unwell, fever, and interference with normal activities – in a daily diary. The secondary outcome was symptom severity. Prespecified analyses were made for key clinical subgroups of patients for whom clinicians commonly prescribe (those with chest signs, fever, physician rating of unwell, sputum or chest rattle, and shortness of breath).

There was no significant difference in outcome between children treated with antibiotics and those treated with placebo. The median duration of moderately bad or worse symptoms was similar between the antibiotics group and the placebo group (5 vs. 6 days; hazard ratio, 1.13), as was the median time until symptoms were rated absent or as causing very little problem (7 vs. 8 days; HR, 1.09). There was a small significant difference between the groups in symptom severity score on days 2-4 after seeing the doctor (1.8 in the antibiotics group vs. 2.1 in the placebo group), “which was equivalent to less than one child in three rating symptoms a slight problem rather than very little problem,” the study authors report. “The treatment effects for all outcomes were similar for most subgroups ... but the effect of antibiotics was slightly, but not significantly, greater among those with fever or those who were unwell,” they add.

The investigators conclude that “similar to adults, antibiotics are unlikely to make a clinically important difference to the symptom burden for uncomplicated lower respiratory tract infections in children – both overall, and for the key clinical subgroups where antibiotic prescribing is most common.” They recommend that clinicians provide “safety-netting advice” to parents, such as explaining what illness course to expect and when a return visit would be necessary.

The findings provide “more evidence to do less,” wrote Rianne Oostenbrink, MD, PhD, from Erasmus MC-Sophia, in Rotterdam, the Netherlands, and Lina Jankauskaite, MD, PhD, from Lithuanian University of Health Sciences, Kaunas, in an accompanying comment.

“Overtesting and overtreatment of children are especially prominent in infectious diseases, when fever or other symptoms such as cough can be unspecific and can be of viral or bacterial origin,” they write.

The commenters note that despite antibiotics, most children did have moderately bad or worse symptoms on day 3, and symptoms had improved in about 75% of children in both groups at day 14. “A notable finding of this study is that only a few children had moderately bad or worse symptoms by day 14, and antibiotics did not alleviate the symptoms compared with placebo. Additionally, this trial aligns with other studies that have shown that reducing antibiotic treatment for LRTI is not associated with prolonged morbidity or higher incidence of complications.”

The study was funded by the UK National Institute for Health Research. Dr. Little, Dr. Jankauskaite, and Dr. Oostenbrink have disclosed no relevant financial relationships.

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

Unless pneumonia is suspected, clinicians should not prescribe antibiotics for most children with chest infections, according to findings of the ARTIC-PC randomized controlled trial, published in The Lancet.

“Prescribing for children with uncomplicated chest infections is still common in most countries,” said lead author Paul Little, MD, professor of primary care research at the University of Southampton, England, in an interview.

But there are barriers to stopping this practice, he said. “If you prescribe an antibiotic and the child gets better, even if the antibiotic was not doing that much, the parents then think that it was the antibiotic that was responsible for the recovery and so expect antibiotics the next time. So, physician prescribing of antibiotics in effect medicalizes illness and keeps the cycle of expectations, reconsultations, and prescriptions going.”

The study included 432 children aged 6 months to 12 years (median age, 3.2 years) who presented at 56 general practices in England with acute, uncomplicated lower respiratory tract infection (LRTI) of less than 21 days’ duration and in whom pneumonia was not suspected clinically. The children were randomly assigned to undergo 7 days of treatment with either amoxicillin 50 mg/kg or placebo. The primary outcome was duration of symptoms rated moderately bad or worse.

For up to 4 weeks, parents scored symptoms – including cough, phlegm, shortness of breath, wheeze, blocked or runny nose, disturbed sleep, feeling generally unwell, fever, and interference with normal activities – in a daily diary. The secondary outcome was symptom severity. Prespecified analyses were made for key clinical subgroups of patients for whom clinicians commonly prescribe (those with chest signs, fever, physician rating of unwell, sputum or chest rattle, and shortness of breath).

There was no significant difference in outcome between children treated with antibiotics and those treated with placebo. The median duration of moderately bad or worse symptoms was similar between the antibiotics group and the placebo group (5 vs. 6 days; hazard ratio, 1.13), as was the median time until symptoms were rated absent or as causing very little problem (7 vs. 8 days; HR, 1.09). There was a small significant difference between the groups in symptom severity score on days 2-4 after seeing the doctor (1.8 in the antibiotics group vs. 2.1 in the placebo group), “which was equivalent to less than one child in three rating symptoms a slight problem rather than very little problem,” the study authors report. “The treatment effects for all outcomes were similar for most subgroups ... but the effect of antibiotics was slightly, but not significantly, greater among those with fever or those who were unwell,” they add.

The investigators conclude that “similar to adults, antibiotics are unlikely to make a clinically important difference to the symptom burden for uncomplicated lower respiratory tract infections in children – both overall, and for the key clinical subgroups where antibiotic prescribing is most common.” They recommend that clinicians provide “safety-netting advice” to parents, such as explaining what illness course to expect and when a return visit would be necessary.

The findings provide “more evidence to do less,” wrote Rianne Oostenbrink, MD, PhD, from Erasmus MC-Sophia, in Rotterdam, the Netherlands, and Lina Jankauskaite, MD, PhD, from Lithuanian University of Health Sciences, Kaunas, in an accompanying comment.

“Overtesting and overtreatment of children are especially prominent in infectious diseases, when fever or other symptoms such as cough can be unspecific and can be of viral or bacterial origin,” they write.

The commenters note that despite antibiotics, most children did have moderately bad or worse symptoms on day 3, and symptoms had improved in about 75% of children in both groups at day 14. “A notable finding of this study is that only a few children had moderately bad or worse symptoms by day 14, and antibiotics did not alleviate the symptoms compared with placebo. Additionally, this trial aligns with other studies that have shown that reducing antibiotic treatment for LRTI is not associated with prolonged morbidity or higher incidence of complications.”

The study was funded by the UK National Institute for Health Research. Dr. Little, Dr. Jankauskaite, and Dr. Oostenbrink have disclosed no relevant financial relationships.

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

Unless pneumonia is suspected, clinicians should not prescribe antibiotics for most children with chest infections, according to findings of the ARTIC-PC randomized controlled trial, published in The Lancet.

“Prescribing for children with uncomplicated chest infections is still common in most countries,” said lead author Paul Little, MD, professor of primary care research at the University of Southampton, England, in an interview.

But there are barriers to stopping this practice, he said. “If you prescribe an antibiotic and the child gets better, even if the antibiotic was not doing that much, the parents then think that it was the antibiotic that was responsible for the recovery and so expect antibiotics the next time. So, physician prescribing of antibiotics in effect medicalizes illness and keeps the cycle of expectations, reconsultations, and prescriptions going.”

The study included 432 children aged 6 months to 12 years (median age, 3.2 years) who presented at 56 general practices in England with acute, uncomplicated lower respiratory tract infection (LRTI) of less than 21 days’ duration and in whom pneumonia was not suspected clinically. The children were randomly assigned to undergo 7 days of treatment with either amoxicillin 50 mg/kg or placebo. The primary outcome was duration of symptoms rated moderately bad or worse.

For up to 4 weeks, parents scored symptoms – including cough, phlegm, shortness of breath, wheeze, blocked or runny nose, disturbed sleep, feeling generally unwell, fever, and interference with normal activities – in a daily diary. The secondary outcome was symptom severity. Prespecified analyses were made for key clinical subgroups of patients for whom clinicians commonly prescribe (those with chest signs, fever, physician rating of unwell, sputum or chest rattle, and shortness of breath).

There was no significant difference in outcome between children treated with antibiotics and those treated with placebo. The median duration of moderately bad or worse symptoms was similar between the antibiotics group and the placebo group (5 vs. 6 days; hazard ratio, 1.13), as was the median time until symptoms were rated absent or as causing very little problem (7 vs. 8 days; HR, 1.09). There was a small significant difference between the groups in symptom severity score on days 2-4 after seeing the doctor (1.8 in the antibiotics group vs. 2.1 in the placebo group), “which was equivalent to less than one child in three rating symptoms a slight problem rather than very little problem,” the study authors report. “The treatment effects for all outcomes were similar for most subgroups ... but the effect of antibiotics was slightly, but not significantly, greater among those with fever or those who were unwell,” they add.

The investigators conclude that “similar to adults, antibiotics are unlikely to make a clinically important difference to the symptom burden for uncomplicated lower respiratory tract infections in children – both overall, and for the key clinical subgroups where antibiotic prescribing is most common.” They recommend that clinicians provide “safety-netting advice” to parents, such as explaining what illness course to expect and when a return visit would be necessary.

The findings provide “more evidence to do less,” wrote Rianne Oostenbrink, MD, PhD, from Erasmus MC-Sophia, in Rotterdam, the Netherlands, and Lina Jankauskaite, MD, PhD, from Lithuanian University of Health Sciences, Kaunas, in an accompanying comment.

“Overtesting and overtreatment of children are especially prominent in infectious diseases, when fever or other symptoms such as cough can be unspecific and can be of viral or bacterial origin,” they write.

The commenters note that despite antibiotics, most children did have moderately bad or worse symptoms on day 3, and symptoms had improved in about 75% of children in both groups at day 14. “A notable finding of this study is that only a few children had moderately bad or worse symptoms by day 14, and antibiotics did not alleviate the symptoms compared with placebo. Additionally, this trial aligns with other studies that have shown that reducing antibiotic treatment for LRTI is not associated with prolonged morbidity or higher incidence of complications.”

The study was funded by the UK National Institute for Health Research. Dr. Little, Dr. Jankauskaite, and Dr. Oostenbrink have disclosed no relevant financial relationships.

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

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

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

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

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

In frail elderly adults with COVID-19 infections, treatment with omega-3 fatty acids may improve lipid responses and decrease levels of proinflammatory lipid mediators, results of a small randomized controlled trial suggest.

Results of the study, which included 22 patients with multiple comorbidities, were presented at the European Geriatric Medicine Society annual congress, a hybrid live and online meeting.

The patients, who had a median age of 81 years, were randomized to receive an intravenous infusion of an omega-3 polyunsaturated fatty acid (PUFA) emulsion containing 10 g of fish oil per 100 mL or a saline placebo.

Those who received the intravenous infusion had significant decreases from baseline to end of treatment in the neutrophil-to-lymphocyte ratio (NLR), indicating marked reductions in systemic inflammation.

In contrast, patients randomized to a saline placebo had no significant improvements in NLR, Magnus Bäck, MD, PhD, from the Karolinska Institute in Stockholm reported at the meeting.

“Our lipidomic analysis also showed that omega-3 treatment skewed the lipid response, with reduced levels of proinflammatory lipid mediators, and increased levels of proresolving mediators,” according to a late-breaking abstract, which Dr. Bäck presented during the session.

Omega-3 treatment was not significantly associated with reduction in either C-reactive protein (CRP) or the proinflammatory cytokine interleukin-6, however.
 

‘Eicosanoid storm’

In a review article published in January 2021 in the open-access journal Frontiers in Physiology, Dr. Bäck and colleagues outlined the rationale for their randomized trial.

“Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications,” they wrote. “In addition to the release of cytokines, referred to as cytokine release syndrome or ‘cytokine storm,’ increased proinflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an ‘eicosanoid storm,’ which contributes to the uncontrolled systemic inflammation.”

Omega-3 PUFA contains proresolving mediators that can limit inflammatory reactions, suggesting the possibility of an inflammation-resolving benefit in patients with COVID-19 without concerns about immunosuppression, the authors hypothesized.
 

Trial details

In the trial, COVID-Omega-F, they enrolled patients with a COVID-19 diagnosis requiring hospitalization. Patients with an allergy to fish oil or who had contraindications to intravenous PUFA administration (for example, risk for bleeding, shock, or emboli) were excluded.

Ten patients were randomly assigned to receive infusions of the omega-3 PUFA and 12 were assigned to receive infusions of the placebo, once daily for 5 days. The primary outcome measure was change in inflammatory biomarkers, including white blood cell counts, CRP, cytokines, and lipid mediators.

Baseline demographic and clinical characteristics were similar between the two study arms, with a median of about 7 days since the onset of symptoms, and 3.5 days since a diagnosis of COVID-19.

All patients had low lymphocyte responses reflected by a high NLR, a prognostic measure for worse outcomes in patients with COVID-19 infections, Dr. Bäck said.

Inflammation was moderate, with a CRP of 65 mg/L in the placebo group and 62 mg/L in the omega-3 group.

Seven patients in each study arm received concomitant corticoid treatment. Two patients in each arm died in hospital, but there were no serious treatment-related adverse events.
 

Inflammatory markers improve

As noted before, there was a significant decline in NLR from baseline among patients randomized to omega-3 (P = .02) but no corresponding decrease in patients assigned to placebo infusions.

“The significant decrease was largely driven by an increase in the lymphocyte count in the omega-3 treated group (P = .004), whereas lymphocytes did not significantly change,” Dr. Bäck said.

As expected, patients in the omega-3 group had pronounced increases in omega-3 fatty acids, including eicosapentaenoic acid and docosahexaenoic acid.

The metabolism of fatty acids also differed markedly between the groups, with a significant decrease in the omega-3 group but not the placebo group in proinflammatory mediators, and an increase in precursors to proresolving mediators, Dr. Bäck noted.
 

AFib concerns

In a question-and-answer part of the session, a physician who identified herself as “Senya from Russia” questioned the safety of omega-3 treatment in this population, “because recently there was a meta-analysis which showed that omega-3 fatty acids will increase the risk of atrial fibrillation in older adults especially.”

The systematic review and meta-analysis she referred to, published in Circulation and reported on by this news organization, showed that, among 81,210 patients with a mean age of 65 enrolled in seven randomized controlled trials, omega-3 fatty acid supplementation was associated with a 25% increase in risk for atrial fibrillation. This risk appeared to be higher in trials testing doses greater than 1 g/day, according to the paper.

“This was not monitored in this study,” Dr. Bäck replied. “It is true that the meta-analysis showed an increased incidence of atrial fibrillation, so it would be something to monitor in case this trial would be expanded to a larger population.”

The study was supported by the Karolinska Institute. Dr. Bäck disclosed no relevant financial relationships.

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

The United States just passed the 6-million mark in COVID-19 cases among children, with the last million cases taking less time to record than any of the first five, according to new data from the American Academy of Pediatrics and the Children’s Hospital Association.

The five-millionth case was reported during the week of Aug. 27 to Sept. 2, and case number 6 million came during the week of Oct. 1-7, just 5 weeks later, compared with the 6 weeks it took to go from 1 million to 2 million last November and December, the AAP and CHA said in their weekly COVID-19 report.

There were 148,222 new cases reported during the week ending Oct. 7, bringing the total case count to 6,047,371 since the pandemic started. New cases continued to drop, however, and that weekly count was down by 14.6% from the previous week and by 41.1% from the peak of almost 252,000 reached in early September, the two groups said while also noting limitations to the data, such as three states (Alabama, Nebraska, and Texas) that are no longer updating their COVID-19 dashboards.

Other metrics show similar drops in recent weeks. Among children aged 0-11 years, emergency department visits involving a COVID-19 diagnosis dropped from 4.1% of all ED visits in late August to 1.4% of ED visits on Oct. 6. ED visits with a COVID-19 diagnosis fell from a peak of 8.5% on Aug. 22 to 1.5% on Oct. 6 for 12- to 15-year-olds and from 8.5% to 1.5% in those aged 16-17 years, according to data from the Centers for Disease Control and Prevention.

The rate of new hospital admissions for children aged 0-17 years was down to 0.26 per 100,000 population on Oct. 9 after reaching 0.51 per 100,000 on Sept. 4. Hospitalizations in children totaled just over 64,000 from Aug. 1, 2020, to Oct. 9, 2021, which is just over 2% of all COVID-19–related admissions over that time period, the CDC said on its COVID Data Tracker.

That pattern, unfortunately, also applies to vaccinations. “The number of children receiving their first COVID-19 vaccine this week [Sept. 30 to Oct. 6], about 156,000, was the lowest number since vaccines were available,” the AAP said in a separate report on vaccination trends, adding that “the number of children receiving their first dose has steadily declined from 8 weeks ago when 586,000 children received their initial dose the week ending Aug. 11.”

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The United States just passed the 6-million mark in COVID-19 cases among children, with the last million cases taking less time to record than any of the first five, according to new data from the American Academy of Pediatrics and the Children’s Hospital Association.

The five-millionth case was reported during the week of Aug. 27 to Sept. 2, and case number 6 million came during the week of Oct. 1-7, just 5 weeks later, compared with the 6 weeks it took to go from 1 million to 2 million last November and December, the AAP and CHA said in their weekly COVID-19 report.

There were 148,222 new cases reported during the week ending Oct. 7, bringing the total case count to 6,047,371 since the pandemic started. New cases continued to drop, however, and that weekly count was down by 14.6% from the previous week and by 41.1% from the peak of almost 252,000 reached in early September, the two groups said while also noting limitations to the data, such as three states (Alabama, Nebraska, and Texas) that are no longer updating their COVID-19 dashboards.

Other metrics show similar drops in recent weeks. Among children aged 0-11 years, emergency department visits involving a COVID-19 diagnosis dropped from 4.1% of all ED visits in late August to 1.4% of ED visits on Oct. 6. ED visits with a COVID-19 diagnosis fell from a peak of 8.5% on Aug. 22 to 1.5% on Oct. 6 for 12- to 15-year-olds and from 8.5% to 1.5% in those aged 16-17 years, according to data from the Centers for Disease Control and Prevention.

The rate of new hospital admissions for children aged 0-17 years was down to 0.26 per 100,000 population on Oct. 9 after reaching 0.51 per 100,000 on Sept. 4. Hospitalizations in children totaled just over 64,000 from Aug. 1, 2020, to Oct. 9, 2021, which is just over 2% of all COVID-19–related admissions over that time period, the CDC said on its COVID Data Tracker.

That pattern, unfortunately, also applies to vaccinations. “The number of children receiving their first COVID-19 vaccine this week [Sept. 30 to Oct. 6], about 156,000, was the lowest number since vaccines were available,” the AAP said in a separate report on vaccination trends, adding that “the number of children receiving their first dose has steadily declined from 8 weeks ago when 586,000 children received their initial dose the week ending Aug. 11.”

[email protected]

The United States just passed the 6-million mark in COVID-19 cases among children, with the last million cases taking less time to record than any of the first five, according to new data from the American Academy of Pediatrics and the Children’s Hospital Association.

The five-millionth case was reported during the week of Aug. 27 to Sept. 2, and case number 6 million came during the week of Oct. 1-7, just 5 weeks later, compared with the 6 weeks it took to go from 1 million to 2 million last November and December, the AAP and CHA said in their weekly COVID-19 report.

There were 148,222 new cases reported during the week ending Oct. 7, bringing the total case count to 6,047,371 since the pandemic started. New cases continued to drop, however, and that weekly count was down by 14.6% from the previous week and by 41.1% from the peak of almost 252,000 reached in early September, the two groups said while also noting limitations to the data, such as three states (Alabama, Nebraska, and Texas) that are no longer updating their COVID-19 dashboards.

Other metrics show similar drops in recent weeks. Among children aged 0-11 years, emergency department visits involving a COVID-19 diagnosis dropped from 4.1% of all ED visits in late August to 1.4% of ED visits on Oct. 6. ED visits with a COVID-19 diagnosis fell from a peak of 8.5% on Aug. 22 to 1.5% on Oct. 6 for 12- to 15-year-olds and from 8.5% to 1.5% in those aged 16-17 years, according to data from the Centers for Disease Control and Prevention.

The rate of new hospital admissions for children aged 0-17 years was down to 0.26 per 100,000 population on Oct. 9 after reaching 0.51 per 100,000 on Sept. 4. Hospitalizations in children totaled just over 64,000 from Aug. 1, 2020, to Oct. 9, 2021, which is just over 2% of all COVID-19–related admissions over that time period, the CDC said on its COVID Data Tracker.

That pattern, unfortunately, also applies to vaccinations. “The number of children receiving their first COVID-19 vaccine this week [Sept. 30 to Oct. 6], about 156,000, was the lowest number since vaccines were available,” the AAP said in a separate report on vaccination trends, adding that “the number of children receiving their first dose has steadily declined from 8 weeks ago when 586,000 children received their initial dose the week ending Aug. 11.”

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Practice Gap

The Sarcoptes scabiei mite is a microscopic organism that causes scabies in the human host. The scabies mite is highly transmissible, making scabies a common disease in heavily populated areas. The mite survives by burrowing into the epidermis, where it feeds, lays eggs, and defecates.¹

The rash in the host represents an allergic reaction to the body of the scabies mite, producing symptoms such as intense itching, rash, and erosions of the skin. The scabies rash tends to occur in warm and occluded areas of the body such as the hands, axillae, groin, buttocks, and feet.^1,2

Delaying treatment of scabies can be hazardous because of the risk of rapid spread from one person to another. This rapid spread can be debilitating in specific populations, such as the immunocompromised, elderly, and disabled.

Mineral oil preparation is the classic method used to identify scabies (Figure 1). This method relies on obtaining mites by applying mineral oil to the skin and using a 15-mm blade to scrape off layers of the affected skin. The scraped material is spread onto a microscope slide with mineral oil, a coverslip is applied, and the specimen is analyzed by direct microscopy. This method proves only as effective as knowing where the few mites are located.

At any time, only 10 to 12 mites live on a human host.³ Therefore, it can be challenging to obtain a mite for diagnosis because the location of the skin mites may be unknown. Dermoscopy can be used to locate burrows and other signs of S scabiei. With a dermatoscope, the scabies mite can be identified by the so-called delta-wing jet sign.⁴

However, dermoscopy is not always successful because extensive hemorrhagic crusting and erosions of the skin secondary to constant scratching can obscure the appearance of burrows and mites. Because patients are constantly scratching areas of irritation, it is possible that S scabiei can be located under the fingernail of the dominant hand.

The Technique

To address this practice gap, a mineral oil scabies preparation can be performed by scraping under the fingernail plate at the level of the hyponychium. Mites might accumulate underneath the fingernails of the dominant hand when patients scratch the area of the skin where S scabiei mites are burrowing and reproducing.

A convenient and painless way to obtain a mineral oil scabies preparation from under the fingernail is to use the tip of a disposable hyfrecator, readily available in most dermatology practices for use in electrosurgery (Figure 2). Using the blunt end of the hyfrecator tip for the mineral oil preparation would be done without attachment to the full apparatus.

The hyponychium of the fingernail is prepared with mineral oil, which aids in collecting and suspending the material obtained from under the nail plate. Using the blunt end of the hyfrecator tip, material from underneath the fingernail is removed using a gentle sweeping motion (Figure 3). The specimen is then analyzed under the microscope similar to a routine mineral oil scabies preparation. This method can be utilized by health care providers for easy and painless diagnosis of scabies.

Practice Implications

Use of a blunt hyfrecator tip to extract S scabiei from underneath the fingernail plate can be used for efficient diagnosis of scabies. This technique can be implemented in any clinic where blunt-tip hyfrecator electrodes are available. Using a gentle sweeping motion, the blunt-tip hyfrecator allows the provider to extract material from under the fingernail for diagnosis. The material obtained is used to prepare a mineral oil scabies preparation for direct microscopic analysis.

This technique can diagnose scabies efficiently, and treatment can be initiated promptly. Use of a disposable blunt-tip hyfrecator for scabies extraction is a novel technique that can be added to the armamentarium of tools to diagnose scabies, which includes traditional mineral oil preparation and dermoscopy.

Practice Gap

The Sarcoptes scabiei mite is a microscopic organism that causes scabies in the human host. The scabies mite is highly transmissible, making scabies a common disease in heavily populated areas. The mite survives by burrowing into the epidermis, where it feeds, lays eggs, and defecates.¹

The rash in the host represents an allergic reaction to the body of the scabies mite, producing symptoms such as intense itching, rash, and erosions of the skin. The scabies rash tends to occur in warm and occluded areas of the body such as the hands, axillae, groin, buttocks, and feet.^1,2

Delaying treatment of scabies can be hazardous because of the risk of rapid spread from one person to another. This rapid spread can be debilitating in specific populations, such as the immunocompromised, elderly, and disabled.

Mineral oil preparation is the classic method used to identify scabies (Figure 1). This method relies on obtaining mites by applying mineral oil to the skin and using a 15-mm blade to scrape off layers of the affected skin. The scraped material is spread onto a microscope slide with mineral oil, a coverslip is applied, and the specimen is analyzed by direct microscopy. This method proves only as effective as knowing where the few mites are located.

At any time, only 10 to 12 mites live on a human host.³ Therefore, it can be challenging to obtain a mite for diagnosis because the location of the skin mites may be unknown. Dermoscopy can be used to locate burrows and other signs of S scabiei. With a dermatoscope, the scabies mite can be identified by the so-called delta-wing jet sign.⁴

However, dermoscopy is not always successful because extensive hemorrhagic crusting and erosions of the skin secondary to constant scratching can obscure the appearance of burrows and mites. Because patients are constantly scratching areas of irritation, it is possible that S scabiei can be located under the fingernail of the dominant hand.

The Technique

To address this practice gap, a mineral oil scabies preparation can be performed by scraping under the fingernail plate at the level of the hyponychium. Mites might accumulate underneath the fingernails of the dominant hand when patients scratch the area of the skin where S scabiei mites are burrowing and reproducing.

A convenient and painless way to obtain a mineral oil scabies preparation from under the fingernail is to use the tip of a disposable hyfrecator, readily available in most dermatology practices for use in electrosurgery (Figure 2). Using the blunt end of the hyfrecator tip for the mineral oil preparation would be done without attachment to the full apparatus.

The hyponychium of the fingernail is prepared with mineral oil, which aids in collecting and suspending the material obtained from under the nail plate. Using the blunt end of the hyfrecator tip, material from underneath the fingernail is removed using a gentle sweeping motion (Figure 3). The specimen is then analyzed under the microscope similar to a routine mineral oil scabies preparation. This method can be utilized by health care providers for easy and painless diagnosis of scabies.

Practice Implications

Use of a blunt hyfrecator tip to extract S scabiei from underneath the fingernail plate can be used for efficient diagnosis of scabies. This technique can be implemented in any clinic where blunt-tip hyfrecator electrodes are available. Using a gentle sweeping motion, the blunt-tip hyfrecator allows the provider to extract material from under the fingernail for diagnosis. The material obtained is used to prepare a mineral oil scabies preparation for direct microscopic analysis.

This technique can diagnose scabies efficiently, and treatment can be initiated promptly. Use of a disposable blunt-tip hyfrecator for scabies extraction is a novel technique that can be added to the armamentarium of tools to diagnose scabies, which includes traditional mineral oil preparation and dermoscopy.

Practice Gap

The Sarcoptes scabiei mite is a microscopic organism that causes scabies in the human host. The scabies mite is highly transmissible, making scabies a common disease in heavily populated areas. The mite survives by burrowing into the epidermis, where it feeds, lays eggs, and defecates.¹

The rash in the host represents an allergic reaction to the body of the scabies mite, producing symptoms such as intense itching, rash, and erosions of the skin. The scabies rash tends to occur in warm and occluded areas of the body such as the hands, axillae, groin, buttocks, and feet.^1,2

Delaying treatment of scabies can be hazardous because of the risk of rapid spread from one person to another. This rapid spread can be debilitating in specific populations, such as the immunocompromised, elderly, and disabled.

Mineral oil preparation is the classic method used to identify scabies (Figure 1). This method relies on obtaining mites by applying mineral oil to the skin and using a 15-mm blade to scrape off layers of the affected skin. The scraped material is spread onto a microscope slide with mineral oil, a coverslip is applied, and the specimen is analyzed by direct microscopy. This method proves only as effective as knowing where the few mites are located.

At any time, only 10 to 12 mites live on a human host.³ Therefore, it can be challenging to obtain a mite for diagnosis because the location of the skin mites may be unknown. Dermoscopy can be used to locate burrows and other signs of S scabiei. With a dermatoscope, the scabies mite can be identified by the so-called delta-wing jet sign.⁴

However, dermoscopy is not always successful because extensive hemorrhagic crusting and erosions of the skin secondary to constant scratching can obscure the appearance of burrows and mites. Because patients are constantly scratching areas of irritation, it is possible that S scabiei can be located under the fingernail of the dominant hand.

The Technique

To address this practice gap, a mineral oil scabies preparation can be performed by scraping under the fingernail plate at the level of the hyponychium. Mites might accumulate underneath the fingernails of the dominant hand when patients scratch the area of the skin where S scabiei mites are burrowing and reproducing.

A convenient and painless way to obtain a mineral oil scabies preparation from under the fingernail is to use the tip of a disposable hyfrecator, readily available in most dermatology practices for use in electrosurgery (Figure 2). Using the blunt end of the hyfrecator tip for the mineral oil preparation would be done without attachment to the full apparatus.

The hyponychium of the fingernail is prepared with mineral oil, which aids in collecting and suspending the material obtained from under the nail plate. Using the blunt end of the hyfrecator tip, material from underneath the fingernail is removed using a gentle sweeping motion (Figure 3). The specimen is then analyzed under the microscope similar to a routine mineral oil scabies preparation. This method can be utilized by health care providers for easy and painless diagnosis of scabies.

Practice Implications

Use of a blunt hyfrecator tip to extract S scabiei from underneath the fingernail plate can be used for efficient diagnosis of scabies. This technique can be implemented in any clinic where blunt-tip hyfrecator electrodes are available. Using a gentle sweeping motion, the blunt-tip hyfrecator allows the provider to extract material from under the fingernail for diagnosis. The material obtained is used to prepare a mineral oil scabies preparation for direct microscopic analysis.

This technique can diagnose scabies efficiently, and treatment can be initiated promptly. Use of a disposable blunt-tip hyfrecator for scabies extraction is a novel technique that can be added to the armamentarium of tools to diagnose scabies, which includes traditional mineral oil preparation and dermoscopy.

More than half a million individuals are without housing (NWH) on any given night in the United States, as estimated by the US Department of Housing and Urban Development. ¹ Lack of hygiene, increased risk of infection and infestation due to living conditions, and barriers to health care put these individuals at increased risk for disease. ² Skin disease, including fungal infection and acne, are within the top 10 most prevalent diseases worldwide and can cause major psychologic impairment, yet dermatologic concerns and clinical outcomes in NWH patients have not been well characterized. ^2-5 Further, because this vulnerable demographic tends to be underinsured, they frequently present to the emergency department (ED) for management of disease. ^1,6 Survey of common concerns in NWH patients is of utility to consulting dermatologists and nondermatologist providers in the ED, who can familiarize themselves with management of diseases they are more likely to encounter. Few studies examine dermatologic conditions in the ED, and a thorough literature review indicates none have included homelessness as a variable. ^6,7 Additionally, comparison with a matched control group of patients with housing (WH) is limited. ^5,8 We present one of the largest comparisons of cutaneous disease in NWH vs WH patients in a single hospital system to elucidate the types of cutaneous disease that motivate patients to seek care, the location of skin disease, and differences in clinical care.

Methods

A retrospective medical record review of patients seen for an inclusive list of dermatologic diagnoses in the ED or while admitted at University Medical Center New Orleans, Louisiana (UMC), between January 1, 2018, and April 21, 2020, was conducted. This study was qualified as exempt from the institutional review board by Louisiana State University because it proposed zero risk to the patients and remained completely anonymous. Eight hundred forty-two total medical records were reviewed (NWH, 421; WH, 421)(Table 1). Patients with housing were matched based on self-identified race and ethnicity, sex, and age. Disease categories were constructed based on fundamental pathophysiology adapted from Dermatology⁹: infectious, noninfectious inflammatory, neoplasm, trauma and wounds, drug-related eruptions, vascular, pruritic, pigmented, bullous, neuropsychiatric, and other. Other included unspecified eruptions as well as miscellaneous lesions such as calluses. The current chief concern, anatomic location, and configuration were recorded, as well as biopsied lesions and outpatient referrals or inpatient consultations to dermatology or other specialties, including wound care, infectious disease, podiatry, and surgery. χ² analysis was used to analyze significance of cutaneous categories, body location, and referrals. Groups smaller than 5 defaulted to the Fisher exact test.

Results

The total diagnoses (including both chief concerns and secondary diagnoses) are shown in Table 2. Chief concerns were more frequently cutaneous or dermatologic for WH (NWH, 209; WH, 307; P<.001). In both groups, cutaneous infectious etiologies were more likely to be a patient’s presenting chief concern (58% NWH, P=.002; 42% WH, P<.001). Noninfectious inflammatory etiologies and pigmented lesions were more likely to be secondary diagnoses with an unrelated noncutaneous concern; noninfectious inflammatory etiologies were only 16% of the total cutaneous chief concerns (11% NWH, P=.04; 20% WH, P=.03), and no pigmented lesions were chief concerns.

Infection was the most common chief concern, though NWH patients presented with significantly more infectious concerns (NWH, 212; WH, 150; P<.001), particularly infestations (NWH, 33; WH, 8; P<.001) and bacterial etiologies (NWH, 127; WH, 100; P=.04). The majority of bacterial etiologies were either an abscess or cellulitis (NWH, 106; WH, 83), though infected chronic wounds were categorized as bacterial infection when treated definitively as such (eg, in the case of sacral ulcers causing osteomyelitis)(NWH, 21; WH, 17). Of note, infectious etiology was associated with intravenous drug use (IVDU) in both NWH and WH patients. Of 184 NWH who reported IVDU, 127 had an infectious diagnosis (P<.001). Similarly, 43 of 56 total WH patients who reported IVDU had an infectious diagnosis (P<.001). Infestation (within the infectious category) included scabies (NWH, 20; WH, 3) and insect or arthropod bites (NWH, 12; WH, 5). Two NWH patients also presented with swelling of the lower extremities and were subsequently diagnosed with maggot infestations. Fungal and viral etiologies were not significantly increased in either group; however, NWH did have a higher incidence of tinea pedis (NWH, 14; WH, 4; P=.03).

More neoplasms (NWH, 6; WH, 16; P=.03), noninfectious inflammatory eruptions (NWH, 48; WH, 85; P<.001), and cutaneous drug eruptions (NWH, 5; WH, 27; P<.001) were reported in WH patients. There was no significant difference in benign vs malignant neoplastic processes between groups. More noninfectious inflammatory eruptions in WH were specifically driven by a markedly increased incidence of follicular (NWH, 9; WH, 29; P<.001) and urticarial/erythematous (NWH, 3; WH, 13; P=.02) lesions. Follicular etiologies included acne (NWH, 1; WH, 6; P=.12), folliculitis (NWH, 5; WH, 2; P=.45), hidradenitis suppurativa (NWH, 2; WH, 11; P=.02), and pilonidal and sebaceous cysts (NWH, 1; WH, 10; P=.01). Allergic urticaria dominated the urticarial/erythematous category (NWH, 3; WH, 11; P=.06), though there were 2 WH presentations of diffuse erythema and skin peeling.

Another substantial proportion of cutaneous etiologies were due to trauma or chronic wounds. Significantly more traumatic injuries presented in NWH patients vs WH patients (36 vs 31; P=.04). Trauma included human or dog bites (NWH, 5; WH, 4), sunburns (NWH, 3; WH, 0), other burns (NWH, 11; WH, 13), abrasions and lacerations (NWH, 16; WH, 3; P=.004), and foreign bodies (NWH, 1; WH, 1). Wounds consisted of chronic wounds such as those due to diabetes mellitus (foot ulcers) or immobility (sacral ulcers); numbers were similar between groups.

Looking at location, NWH patients had more pathology on the feet (NWH, 62; WH, 39; P=.02), whereas WH patients had more disseminated multiregional concerns (NWH, 55; WH, 75; P=.05). No one body location was notably more likely to warrant a chief concern.

For clinical outcomes, more WH patients received a consultation of any kind (NWH, 171; WH, 217; P<.001), consultation to dermatology (NWH, 49; WH, 87; P<.001), and consultation to surgery (NWH, 64; WH, 110; P<.001)(Table 3 and Figure). More outpatient referrals to dermatology were made for WH patients (NWH, 61; WH, 82; P=.05). Notably, NWH patients presented for 80% fewer hospital follow-up appointments (NWH, 11; WH, 55; P<.001). It is essential to note that these findings were not affected by self-reported race or ethnicity. Results remained significant when broken into cohorts consisting of patients with and without skin of color.

Comment

Cutaneous Concerns in NWH Patients—Although cutaneous disease has been reported to disproportionately affect NWH patients,¹⁰ in our cohort, NWH patients had fewer cutaneous chief concerns than WH patients. However, without comparing with all patients entering the ED at UMC, we cannot make a statement on this claim. We do present a few reasons why NWH patients do not have more cutaneous concerns. First, they may wait to present with cutaneous disease until it becomes more severe (eg, until chronic wounds have progressed to infections). Second, as discussed in depth by Hollestein and Nijsten,³ dermatologic disease may be a major contributor to the overall count of disability-adjusted life years but may play a minor role in individual disability. Therefore, skin disease often is considered less important on an individual basis, despite substantial psychosocial burden, leading to further stigmatization of this vulnerable population and discouraged care-seeking behavior, particularly for noninfectious inflammatory eruptions, which were notably more present in WH individuals. Third, fewer dermatologic lesions were reported on NWH patients, which may explain why all 3 WH pigmented lesions were diagnosed after presentation with a noncutaneous concern (eg, headache, anemia, nausea).

Infectious Cutaneous Diagnoses—The increased presentation of infectious etiologies, especially bacterial, is linked to the increased numbers of IVDUs reported in NWH individuals as well as increased exposure and decreased access to basic hygienic supplies. Intravenous drug use acted as an effect modifier of infectious etiology diagnoses, playing a major role in both NWH and WH cohorts. Although Black and Hispanic individuals as well as individuals with low socioeconomic status have increased proportions of skin cancer, there are inadequate data on the prevalence in NWH individuals.⁴ We found no increase in malignant dermatologic processes in NWH individuals; however, this may be secondary to inadequate screening with a total body skin examination.

Clinical Workup of NWH Patients—Because most NWH individuals present to the ED to receive care, their care compared with WH patients should be considered. In this cohort, WH patients received a less extensive clinical workup. They received almost half as many dermatologic consultations and fewer outpatient referrals to dermatology. Major communication barriers may affect NWH presentation to follow-up, which was drastically lower than WH individuals, as scheduling typically occurs well after discharge from the ED or inpatient unit. We suggest a few alterations to improve dermatologic care for NWH individuals:

• Consider inpatient consultation for serious dermatologic conditions—even if chronic—to improve disease control, considering that many barriers inhibit follow-up in clinic.

• Involve outreach teams, such as the Assertive Community Treatment teams, that assist individuals by delivering medicine for psychiatric disorders, conducting total-body skin examinations, assisting with wound care, providing basic skin barrier creams or medicaments, and carrying information regarding outpatient follow-up.

• Educate ED providers on the most common skin concerns, especially those that fall within the noninfectious inflammatory category, such as hidradenitis suppurativa, which could easily be misdiagnosed as an abscess.

Future Directions—Owing to limitations of a retrospective cohort study, we present several opportunities for further research on this vulnerable population. The severity of disease, especially infectious etiologies, should be graded to determine if NWH patients truly present later in the disease course. The duration and quality of housing for NWH patients could be categorized based on living conditions (eg, on the street vs in a shelter). Although the findings of our NWH cohort presenting to the ED at UMC provide helpful insight into dermatologic disease, these findings may be disparate from those conducted at other locations in the United States. University Medical Center provides care to mostly subsidized insurance plans in a racially diverse community. Improved outcomes for the NWH individuals living in New Orleans start with obtaining a greater understanding of their diseases and where disparities exist that can be bridged with better care.

Acknowledgment—The dataset generated during this study and used for analysis is not publicly available to protect public health information but is available from the corresponding author on reasonable request.

More than half a million individuals are without housing (NWH) on any given night in the United States, as estimated by the US Department of Housing and Urban Development. ¹ Lack of hygiene, increased risk of infection and infestation due to living conditions, and barriers to health care put these individuals at increased risk for disease. ² Skin disease, including fungal infection and acne, are within the top 10 most prevalent diseases worldwide and can cause major psychologic impairment, yet dermatologic concerns and clinical outcomes in NWH patients have not been well characterized. ^2-5 Further, because this vulnerable demographic tends to be underinsured, they frequently present to the emergency department (ED) for management of disease. ^1,6 Survey of common concerns in NWH patients is of utility to consulting dermatologists and nondermatologist providers in the ED, who can familiarize themselves with management of diseases they are more likely to encounter. Few studies examine dermatologic conditions in the ED, and a thorough literature review indicates none have included homelessness as a variable. ^6,7 Additionally, comparison with a matched control group of patients with housing (WH) is limited. ^5,8 We present one of the largest comparisons of cutaneous disease in NWH vs WH patients in a single hospital system to elucidate the types of cutaneous disease that motivate patients to seek care, the location of skin disease, and differences in clinical care.

Methods

A retrospective medical record review of patients seen for an inclusive list of dermatologic diagnoses in the ED or while admitted at University Medical Center New Orleans, Louisiana (UMC), between January 1, 2018, and April 21, 2020, was conducted. This study was qualified as exempt from the institutional review board by Louisiana State University because it proposed zero risk to the patients and remained completely anonymous. Eight hundred forty-two total medical records were reviewed (NWH, 421; WH, 421)(Table 1). Patients with housing were matched based on self-identified race and ethnicity, sex, and age. Disease categories were constructed based on fundamental pathophysiology adapted from Dermatology⁹: infectious, noninfectious inflammatory, neoplasm, trauma and wounds, drug-related eruptions, vascular, pruritic, pigmented, bullous, neuropsychiatric, and other. Other included unspecified eruptions as well as miscellaneous lesions such as calluses. The current chief concern, anatomic location, and configuration were recorded, as well as biopsied lesions and outpatient referrals or inpatient consultations to dermatology or other specialties, including wound care, infectious disease, podiatry, and surgery. χ² analysis was used to analyze significance of cutaneous categories, body location, and referrals. Groups smaller than 5 defaulted to the Fisher exact test.

Results

The total diagnoses (including both chief concerns and secondary diagnoses) are shown in Table 2. Chief concerns were more frequently cutaneous or dermatologic for WH (NWH, 209; WH, 307; P<.001). In both groups, cutaneous infectious etiologies were more likely to be a patient’s presenting chief concern (58% NWH, P=.002; 42% WH, P<.001). Noninfectious inflammatory etiologies and pigmented lesions were more likely to be secondary diagnoses with an unrelated noncutaneous concern; noninfectious inflammatory etiologies were only 16% of the total cutaneous chief concerns (11% NWH, P=.04; 20% WH, P=.03), and no pigmented lesions were chief concerns.

Infection was the most common chief concern, though NWH patients presented with significantly more infectious concerns (NWH, 212; WH, 150; P<.001), particularly infestations (NWH, 33; WH, 8; P<.001) and bacterial etiologies (NWH, 127; WH, 100; P=.04). The majority of bacterial etiologies were either an abscess or cellulitis (NWH, 106; WH, 83), though infected chronic wounds were categorized as bacterial infection when treated definitively as such (eg, in the case of sacral ulcers causing osteomyelitis)(NWH, 21; WH, 17). Of note, infectious etiology was associated with intravenous drug use (IVDU) in both NWH and WH patients. Of 184 NWH who reported IVDU, 127 had an infectious diagnosis (P<.001). Similarly, 43 of 56 total WH patients who reported IVDU had an infectious diagnosis (P<.001). Infestation (within the infectious category) included scabies (NWH, 20; WH, 3) and insect or arthropod bites (NWH, 12; WH, 5). Two NWH patients also presented with swelling of the lower extremities and were subsequently diagnosed with maggot infestations. Fungal and viral etiologies were not significantly increased in either group; however, NWH did have a higher incidence of tinea pedis (NWH, 14; WH, 4; P=.03).

More neoplasms (NWH, 6; WH, 16; P=.03), noninfectious inflammatory eruptions (NWH, 48; WH, 85; P<.001), and cutaneous drug eruptions (NWH, 5; WH, 27; P<.001) were reported in WH patients. There was no significant difference in benign vs malignant neoplastic processes between groups. More noninfectious inflammatory eruptions in WH were specifically driven by a markedly increased incidence of follicular (NWH, 9; WH, 29; P<.001) and urticarial/erythematous (NWH, 3; WH, 13; P=.02) lesions. Follicular etiologies included acne (NWH, 1; WH, 6; P=.12), folliculitis (NWH, 5; WH, 2; P=.45), hidradenitis suppurativa (NWH, 2; WH, 11; P=.02), and pilonidal and sebaceous cysts (NWH, 1; WH, 10; P=.01). Allergic urticaria dominated the urticarial/erythematous category (NWH, 3; WH, 11; P=.06), though there were 2 WH presentations of diffuse erythema and skin peeling.

Another substantial proportion of cutaneous etiologies were due to trauma or chronic wounds. Significantly more traumatic injuries presented in NWH patients vs WH patients (36 vs 31; P=.04). Trauma included human or dog bites (NWH, 5; WH, 4), sunburns (NWH, 3; WH, 0), other burns (NWH, 11; WH, 13), abrasions and lacerations (NWH, 16; WH, 3; P=.004), and foreign bodies (NWH, 1; WH, 1). Wounds consisted of chronic wounds such as those due to diabetes mellitus (foot ulcers) or immobility (sacral ulcers); numbers were similar between groups.

Looking at location, NWH patients had more pathology on the feet (NWH, 62; WH, 39; P=.02), whereas WH patients had more disseminated multiregional concerns (NWH, 55; WH, 75; P=.05). No one body location was notably more likely to warrant a chief concern.

For clinical outcomes, more WH patients received a consultation of any kind (NWH, 171; WH, 217; P<.001), consultation to dermatology (NWH, 49; WH, 87; P<.001), and consultation to surgery (NWH, 64; WH, 110; P<.001)(Table 3 and Figure). More outpatient referrals to dermatology were made for WH patients (NWH, 61; WH, 82; P=.05). Notably, NWH patients presented for 80% fewer hospital follow-up appointments (NWH, 11; WH, 55; P<.001). It is essential to note that these findings were not affected by self-reported race or ethnicity. Results remained significant when broken into cohorts consisting of patients with and without skin of color.

Comment

Cutaneous Concerns in NWH Patients—Although cutaneous disease has been reported to disproportionately affect NWH patients,¹⁰ in our cohort, NWH patients had fewer cutaneous chief concerns than WH patients. However, without comparing with all patients entering the ED at UMC, we cannot make a statement on this claim. We do present a few reasons why NWH patients do not have more cutaneous concerns. First, they may wait to present with cutaneous disease until it becomes more severe (eg, until chronic wounds have progressed to infections). Second, as discussed in depth by Hollestein and Nijsten,³ dermatologic disease may be a major contributor to the overall count of disability-adjusted life years but may play a minor role in individual disability. Therefore, skin disease often is considered less important on an individual basis, despite substantial psychosocial burden, leading to further stigmatization of this vulnerable population and discouraged care-seeking behavior, particularly for noninfectious inflammatory eruptions, which were notably more present in WH individuals. Third, fewer dermatologic lesions were reported on NWH patients, which may explain why all 3 WH pigmented lesions were diagnosed after presentation with a noncutaneous concern (eg, headache, anemia, nausea).

Infectious Cutaneous Diagnoses—The increased presentation of infectious etiologies, especially bacterial, is linked to the increased numbers of IVDUs reported in NWH individuals as well as increased exposure and decreased access to basic hygienic supplies. Intravenous drug use acted as an effect modifier of infectious etiology diagnoses, playing a major role in both NWH and WH cohorts. Although Black and Hispanic individuals as well as individuals with low socioeconomic status have increased proportions of skin cancer, there are inadequate data on the prevalence in NWH individuals.⁴ We found no increase in malignant dermatologic processes in NWH individuals; however, this may be secondary to inadequate screening with a total body skin examination.

Clinical Workup of NWH Patients—Because most NWH individuals present to the ED to receive care, their care compared with WH patients should be considered. In this cohort, WH patients received a less extensive clinical workup. They received almost half as many dermatologic consultations and fewer outpatient referrals to dermatology. Major communication barriers may affect NWH presentation to follow-up, which was drastically lower than WH individuals, as scheduling typically occurs well after discharge from the ED or inpatient unit. We suggest a few alterations to improve dermatologic care for NWH individuals:

• Consider inpatient consultation for serious dermatologic conditions—even if chronic—to improve disease control, considering that many barriers inhibit follow-up in clinic.

• Involve outreach teams, such as the Assertive Community Treatment teams, that assist individuals by delivering medicine for psychiatric disorders, conducting total-body skin examinations, assisting with wound care, providing basic skin barrier creams or medicaments, and carrying information regarding outpatient follow-up.

• Educate ED providers on the most common skin concerns, especially those that fall within the noninfectious inflammatory category, such as hidradenitis suppurativa, which could easily be misdiagnosed as an abscess.

Future Directions—Owing to limitations of a retrospective cohort study, we present several opportunities for further research on this vulnerable population. The severity of disease, especially infectious etiologies, should be graded to determine if NWH patients truly present later in the disease course. The duration and quality of housing for NWH patients could be categorized based on living conditions (eg, on the street vs in a shelter). Although the findings of our NWH cohort presenting to the ED at UMC provide helpful insight into dermatologic disease, these findings may be disparate from those conducted at other locations in the United States. University Medical Center provides care to mostly subsidized insurance plans in a racially diverse community. Improved outcomes for the NWH individuals living in New Orleans start with obtaining a greater understanding of their diseases and where disparities exist that can be bridged with better care.

Acknowledgment—The dataset generated during this study and used for analysis is not publicly available to protect public health information but is available from the corresponding author on reasonable request.

More than half a million individuals are without housing (NWH) on any given night in the United States, as estimated by the US Department of Housing and Urban Development. ¹ Lack of hygiene, increased risk of infection and infestation due to living conditions, and barriers to health care put these individuals at increased risk for disease. ² Skin disease, including fungal infection and acne, are within the top 10 most prevalent diseases worldwide and can cause major psychologic impairment, yet dermatologic concerns and clinical outcomes in NWH patients have not been well characterized. ^2-5 Further, because this vulnerable demographic tends to be underinsured, they frequently present to the emergency department (ED) for management of disease. ^1,6 Survey of common concerns in NWH patients is of utility to consulting dermatologists and nondermatologist providers in the ED, who can familiarize themselves with management of diseases they are more likely to encounter. Few studies examine dermatologic conditions in the ED, and a thorough literature review indicates none have included homelessness as a variable. ^6,7 Additionally, comparison with a matched control group of patients with housing (WH) is limited. ^5,8 We present one of the largest comparisons of cutaneous disease in NWH vs WH patients in a single hospital system to elucidate the types of cutaneous disease that motivate patients to seek care, the location of skin disease, and differences in clinical care.

Methods

A retrospective medical record review of patients seen for an inclusive list of dermatologic diagnoses in the ED or while admitted at University Medical Center New Orleans, Louisiana (UMC), between January 1, 2018, and April 21, 2020, was conducted. This study was qualified as exempt from the institutional review board by Louisiana State University because it proposed zero risk to the patients and remained completely anonymous. Eight hundred forty-two total medical records were reviewed (NWH, 421; WH, 421)(Table 1). Patients with housing were matched based on self-identified race and ethnicity, sex, and age. Disease categories were constructed based on fundamental pathophysiology adapted from Dermatology⁹: infectious, noninfectious inflammatory, neoplasm, trauma and wounds, drug-related eruptions, vascular, pruritic, pigmented, bullous, neuropsychiatric, and other. Other included unspecified eruptions as well as miscellaneous lesions such as calluses. The current chief concern, anatomic location, and configuration were recorded, as well as biopsied lesions and outpatient referrals or inpatient consultations to dermatology or other specialties, including wound care, infectious disease, podiatry, and surgery. χ² analysis was used to analyze significance of cutaneous categories, body location, and referrals. Groups smaller than 5 defaulted to the Fisher exact test.

Results

The total diagnoses (including both chief concerns and secondary diagnoses) are shown in Table 2. Chief concerns were more frequently cutaneous or dermatologic for WH (NWH, 209; WH, 307; P<.001). In both groups, cutaneous infectious etiologies were more likely to be a patient’s presenting chief concern (58% NWH, P=.002; 42% WH, P<.001). Noninfectious inflammatory etiologies and pigmented lesions were more likely to be secondary diagnoses with an unrelated noncutaneous concern; noninfectious inflammatory etiologies were only 16% of the total cutaneous chief concerns (11% NWH, P=.04; 20% WH, P=.03), and no pigmented lesions were chief concerns.

Infection was the most common chief concern, though NWH patients presented with significantly more infectious concerns (NWH, 212; WH, 150; P<.001), particularly infestations (NWH, 33; WH, 8; P<.001) and bacterial etiologies (NWH, 127; WH, 100; P=.04). The majority of bacterial etiologies were either an abscess or cellulitis (NWH, 106; WH, 83), though infected chronic wounds were categorized as bacterial infection when treated definitively as such (eg, in the case of sacral ulcers causing osteomyelitis)(NWH, 21; WH, 17). Of note, infectious etiology was associated with intravenous drug use (IVDU) in both NWH and WH patients. Of 184 NWH who reported IVDU, 127 had an infectious diagnosis (P<.001). Similarly, 43 of 56 total WH patients who reported IVDU had an infectious diagnosis (P<.001). Infestation (within the infectious category) included scabies (NWH, 20; WH, 3) and insect or arthropod bites (NWH, 12; WH, 5). Two NWH patients also presented with swelling of the lower extremities and were subsequently diagnosed with maggot infestations. Fungal and viral etiologies were not significantly increased in either group; however, NWH did have a higher incidence of tinea pedis (NWH, 14; WH, 4; P=.03).

More neoplasms (NWH, 6; WH, 16; P=.03), noninfectious inflammatory eruptions (NWH, 48; WH, 85; P<.001), and cutaneous drug eruptions (NWH, 5; WH, 27; P<.001) were reported in WH patients. There was no significant difference in benign vs malignant neoplastic processes between groups. More noninfectious inflammatory eruptions in WH were specifically driven by a markedly increased incidence of follicular (NWH, 9; WH, 29; P<.001) and urticarial/erythematous (NWH, 3; WH, 13; P=.02) lesions. Follicular etiologies included acne (NWH, 1; WH, 6; P=.12), folliculitis (NWH, 5; WH, 2; P=.45), hidradenitis suppurativa (NWH, 2; WH, 11; P=.02), and pilonidal and sebaceous cysts (NWH, 1; WH, 10; P=.01). Allergic urticaria dominated the urticarial/erythematous category (NWH, 3; WH, 11; P=.06), though there were 2 WH presentations of diffuse erythema and skin peeling.

Another substantial proportion of cutaneous etiologies were due to trauma or chronic wounds. Significantly more traumatic injuries presented in NWH patients vs WH patients (36 vs 31; P=.04). Trauma included human or dog bites (NWH, 5; WH, 4), sunburns (NWH, 3; WH, 0), other burns (NWH, 11; WH, 13), abrasions and lacerations (NWH, 16; WH, 3; P=.004), and foreign bodies (NWH, 1; WH, 1). Wounds consisted of chronic wounds such as those due to diabetes mellitus (foot ulcers) or immobility (sacral ulcers); numbers were similar between groups.

Looking at location, NWH patients had more pathology on the feet (NWH, 62; WH, 39; P=.02), whereas WH patients had more disseminated multiregional concerns (NWH, 55; WH, 75; P=.05). No one body location was notably more likely to warrant a chief concern.

For clinical outcomes, more WH patients received a consultation of any kind (NWH, 171; WH, 217; P<.001), consultation to dermatology (NWH, 49; WH, 87; P<.001), and consultation to surgery (NWH, 64; WH, 110; P<.001)(Table 3 and Figure). More outpatient referrals to dermatology were made for WH patients (NWH, 61; WH, 82; P=.05). Notably, NWH patients presented for 80% fewer hospital follow-up appointments (NWH, 11; WH, 55; P<.001). It is essential to note that these findings were not affected by self-reported race or ethnicity. Results remained significant when broken into cohorts consisting of patients with and without skin of color.

Comment

Cutaneous Concerns in NWH Patients—Although cutaneous disease has been reported to disproportionately affect NWH patients,¹⁰ in our cohort, NWH patients had fewer cutaneous chief concerns than WH patients. However, without comparing with all patients entering the ED at UMC, we cannot make a statement on this claim. We do present a few reasons why NWH patients do not have more cutaneous concerns. First, they may wait to present with cutaneous disease until it becomes more severe (eg, until chronic wounds have progressed to infections). Second, as discussed in depth by Hollestein and Nijsten,³ dermatologic disease may be a major contributor to the overall count of disability-adjusted life years but may play a minor role in individual disability. Therefore, skin disease often is considered less important on an individual basis, despite substantial psychosocial burden, leading to further stigmatization of this vulnerable population and discouraged care-seeking behavior, particularly for noninfectious inflammatory eruptions, which were notably more present in WH individuals. Third, fewer dermatologic lesions were reported on NWH patients, which may explain why all 3 WH pigmented lesions were diagnosed after presentation with a noncutaneous concern (eg, headache, anemia, nausea).

Infectious Cutaneous Diagnoses—The increased presentation of infectious etiologies, especially bacterial, is linked to the increased numbers of IVDUs reported in NWH individuals as well as increased exposure and decreased access to basic hygienic supplies. Intravenous drug use acted as an effect modifier of infectious etiology diagnoses, playing a major role in both NWH and WH cohorts. Although Black and Hispanic individuals as well as individuals with low socioeconomic status have increased proportions of skin cancer, there are inadequate data on the prevalence in NWH individuals.⁴ We found no increase in malignant dermatologic processes in NWH individuals; however, this may be secondary to inadequate screening with a total body skin examination.

Clinical Workup of NWH Patients—Because most NWH individuals present to the ED to receive care, their care compared with WH patients should be considered. In this cohort, WH patients received a less extensive clinical workup. They received almost half as many dermatologic consultations and fewer outpatient referrals to dermatology. Major communication barriers may affect NWH presentation to follow-up, which was drastically lower than WH individuals, as scheduling typically occurs well after discharge from the ED or inpatient unit. We suggest a few alterations to improve dermatologic care for NWH individuals:

• Consider inpatient consultation for serious dermatologic conditions—even if chronic—to improve disease control, considering that many barriers inhibit follow-up in clinic.

• Involve outreach teams, such as the Assertive Community Treatment teams, that assist individuals by delivering medicine for psychiatric disorders, conducting total-body skin examinations, assisting with wound care, providing basic skin barrier creams or medicaments, and carrying information regarding outpatient follow-up.

• Educate ED providers on the most common skin concerns, especially those that fall within the noninfectious inflammatory category, such as hidradenitis suppurativa, which could easily be misdiagnosed as an abscess.

Future Directions—Owing to limitations of a retrospective cohort study, we present several opportunities for further research on this vulnerable population. The severity of disease, especially infectious etiologies, should be graded to determine if NWH patients truly present later in the disease course. The duration and quality of housing for NWH patients could be categorized based on living conditions (eg, on the street vs in a shelter). Although the findings of our NWH cohort presenting to the ED at UMC provide helpful insight into dermatologic disease, these findings may be disparate from those conducted at other locations in the United States. University Medical Center provides care to mostly subsidized insurance plans in a racially diverse community. Improved outcomes for the NWH individuals living in New Orleans start with obtaining a greater understanding of their diseases and where disparities exist that can be bridged with better care.

Acknowledgment—The dataset generated during this study and used for analysis is not publicly available to protect public health information but is available from the corresponding author on reasonable request.

Dedicator of cytokinesis 8 (DOCK8 ) deficiency is the major cause of autosomal-recessive hyper-IgEsyndrome. ¹ Characteristic clinical features including eosinophilia, eczema, and recurrent Staphylococcus aureus cutaneous and respiratory tract infections are common in DOCK8 deficiency, similar to the autosomal-dominant form of hyper-IgE syndrome that is due to defi c iency of signal transducer and activation of transcription 3 (STAT-3 ). ¹ In addition, patients with DOCK8 deficiency are particularly susceptible to asthma; food allergies; lymphomas; and severe cutaneous viral infections, including herpes simplex virus (HSV), molluscum contagiosum, varicella-zoster virus, and human papillomavirus. Since the discovery of the DOCK8 gene in 2009, various studies have sought to elucidate the mechanistic contribution of DOCK8 to the dermatologic immune environment. ² Although cutaneous viral infections such as those caused by HSV typically are short lived and self-limiting in immunocompetent hosts, they have proven to be severe and recalcitrant in the setting of DOCK8 deficiency. ¹ Herein, we report the case of a 32-month-old girl with homozygous DOCK8 deficiency who developed acyclovir-resistant cutaneous HSV. 

Case Report

A 32-month-old girl presented with an approximately 2-cm linear erosion along the left posterior auricular sulcus at month 9 of a hospital stay for recurrent infections. Her medical history was notable for multiple upper respiratory tract infections, diffuse eczema, and food allergies. She had presented to an outside hospital at 14 months of age with herpetic gingivostomatitis and eczema herpeticum that was successfully treated with acyclovir. She was readmitted at 20 months of age due to Pneumocystis jiroveci pneumonia, pancytopenia, and disseminated histoplasmosis. Prophylactic oral acyclovir (20 mg/kg twice daily) was started, given her history of HSV infection. Because of recurrent infections, she underwent an immunodeficiency workup. Whole exome sequencing analysis revealed a homozygous deletion c.(528+1_529−1)_(1516+1_1517−1)del in DOCK8 gene–affecting exons 5 to 13. The patient was transferred to our hospital for continued care and as a potential candidate for bone marrow transplant following resolution of the disseminated histoplasmosis infection.

During her hospitalization at the current presentation, she was noted to have a 2-cm linear erosion along the left posterior auricular sulcus. Initial wound care with bacitracin ointment was applied to the area while specimens were obtained and empiric oral acyclovir therapy was initiated (20 mg/kg 4 times daily [QID]), given a clinical impression consistent with cutaneous HSV infection despite acyclovir prophylaxis. Direct immunofluorescence and viral cultures were positive for HSV-1, while bacterial cultures grew methicillin-susceptible S aureus. Cephalexin and mupirocin ointment were started, and acyclovir was continued. After 2 weeks of therapy, there was no visible change in the wound; cultures were repeated, again showing the wound contained HSV. Bacterial cultures this time grew Pseudomonas putida, and the antibiotic regimen was transitioned to cefepime.

After no response to the continued course of therapeutic acyclovir, HSV cultures were sent to the Centers for Disease Control and Prevention for resistance testing, and biopsy of the lesion was performed by the otolaryngology service to rule out malignancy and potential alternative diagnoses. Histopathology showed only reactive inflammation without visible microorganisms on tissue HSV-1/HSV-2 immunostain; however, tissue viral culture was positive for HSV-1. The patient was transitioned back to acyclovir (intravenous [IV] 20 mg/kg QID) with the addition of empiric foscarnet (IV 40 mg/kg 3 times daily) given the worsening appearance of the lesion.  The HSV acyclovir resistance test results from the Centers for Disease Control and Prevention returned soon after and were positive for resistance (median infectious dose, 3.29 µg/L [reference interval, sensitive <2.00 µg/L; resistant >1.90 µg/L]). The patient completed a 21-day course of combination foscarnet and acyclovir therapy, during which time the lesion showed notable improvement and healing. The patient was continued on prophylactic acyclovir (IV 20 mg/kg QID). Unfortunately, the patient eventually died due to complications related to pneumonia.

Comment

Infection in Patients With DOCK8 Deficiency—The gene DOCK8 has emerged as playing a central role in both innate and adaptive immunity, as it is expressed primarily in immune cells and serves as a mediator of numerous processes, including immune synapse formation, cell signaling and trafficking, antibody and cytokine production, and lymphocyte memory.³ Cells that are critical for combating cutaneous viral infections, including skin-resident memory T cells and natural killer cells, are defective, which leads to a severely immunocompromised state in DOCK8-deficient patients with a particular susceptibility to infectious and inflammatory dermatologic disease.⁴ 

Herpes simplex virus infection commonly is seen in DOCK8 deficiency, with retrospective analysis of a DOCK8-deficient cohort revealing HSV infection in approximately 38% of patients.⁵ Prophylactic acyclovir is essential for DOCK8-deficient individuals with a history of HSV infection given the tendency of the virus to reactivate.⁶ However, despite prophylaxis, our patient developed an HSV-positive posterior auricular erosion that continued to progress even after increase of the acyclovir dose. Acyclovir resistance testing of the HSV isolated from the wound was positive, confirming the clinical suspicion of the presence of acyclovir-resistant HSV infection.

Acyclovir-Resistant HSV—Acyclovir-resistant HSV in immunosuppressed individuals was first noted in 1982, and most cases since then have occurred in the setting of AIDS and in organ transplant recipients.⁶ Few reports of acyclovir-resistant HSV in DOCK8 deficiency exist, and to our knowledge, our patient is the youngest DOCK8-deficient individual to be documented with acyclovir-resistant HSV infection.^1,7-15 We identified relevant cases from the PubMed and EMBASE databases using the search terms DOCK8 deficiency and acyclovir and DOCK8 deficiency and herpes. The eTable lists other reported cases of acyclovir-resistant HSV in DOCK8-deficient patients. The majority of cases involved school-aged females. Lesion types varied and included herpes labialis, eczema herpeticum, and blepharoconjunctivitis. Escalation of therapy and resolution of the lesion was seen in some cases with administration of subcutaneous pegylated interferon alfa-2b.

Treatment Alternatives—Acyclovir competitively inhibits viral DNA polymerase by incorporating into elongating viral DNA strands and halting chain synthesis. Acyclovir requires triphosphorylation for activation, and viral thymidine kinase is responsible for the first phosphorylation event. Ninety-five percent of cases of acyclovir resistance are secondary to mutations in viral thymidine kinase. Foscarnet also inhibits viral DNA polymerase but does so directly without the need to be phosphorylated first.⁶ For this reason, foscarnet often is the drug of choice in the treatment of acyclovir-resistant HSV, as evidenced in our patient. However, foscarnet-resistant HSV strains may develop from mutations in the DNA polymerase gene.

Cidofovir is a nucleotide analogue that requires phosphorylation by host, as opposed to viral, kinases for antiviral activity. Intravenous and topical formulations of cidofovir have proven effective in the treatment of acyclovir- and foscarnet-resistant HSV lesions.⁶ Cidofovir also can be applied intralesionally, a method that provides targeted therapy and minimizes cidofovir-associated nephrotoxicity.¹² Reports of systemic interferon alfa therapy for acyclovir-resistant HSV also exist. A study found IFN-⍺ production by peripheral blood mononuclear cells in DOCK8-deficient individuals to be significantly reduced relative to controls (P<.05).⁷ There has been complete resolution of acyclovir-resistant HSV lesions with subcutaneous pegylated interferon alfa-2b injections in several DOCK8-deficient patients.^7-9

The need for escalating therapy in DOCK8-deficient individuals with acyclovir-resistant HSV infection underscores the essential role of DOCK8 in dermatologic immunity. Our case demonstrates that a high degree of suspicion for cutaneous HSV infection should be adopted in DOCK8-deficient patients of any age, regardless of acyclovir prophylaxis. Viral culture in addition to bacterial cultures should be performed early in patients with cutaneous erosions, and the threshold for HSV resistance testing should be low to minimize morbidity associated with these infections. Early resistance testing in our case could have prevented prolongation of infection and likely eliminated the need for a biopsy.

Conclusion

DOCK8 deficiency presents a unique challenge to dermatologists and other health care providers given the susceptibility of affected individuals to developing a reservoir of severe and potentially resistant viral cutaneous infections. Prophylactic acyclovir may not be sufficient for HSV suppression, even in the youngest of patients, and suspicion for resistance should be high to avoid delays in adequate treatment.

Dedicator of cytokinesis 8 (DOCK8 ) deficiency is the major cause of autosomal-recessive hyper-IgEsyndrome. ¹ Characteristic clinical features including eosinophilia, eczema, and recurrent Staphylococcus aureus cutaneous and respiratory tract infections are common in DOCK8 deficiency, similar to the autosomal-dominant form of hyper-IgE syndrome that is due to defi c iency of signal transducer and activation of transcription 3 (STAT-3 ). ¹ In addition, patients with DOCK8 deficiency are particularly susceptible to asthma; food allergies; lymphomas; and severe cutaneous viral infections, including herpes simplex virus (HSV), molluscum contagiosum, varicella-zoster virus, and human papillomavirus. Since the discovery of the DOCK8 gene in 2009, various studies have sought to elucidate the mechanistic contribution of DOCK8 to the dermatologic immune environment. ² Although cutaneous viral infections such as those caused by HSV typically are short lived and self-limiting in immunocompetent hosts, they have proven to be severe and recalcitrant in the setting of DOCK8 deficiency. ¹ Herein, we report the case of a 32-month-old girl with homozygous DOCK8 deficiency who developed acyclovir-resistant cutaneous HSV. 

Case Report

A 32-month-old girl presented with an approximately 2-cm linear erosion along the left posterior auricular sulcus at month 9 of a hospital stay for recurrent infections. Her medical history was notable for multiple upper respiratory tract infections, diffuse eczema, and food allergies. She had presented to an outside hospital at 14 months of age with herpetic gingivostomatitis and eczema herpeticum that was successfully treated with acyclovir. She was readmitted at 20 months of age due to Pneumocystis jiroveci pneumonia, pancytopenia, and disseminated histoplasmosis. Prophylactic oral acyclovir (20 mg/kg twice daily) was started, given her history of HSV infection. Because of recurrent infections, she underwent an immunodeficiency workup. Whole exome sequencing analysis revealed a homozygous deletion c.(528+1_529−1)_(1516+1_1517−1)del in DOCK8 gene–affecting exons 5 to 13. The patient was transferred to our hospital for continued care and as a potential candidate for bone marrow transplant following resolution of the disseminated histoplasmosis infection.

During her hospitalization at the current presentation, she was noted to have a 2-cm linear erosion along the left posterior auricular sulcus. Initial wound care with bacitracin ointment was applied to the area while specimens were obtained and empiric oral acyclovir therapy was initiated (20 mg/kg 4 times daily [QID]), given a clinical impression consistent with cutaneous HSV infection despite acyclovir prophylaxis. Direct immunofluorescence and viral cultures were positive for HSV-1, while bacterial cultures grew methicillin-susceptible S aureus. Cephalexin and mupirocin ointment were started, and acyclovir was continued. After 2 weeks of therapy, there was no visible change in the wound; cultures were repeated, again showing the wound contained HSV. Bacterial cultures this time grew Pseudomonas putida, and the antibiotic regimen was transitioned to cefepime.

After no response to the continued course of therapeutic acyclovir, HSV cultures were sent to the Centers for Disease Control and Prevention for resistance testing, and biopsy of the lesion was performed by the otolaryngology service to rule out malignancy and potential alternative diagnoses. Histopathology showed only reactive inflammation without visible microorganisms on tissue HSV-1/HSV-2 immunostain; however, tissue viral culture was positive for HSV-1. The patient was transitioned back to acyclovir (intravenous [IV] 20 mg/kg QID) with the addition of empiric foscarnet (IV 40 mg/kg 3 times daily) given the worsening appearance of the lesion.  The HSV acyclovir resistance test results from the Centers for Disease Control and Prevention returned soon after and were positive for resistance (median infectious dose, 3.29 µg/L [reference interval, sensitive <2.00 µg/L; resistant >1.90 µg/L]). The patient completed a 21-day course of combination foscarnet and acyclovir therapy, during which time the lesion showed notable improvement and healing. The patient was continued on prophylactic acyclovir (IV 20 mg/kg QID). Unfortunately, the patient eventually died due to complications related to pneumonia.

Comment

Infection in Patients With DOCK8 Deficiency—The gene DOCK8 has emerged as playing a central role in both innate and adaptive immunity, as it is expressed primarily in immune cells and serves as a mediator of numerous processes, including immune synapse formation, cell signaling and trafficking, antibody and cytokine production, and lymphocyte memory.³ Cells that are critical for combating cutaneous viral infections, including skin-resident memory T cells and natural killer cells, are defective, which leads to a severely immunocompromised state in DOCK8-deficient patients with a particular susceptibility to infectious and inflammatory dermatologic disease.⁴ 

Herpes simplex virus infection commonly is seen in DOCK8 deficiency, with retrospective analysis of a DOCK8-deficient cohort revealing HSV infection in approximately 38% of patients.⁵ Prophylactic acyclovir is essential for DOCK8-deficient individuals with a history of HSV infection given the tendency of the virus to reactivate.⁶ However, despite prophylaxis, our patient developed an HSV-positive posterior auricular erosion that continued to progress even after increase of the acyclovir dose. Acyclovir resistance testing of the HSV isolated from the wound was positive, confirming the clinical suspicion of the presence of acyclovir-resistant HSV infection.

Acyclovir-Resistant HSV—Acyclovir-resistant HSV in immunosuppressed individuals was first noted in 1982, and most cases since then have occurred in the setting of AIDS and in organ transplant recipients.⁶ Few reports of acyclovir-resistant HSV in DOCK8 deficiency exist, and to our knowledge, our patient is the youngest DOCK8-deficient individual to be documented with acyclovir-resistant HSV infection.^1,7-15 We identified relevant cases from the PubMed and EMBASE databases using the search terms DOCK8 deficiency and acyclovir and DOCK8 deficiency and herpes. The eTable lists other reported cases of acyclovir-resistant HSV in DOCK8-deficient patients. The majority of cases involved school-aged females. Lesion types varied and included herpes labialis, eczema herpeticum, and blepharoconjunctivitis. Escalation of therapy and resolution of the lesion was seen in some cases with administration of subcutaneous pegylated interferon alfa-2b.

Treatment Alternatives—Acyclovir competitively inhibits viral DNA polymerase by incorporating into elongating viral DNA strands and halting chain synthesis. Acyclovir requires triphosphorylation for activation, and viral thymidine kinase is responsible for the first phosphorylation event. Ninety-five percent of cases of acyclovir resistance are secondary to mutations in viral thymidine kinase. Foscarnet also inhibits viral DNA polymerase but does so directly without the need to be phosphorylated first.⁶ For this reason, foscarnet often is the drug of choice in the treatment of acyclovir-resistant HSV, as evidenced in our patient. However, foscarnet-resistant HSV strains may develop from mutations in the DNA polymerase gene.

Cidofovir is a nucleotide analogue that requires phosphorylation by host, as opposed to viral, kinases for antiviral activity. Intravenous and topical formulations of cidofovir have proven effective in the treatment of acyclovir- and foscarnet-resistant HSV lesions.⁶ Cidofovir also can be applied intralesionally, a method that provides targeted therapy and minimizes cidofovir-associated nephrotoxicity.¹² Reports of systemic interferon alfa therapy for acyclovir-resistant HSV also exist. A study found IFN-⍺ production by peripheral blood mononuclear cells in DOCK8-deficient individuals to be significantly reduced relative to controls (P<.05).⁷ There has been complete resolution of acyclovir-resistant HSV lesions with subcutaneous pegylated interferon alfa-2b injections in several DOCK8-deficient patients.^7-9

The need for escalating therapy in DOCK8-deficient individuals with acyclovir-resistant HSV infection underscores the essential role of DOCK8 in dermatologic immunity. Our case demonstrates that a high degree of suspicion for cutaneous HSV infection should be adopted in DOCK8-deficient patients of any age, regardless of acyclovir prophylaxis. Viral culture in addition to bacterial cultures should be performed early in patients with cutaneous erosions, and the threshold for HSV resistance testing should be low to minimize morbidity associated with these infections. Early resistance testing in our case could have prevented prolongation of infection and likely eliminated the need for a biopsy.

Conclusion

DOCK8 deficiency presents a unique challenge to dermatologists and other health care providers given the susceptibility of affected individuals to developing a reservoir of severe and potentially resistant viral cutaneous infections. Prophylactic acyclovir may not be sufficient for HSV suppression, even in the youngest of patients, and suspicion for resistance should be high to avoid delays in adequate treatment.

Dedicator of cytokinesis 8 (DOCK8 ) deficiency is the major cause of autosomal-recessive hyper-IgEsyndrome. ¹ Characteristic clinical features including eosinophilia, eczema, and recurrent Staphylococcus aureus cutaneous and respiratory tract infections are common in DOCK8 deficiency, similar to the autosomal-dominant form of hyper-IgE syndrome that is due to defi c iency of signal transducer and activation of transcription 3 (STAT-3 ). ¹ In addition, patients with DOCK8 deficiency are particularly susceptible to asthma; food allergies; lymphomas; and severe cutaneous viral infections, including herpes simplex virus (HSV), molluscum contagiosum, varicella-zoster virus, and human papillomavirus. Since the discovery of the DOCK8 gene in 2009, various studies have sought to elucidate the mechanistic contribution of DOCK8 to the dermatologic immune environment. ² Although cutaneous viral infections such as those caused by HSV typically are short lived and self-limiting in immunocompetent hosts, they have proven to be severe and recalcitrant in the setting of DOCK8 deficiency. ¹ Herein, we report the case of a 32-month-old girl with homozygous DOCK8 deficiency who developed acyclovir-resistant cutaneous HSV. 

Case Report

A 32-month-old girl presented with an approximately 2-cm linear erosion along the left posterior auricular sulcus at month 9 of a hospital stay for recurrent infections. Her medical history was notable for multiple upper respiratory tract infections, diffuse eczema, and food allergies. She had presented to an outside hospital at 14 months of age with herpetic gingivostomatitis and eczema herpeticum that was successfully treated with acyclovir. She was readmitted at 20 months of age due to Pneumocystis jiroveci pneumonia, pancytopenia, and disseminated histoplasmosis. Prophylactic oral acyclovir (20 mg/kg twice daily) was started, given her history of HSV infection. Because of recurrent infections, she underwent an immunodeficiency workup. Whole exome sequencing analysis revealed a homozygous deletion c.(528+1_529−1)_(1516+1_1517−1)del in DOCK8 gene–affecting exons 5 to 13. The patient was transferred to our hospital for continued care and as a potential candidate for bone marrow transplant following resolution of the disseminated histoplasmosis infection.

During her hospitalization at the current presentation, she was noted to have a 2-cm linear erosion along the left posterior auricular sulcus. Initial wound care with bacitracin ointment was applied to the area while specimens were obtained and empiric oral acyclovir therapy was initiated (20 mg/kg 4 times daily [QID]), given a clinical impression consistent with cutaneous HSV infection despite acyclovir prophylaxis. Direct immunofluorescence and viral cultures were positive for HSV-1, while bacterial cultures grew methicillin-susceptible S aureus. Cephalexin and mupirocin ointment were started, and acyclovir was continued. After 2 weeks of therapy, there was no visible change in the wound; cultures were repeated, again showing the wound contained HSV. Bacterial cultures this time grew Pseudomonas putida, and the antibiotic regimen was transitioned to cefepime.

After no response to the continued course of therapeutic acyclovir, HSV cultures were sent to the Centers for Disease Control and Prevention for resistance testing, and biopsy of the lesion was performed by the otolaryngology service to rule out malignancy and potential alternative diagnoses. Histopathology showed only reactive inflammation without visible microorganisms on tissue HSV-1/HSV-2 immunostain; however, tissue viral culture was positive for HSV-1. The patient was transitioned back to acyclovir (intravenous [IV] 20 mg/kg QID) with the addition of empiric foscarnet (IV 40 mg/kg 3 times daily) given the worsening appearance of the lesion.  The HSV acyclovir resistance test results from the Centers for Disease Control and Prevention returned soon after and were positive for resistance (median infectious dose, 3.29 µg/L [reference interval, sensitive <2.00 µg/L; resistant >1.90 µg/L]). The patient completed a 21-day course of combination foscarnet and acyclovir therapy, during which time the lesion showed notable improvement and healing. The patient was continued on prophylactic acyclovir (IV 20 mg/kg QID). Unfortunately, the patient eventually died due to complications related to pneumonia.

Comment

Infection in Patients With DOCK8 Deficiency—The gene DOCK8 has emerged as playing a central role in both innate and adaptive immunity, as it is expressed primarily in immune cells and serves as a mediator of numerous processes, including immune synapse formation, cell signaling and trafficking, antibody and cytokine production, and lymphocyte memory.³ Cells that are critical for combating cutaneous viral infections, including skin-resident memory T cells and natural killer cells, are defective, which leads to a severely immunocompromised state in DOCK8-deficient patients with a particular susceptibility to infectious and inflammatory dermatologic disease.⁴ 

Herpes simplex virus infection commonly is seen in DOCK8 deficiency, with retrospective analysis of a DOCK8-deficient cohort revealing HSV infection in approximately 38% of patients.⁵ Prophylactic acyclovir is essential for DOCK8-deficient individuals with a history of HSV infection given the tendency of the virus to reactivate.⁶ However, despite prophylaxis, our patient developed an HSV-positive posterior auricular erosion that continued to progress even after increase of the acyclovir dose. Acyclovir resistance testing of the HSV isolated from the wound was positive, confirming the clinical suspicion of the presence of acyclovir-resistant HSV infection.

Acyclovir-Resistant HSV—Acyclovir-resistant HSV in immunosuppressed individuals was first noted in 1982, and most cases since then have occurred in the setting of AIDS and in organ transplant recipients.⁶ Few reports of acyclovir-resistant HSV in DOCK8 deficiency exist, and to our knowledge, our patient is the youngest DOCK8-deficient individual to be documented with acyclovir-resistant HSV infection.^1,7-15 We identified relevant cases from the PubMed and EMBASE databases using the search terms DOCK8 deficiency and acyclovir and DOCK8 deficiency and herpes. The eTable lists other reported cases of acyclovir-resistant HSV in DOCK8-deficient patients. The majority of cases involved school-aged females. Lesion types varied and included herpes labialis, eczema herpeticum, and blepharoconjunctivitis. Escalation of therapy and resolution of the lesion was seen in some cases with administration of subcutaneous pegylated interferon alfa-2b.

Treatment Alternatives—Acyclovir competitively inhibits viral DNA polymerase by incorporating into elongating viral DNA strands and halting chain synthesis. Acyclovir requires triphosphorylation for activation, and viral thymidine kinase is responsible for the first phosphorylation event. Ninety-five percent of cases of acyclovir resistance are secondary to mutations in viral thymidine kinase. Foscarnet also inhibits viral DNA polymerase but does so directly without the need to be phosphorylated first.⁶ For this reason, foscarnet often is the drug of choice in the treatment of acyclovir-resistant HSV, as evidenced in our patient. However, foscarnet-resistant HSV strains may develop from mutations in the DNA polymerase gene.

Cidofovir is a nucleotide analogue that requires phosphorylation by host, as opposed to viral, kinases for antiviral activity. Intravenous and topical formulations of cidofovir have proven effective in the treatment of acyclovir- and foscarnet-resistant HSV lesions.⁶ Cidofovir also can be applied intralesionally, a method that provides targeted therapy and minimizes cidofovir-associated nephrotoxicity.¹² Reports of systemic interferon alfa therapy for acyclovir-resistant HSV also exist. A study found IFN-⍺ production by peripheral blood mononuclear cells in DOCK8-deficient individuals to be significantly reduced relative to controls (P<.05).⁷ There has been complete resolution of acyclovir-resistant HSV lesions with subcutaneous pegylated interferon alfa-2b injections in several DOCK8-deficient patients.^7-9

The need for escalating therapy in DOCK8-deficient individuals with acyclovir-resistant HSV infection underscores the essential role of DOCK8 in dermatologic immunity. Our case demonstrates that a high degree of suspicion for cutaneous HSV infection should be adopted in DOCK8-deficient patients of any age, regardless of acyclovir prophylaxis. Viral culture in addition to bacterial cultures should be performed early in patients with cutaneous erosions, and the threshold for HSV resistance testing should be low to minimize morbidity associated with these infections. Early resistance testing in our case could have prevented prolongation of infection and likely eliminated the need for a biopsy.

Conclusion

DOCK8 deficiency presents a unique challenge to dermatologists and other health care providers given the susceptibility of affected individuals to developing a reservoir of severe and potentially resistant viral cutaneous infections. Prophylactic acyclovir may not be sufficient for HSV suppression, even in the youngest of patients, and suspicion for resistance should be high to avoid delays in adequate treatment.

Fear of antibiotic overuse and frustration with physicians who prescribe them too freely are key sentiments expressed by women with recurrent urinary tract infections (rUTIs), according to findings from a study involving six focus groups.

“Here in our female pelvic medicine reconstructive urology clinic at Cedars-Sinai and at UCLA, we see many women who are referred for evaluation of rUTIs who are very frustrated with their care,” Victoria Scott, MD, Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“So with these focus groups, we saw an opportunity to explore why women are so frustrated and to try and improve the care delivered,” she added.

Findings from the study were published online Sept. 1 in The Journal of Urology.

“There is a need for physicians to modify management strategies ... and to devote more research efforts to improving nonantibiotic options for the prevention and treatment of recurrent urinary tract infections, as well as management strategies that better empower patients,” the authors wrote.
 

Six focus groups

Four or five participants were included in each of the six focus groups – a total of 29 women. All participants reported a history of symptomatic, culture-proven UTI episodes. They had experienced two or more infections in 6 months or three or more infections within 1 year. Women were predominantly White. Most were employed part- or full-time and held a college degree.

From a qualitative analysis of all focus group transcripts, two main themes emerged:

• The negative impact of taking antibiotics for the prevention and treatment of rUTIs.
• Resentment of the medical profession for the way it managed rUTIs.

The researchers found that participants had a good understanding of the deleterious effects from inappropriate antibiotic use, largely gleaned from media sources and the Internet. “Numerous women stated that they had reached such a level of concern about antibiotics that they would resist taking them for prevention or treatment of infections,” Dr. Scott and colleagues pointed out.

These concerns centered around the risk of developing resistance to antibiotics and the ill effects that antibiotics can have on the gastrointestinal and genitourinary microbiomes. Several women reported that they had developed Clostridium difficile infections after taking antibiotics; one of the patients required hospitalization for the infection.

Women also reported concerns that they had been given an antibiotic needlessly for symptoms that might have been caused by a genitourinary condition other than a UTI. They also reported feeling resentful toward practitioners, particularly if they felt the practitioner was overprescribing antibiotics. Some had resorted to consultations with alternative practitioners, such as herbalists. “A second concern discussed by participants was the feeling of being ignored by physicians,” the authors observed.

In this regard, the women felt that their physicians underestimated the burden that rUTIs had on their lives and the detrimental effect that repeated infections had on their relationships, work, and overall quality of life. “These perceptions led to a prevalent mistrust of physicians,” the investigators wrote. This prompted many women to insist that the medical community devote more effort to the development of nonantibiotic options for the prevention and treatment of UTIs.
 

Improved management strategies

Asked how physicians might improve their management of rUTIs, Dr. Scott shared a number of suggestions. Cardinal rule No. 1: Have the patient undergo a urinalysis to make sure she does have a UTI. “There is a subset of patients among women with rUTIs who come in with a diagnosis of an rUTI but who really have not had documentation of more than one positive urine culture,” Dr. Scott noted. Such a history suggests that they do not have an rUTI.

It’s imperative that physicians rule out commonly misdiagnosed disorders, such as overactive bladder, as a cause of the patient’s symptoms. Symptoms of overactive bladder and rUTIs often overlap. While waiting for results from the urinalysis to confirm or rule out a UTI, young and healthy women may be prescribed a nonsteroidal anti-inflammatory drug (NSAID), such as naproxen, which can help ameliorate symptoms.

Because UTIs are frequently self-limiting, Dr. Scott and others have found that for young, otherwise healthy women, NSAIDs alone can often resolve symptoms of the UTI without use of an antibiotic. For relatively severe symptoms, a urinary analgesic, such as phenazopyridine (Pyridium), may soothe the lining of the urinary tract and relieve pain. Cystex is an over-the-counter urinary analgesic that women can procure themselves, Dr. Scott added.

If an antibiotic is indicated, those most commonly prescribed for a single episode of acute cystitis are nitrofurantoin and sulfamethoxazole plus trimethoprim (Bactrim). For recurrent UTIs, “patients are a bit more complicated,” Dr. Scott admitted. “I think the best practice is to look back at a woman’s prior urine culture and select an antibiotic that showed good sensitivity in the last positive urine test,” she said.

Prevention starts with behavioral strategies, such as voiding after sexual intercourse and wiping from front to back following urination to avoid introducing fecal bacteria into the urethra. Evidence suggests that premenopausal women who drink at least 1.5 L of water a day have significantly fewer UTI episodes, Dr. Scott noted. There is also “pretty good” evidence that cranberry supplements (not juice) can prevent rUTIs. Use of cranberry supplements is supported by the American Urological Association (conditional recommendation; evidence level of grade C).

For peri- and postmenopausal women, vaginal estrogen may be effective. It’s use for UTI prevention is well supported by the literature. Although not as well supported by evidence, some women find that a supplement such as D-mannose may prevent or treat UTIs by causing bacteria to bind to it rather than to the bladder wall. Probiotics are another possibility, she noted. Empathy can’t hurt, she added.

“A common theme among satisfied women was the sentiment that their physicians understood their problems and had a system in place to allow rapid diagnosis and treatment for UTI episodes,” the authors emphasized.

“[Such attitudes] highlight the need to investigate each patient’s experience and perceptions to allow for shared decision making regarding the management of rUTIs,” they wrote.
 

Further commentary

Asked to comment on the findings, editorialist Michelle Van Kuiken, MD, assistant professor of urology, University of California, San Francisco, acknowledged that there is not a lot of good evidence to support many of the strategies recommended by the American Urological Association to prevent and treat rUTIs, but she often follows these recommendations anyway. “The one statement in the guidelines that is the most supported by evidence is the use of cranberry supplements, and I do routinely recommended daily use of some form of concentrated cranberry supplements for all of my patients with rUTIs,” she said in an interview.

Dr. Van Kuiken said that vaginal estrogen is a very good option for all postmenopausal women who suffer from rUTIs and that there is growing acceptance of its use for this and other indications. There is some evidence to support D-mannose as well, although it’s not that robust, she acknowledged.

She said the evidence supporting the use of probiotics for this indication is very thin. She does not routinely recommend them for rUTIs, although they are not inherently harmful. “I think for a lot of women who have rUTIs, it can be pretty debilitating and upsetting for them – it can impact travel plans, work, and social events,” Dr. Van Kuiken said.

“Until we develop better diagnostic and therapeutic strategies, validating women’s experiences and concerns with rUTI while limiting unnecessary antibiotics remains our best option,” she wrote.

Dr. Scott and Dr. Van Kuiken have disclosed no relevant financial relationships.

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

Fear of antibiotic overuse and frustration with physicians who prescribe them too freely are key sentiments expressed by women with recurrent urinary tract infections (rUTIs), according to findings from a study involving six focus groups.

“Here in our female pelvic medicine reconstructive urology clinic at Cedars-Sinai and at UCLA, we see many women who are referred for evaluation of rUTIs who are very frustrated with their care,” Victoria Scott, MD, Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“So with these focus groups, we saw an opportunity to explore why women are so frustrated and to try and improve the care delivered,” she added.

Findings from the study were published online Sept. 1 in The Journal of Urology.

“There is a need for physicians to modify management strategies ... and to devote more research efforts to improving nonantibiotic options for the prevention and treatment of recurrent urinary tract infections, as well as management strategies that better empower patients,” the authors wrote.
 

Six focus groups

Four or five participants were included in each of the six focus groups – a total of 29 women. All participants reported a history of symptomatic, culture-proven UTI episodes. They had experienced two or more infections in 6 months or three or more infections within 1 year. Women were predominantly White. Most were employed part- or full-time and held a college degree.

From a qualitative analysis of all focus group transcripts, two main themes emerged:

• The negative impact of taking antibiotics for the prevention and treatment of rUTIs.
• Resentment of the medical profession for the way it managed rUTIs.

The researchers found that participants had a good understanding of the deleterious effects from inappropriate antibiotic use, largely gleaned from media sources and the Internet. “Numerous women stated that they had reached such a level of concern about antibiotics that they would resist taking them for prevention or treatment of infections,” Dr. Scott and colleagues pointed out.

These concerns centered around the risk of developing resistance to antibiotics and the ill effects that antibiotics can have on the gastrointestinal and genitourinary microbiomes. Several women reported that they had developed Clostridium difficile infections after taking antibiotics; one of the patients required hospitalization for the infection.

Women also reported concerns that they had been given an antibiotic needlessly for symptoms that might have been caused by a genitourinary condition other than a UTI. They also reported feeling resentful toward practitioners, particularly if they felt the practitioner was overprescribing antibiotics. Some had resorted to consultations with alternative practitioners, such as herbalists. “A second concern discussed by participants was the feeling of being ignored by physicians,” the authors observed.

In this regard, the women felt that their physicians underestimated the burden that rUTIs had on their lives and the detrimental effect that repeated infections had on their relationships, work, and overall quality of life. “These perceptions led to a prevalent mistrust of physicians,” the investigators wrote. This prompted many women to insist that the medical community devote more effort to the development of nonantibiotic options for the prevention and treatment of UTIs.
 

Improved management strategies

Asked how physicians might improve their management of rUTIs, Dr. Scott shared a number of suggestions. Cardinal rule No. 1: Have the patient undergo a urinalysis to make sure she does have a UTI. “There is a subset of patients among women with rUTIs who come in with a diagnosis of an rUTI but who really have not had documentation of more than one positive urine culture,” Dr. Scott noted. Such a history suggests that they do not have an rUTI.

It’s imperative that physicians rule out commonly misdiagnosed disorders, such as overactive bladder, as a cause of the patient’s symptoms. Symptoms of overactive bladder and rUTIs often overlap. While waiting for results from the urinalysis to confirm or rule out a UTI, young and healthy women may be prescribed a nonsteroidal anti-inflammatory drug (NSAID), such as naproxen, which can help ameliorate symptoms.

Because UTIs are frequently self-limiting, Dr. Scott and others have found that for young, otherwise healthy women, NSAIDs alone can often resolve symptoms of the UTI without use of an antibiotic. For relatively severe symptoms, a urinary analgesic, such as phenazopyridine (Pyridium), may soothe the lining of the urinary tract and relieve pain. Cystex is an over-the-counter urinary analgesic that women can procure themselves, Dr. Scott added.

If an antibiotic is indicated, those most commonly prescribed for a single episode of acute cystitis are nitrofurantoin and sulfamethoxazole plus trimethoprim (Bactrim). For recurrent UTIs, “patients are a bit more complicated,” Dr. Scott admitted. “I think the best practice is to look back at a woman’s prior urine culture and select an antibiotic that showed good sensitivity in the last positive urine test,” she said.

Prevention starts with behavioral strategies, such as voiding after sexual intercourse and wiping from front to back following urination to avoid introducing fecal bacteria into the urethra. Evidence suggests that premenopausal women who drink at least 1.5 L of water a day have significantly fewer UTI episodes, Dr. Scott noted. There is also “pretty good” evidence that cranberry supplements (not juice) can prevent rUTIs. Use of cranberry supplements is supported by the American Urological Association (conditional recommendation; evidence level of grade C).

For peri- and postmenopausal women, vaginal estrogen may be effective. It’s use for UTI prevention is well supported by the literature. Although not as well supported by evidence, some women find that a supplement such as D-mannose may prevent or treat UTIs by causing bacteria to bind to it rather than to the bladder wall. Probiotics are another possibility, she noted. Empathy can’t hurt, she added.

“A common theme among satisfied women was the sentiment that their physicians understood their problems and had a system in place to allow rapid diagnosis and treatment for UTI episodes,” the authors emphasized.

“[Such attitudes] highlight the need to investigate each patient’s experience and perceptions to allow for shared decision making regarding the management of rUTIs,” they wrote.
 

Further commentary

Asked to comment on the findings, editorialist Michelle Van Kuiken, MD, assistant professor of urology, University of California, San Francisco, acknowledged that there is not a lot of good evidence to support many of the strategies recommended by the American Urological Association to prevent and treat rUTIs, but she often follows these recommendations anyway. “The one statement in the guidelines that is the most supported by evidence is the use of cranberry supplements, and I do routinely recommended daily use of some form of concentrated cranberry supplements for all of my patients with rUTIs,” she said in an interview.

Dr. Van Kuiken said that vaginal estrogen is a very good option for all postmenopausal women who suffer from rUTIs and that there is growing acceptance of its use for this and other indications. There is some evidence to support D-mannose as well, although it’s not that robust, she acknowledged.

She said the evidence supporting the use of probiotics for this indication is very thin. She does not routinely recommend them for rUTIs, although they are not inherently harmful. “I think for a lot of women who have rUTIs, it can be pretty debilitating and upsetting for them – it can impact travel plans, work, and social events,” Dr. Van Kuiken said.

“Until we develop better diagnostic and therapeutic strategies, validating women’s experiences and concerns with rUTI while limiting unnecessary antibiotics remains our best option,” she wrote.

Dr. Scott and Dr. Van Kuiken have disclosed no relevant financial relationships.

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

Fear of antibiotic overuse and frustration with physicians who prescribe them too freely are key sentiments expressed by women with recurrent urinary tract infections (rUTIs), according to findings from a study involving six focus groups.

“Here in our female pelvic medicine reconstructive urology clinic at Cedars-Sinai and at UCLA, we see many women who are referred for evaluation of rUTIs who are very frustrated with their care,” Victoria Scott, MD, Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“So with these focus groups, we saw an opportunity to explore why women are so frustrated and to try and improve the care delivered,” she added.

Findings from the study were published online Sept. 1 in The Journal of Urology.

“There is a need for physicians to modify management strategies ... and to devote more research efforts to improving nonantibiotic options for the prevention and treatment of recurrent urinary tract infections, as well as management strategies that better empower patients,” the authors wrote.
 

Six focus groups

Four or five participants were included in each of the six focus groups – a total of 29 women. All participants reported a history of symptomatic, culture-proven UTI episodes. They had experienced two or more infections in 6 months or three or more infections within 1 year. Women were predominantly White. Most were employed part- or full-time and held a college degree.

From a qualitative analysis of all focus group transcripts, two main themes emerged:

• The negative impact of taking antibiotics for the prevention and treatment of rUTIs.
• Resentment of the medical profession for the way it managed rUTIs.

The researchers found that participants had a good understanding of the deleterious effects from inappropriate antibiotic use, largely gleaned from media sources and the Internet. “Numerous women stated that they had reached such a level of concern about antibiotics that they would resist taking them for prevention or treatment of infections,” Dr. Scott and colleagues pointed out.

These concerns centered around the risk of developing resistance to antibiotics and the ill effects that antibiotics can have on the gastrointestinal and genitourinary microbiomes. Several women reported that they had developed Clostridium difficile infections after taking antibiotics; one of the patients required hospitalization for the infection.

Women also reported concerns that they had been given an antibiotic needlessly for symptoms that might have been caused by a genitourinary condition other than a UTI. They also reported feeling resentful toward practitioners, particularly if they felt the practitioner was overprescribing antibiotics. Some had resorted to consultations with alternative practitioners, such as herbalists. “A second concern discussed by participants was the feeling of being ignored by physicians,” the authors observed.

In this regard, the women felt that their physicians underestimated the burden that rUTIs had on their lives and the detrimental effect that repeated infections had on their relationships, work, and overall quality of life. “These perceptions led to a prevalent mistrust of physicians,” the investigators wrote. This prompted many women to insist that the medical community devote more effort to the development of nonantibiotic options for the prevention and treatment of UTIs.
 

Improved management strategies

Asked how physicians might improve their management of rUTIs, Dr. Scott shared a number of suggestions. Cardinal rule No. 1: Have the patient undergo a urinalysis to make sure she does have a UTI. “There is a subset of patients among women with rUTIs who come in with a diagnosis of an rUTI but who really have not had documentation of more than one positive urine culture,” Dr. Scott noted. Such a history suggests that they do not have an rUTI.

It’s imperative that physicians rule out commonly misdiagnosed disorders, such as overactive bladder, as a cause of the patient’s symptoms. Symptoms of overactive bladder and rUTIs often overlap. While waiting for results from the urinalysis to confirm or rule out a UTI, young and healthy women may be prescribed a nonsteroidal anti-inflammatory drug (NSAID), such as naproxen, which can help ameliorate symptoms.

Because UTIs are frequently self-limiting, Dr. Scott and others have found that for young, otherwise healthy women, NSAIDs alone can often resolve symptoms of the UTI without use of an antibiotic. For relatively severe symptoms, a urinary analgesic, such as phenazopyridine (Pyridium), may soothe the lining of the urinary tract and relieve pain. Cystex is an over-the-counter urinary analgesic that women can procure themselves, Dr. Scott added.

If an antibiotic is indicated, those most commonly prescribed for a single episode of acute cystitis are nitrofurantoin and sulfamethoxazole plus trimethoprim (Bactrim). For recurrent UTIs, “patients are a bit more complicated,” Dr. Scott admitted. “I think the best practice is to look back at a woman’s prior urine culture and select an antibiotic that showed good sensitivity in the last positive urine test,” she said.

Prevention starts with behavioral strategies, such as voiding after sexual intercourse and wiping from front to back following urination to avoid introducing fecal bacteria into the urethra. Evidence suggests that premenopausal women who drink at least 1.5 L of water a day have significantly fewer UTI episodes, Dr. Scott noted. There is also “pretty good” evidence that cranberry supplements (not juice) can prevent rUTIs. Use of cranberry supplements is supported by the American Urological Association (conditional recommendation; evidence level of grade C).

For peri- and postmenopausal women, vaginal estrogen may be effective. It’s use for UTI prevention is well supported by the literature. Although not as well supported by evidence, some women find that a supplement such as D-mannose may prevent or treat UTIs by causing bacteria to bind to it rather than to the bladder wall. Probiotics are another possibility, she noted. Empathy can’t hurt, she added.

“A common theme among satisfied women was the sentiment that their physicians understood their problems and had a system in place to allow rapid diagnosis and treatment for UTI episodes,” the authors emphasized.

“[Such attitudes] highlight the need to investigate each patient’s experience and perceptions to allow for shared decision making regarding the management of rUTIs,” they wrote.
 

Further commentary

Asked to comment on the findings, editorialist Michelle Van Kuiken, MD, assistant professor of urology, University of California, San Francisco, acknowledged that there is not a lot of good evidence to support many of the strategies recommended by the American Urological Association to prevent and treat rUTIs, but she often follows these recommendations anyway. “The one statement in the guidelines that is the most supported by evidence is the use of cranberry supplements, and I do routinely recommended daily use of some form of concentrated cranberry supplements for all of my patients with rUTIs,” she said in an interview.

Dr. Van Kuiken said that vaginal estrogen is a very good option for all postmenopausal women who suffer from rUTIs and that there is growing acceptance of its use for this and other indications. There is some evidence to support D-mannose as well, although it’s not that robust, she acknowledged.

She said the evidence supporting the use of probiotics for this indication is very thin. She does not routinely recommend them for rUTIs, although they are not inherently harmful. “I think for a lot of women who have rUTIs, it can be pretty debilitating and upsetting for them – it can impact travel plans, work, and social events,” Dr. Van Kuiken said.

“Until we develop better diagnostic and therapeutic strategies, validating women’s experiences and concerns with rUTI while limiting unnecessary antibiotics remains our best option,” she wrote.

Dr. Scott and Dr. Van Kuiken have disclosed no relevant financial relationships.

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

A secondary consequence of public health measures to prevent the spread of SARS-CoV-2 included a concurrent reduction in risk for children to acquire and spread other respiratory viral infectious diseases. In the Rochester, N.Y., area, we had an ongoing prospective study in primary care pediatric practices that afforded an opportunity to assess the effect of the pandemic control measures on all infectious disease illness visits in young children. Specifically, in children aged 6-36 months old, our study was in place when the pandemic began with a primary objective to evaluate the changing epidemiology of acute otitis media (AOM) and nasopharyngeal colonization by potential bacterial respiratory pathogens in community-based primary care pediatric practices. As the public health measures mandated by New York State Department of Health were implemented, we prospectively quantified their effect on physician-diagnosed infectious disease illness visits. The incidence of infectious disease visits by a cohort of young children during the COVID-19 pandemic period March 15, 2020, through Dec. 31, 2020, was compared with the same time frame in the preceding year, 2019.¹

Recommendations of the New York State Department of Health for public health, changes in school and day care attendance, and clinical practice during the study time frame

On March 7, 2020, a state of emergency was declared in New York because of the COVID-19 pandemic. All schools were required to close. A mandated order for public use of masks in adults and children more than 2 years of age was enacted. In the Finger Lakes region of Upstate New York, where the two primary care pediatric practices reside, complete lockdown was partially lifted on May 15, 2020, and further lifted on June 26, 2020. Almost all regional school districts opened to at least hybrid learning models for all students starting Sept. 8, 2020. On March 6, 2020, video telehealth and telephone call visits were introduced as routine practice. Well-child visits were limited to those less than 2 years of age, then gradually expanded to all ages by late May 2020. During the “stay at home” phase of the New York State lockdown, day care services were considered an essential business. Day care child density was limited. All children less than 2 years old were required to wear a mask while in the facility. Upon arrival, children with any respiratory symptoms or fever were excluded. For the school year commencing September 2020, almost all regional school districts opened to virtual, hybrid, or in-person learning models. Exclusion occurred similar to that of the day care facilities.

Incidence of respiratory infectious disease illnesses

Clinical diagnoses and healthy visits of 144 children from March 15 to Dec. 31, 2020 (beginning of the pandemic) were compared to 215 children during the same months in 2019 (prepandemic). Pediatric SARS-CoV-2 positivity rates trended up alongside community spread. Pediatric practice positivity rates rose from 1.9% in October 2020 to 19% in December 2020.

The table shows the incidence of significantly different infectious disease illness visits in the two study cohorts.

Change in care practices

In the prepandemic period, virtual visits, leading to a diagnosis and treatment and referring children to an urgent care or hospital emergency department during regular office hours were rare. During the pandemic, this changed. Significantly increased use of telemedicine visits (P < .0001) and significantly decreased office and urgent care visits (P < .0001) occurred during the pandemic. Telehealth visits peaked the week of April 12, 2020, at 45% of all pediatric visits. In-person illness visits gradually returned to year-to-year volumes in August-September 2020 with school opening. Early in the pandemic, both pediatric offices limited patient encounters to well-child visits in the first 2 years of life to not miss opportunities for childhood vaccinations. However, some parents were reluctant to bring their children to those visits. There was no significant change in frequency of healthy child visits during the pandemic.

To our knowledge, this was the first study from primary care pediatric practices in the United States to analyze the effect on infectious diseases during the first 9 months of the pandemic, including the 6-month time period after the reopening from the first 3 months of lockdown. One prior study from a primary care network in Massachusetts reported significant decreases in respiratory infectious diseases for children aged 0-17 years during the first months of the pandemic during lockdown.² A study in Tennessee that included hospital emergency department, urgent care, primary care, and retail health clinics also reported respiratory infection diagnoses as well as antibiotic prescription were reduced in the early months of the pandemic.³

Our study shows an overall reduction in frequency of respiratory illness visits in children 6-36 months old during the first 9 months of the COVID-19 pandemic. We learned the value of using technology in the form of virtual visits to render care. Perhaps as the pandemic subsides, many of the hand-washing and sanitizing practices will remain in place and lead to less frequent illness in children in the future. However, there may be temporary negative consequences from the “immune debt” that has occurred from a prolonged time span when children were not becoming infected with respiratory pathogens.⁴ We will see what unfolds in the future.
 

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz is pediatric medical director at Rochester (N.Y.) Regional Health. Dr. Pichichero and Dr. Schulz have no conflicts of interest to disclose. This study was funded in part by the Centers for Disease Control and Prevention.

References

1. Kaur R et al. Front Pediatr. 2021;(9)722483:1-8.

2. Hatoun J et al. Pediatrics. 2020;146(4):e2020006460.

3. Katz SE et al. J Pediatric Infect Dis Soc. 2021;10(1):62-4.

4. Cohen R et al. Infect. Dis Now. 2021; 51(5)418-23.

A secondary consequence of public health measures to prevent the spread of SARS-CoV-2 included a concurrent reduction in risk for children to acquire and spread other respiratory viral infectious diseases. In the Rochester, N.Y., area, we had an ongoing prospective study in primary care pediatric practices that afforded an opportunity to assess the effect of the pandemic control measures on all infectious disease illness visits in young children. Specifically, in children aged 6-36 months old, our study was in place when the pandemic began with a primary objective to evaluate the changing epidemiology of acute otitis media (AOM) and nasopharyngeal colonization by potential bacterial respiratory pathogens in community-based primary care pediatric practices. As the public health measures mandated by New York State Department of Health were implemented, we prospectively quantified their effect on physician-diagnosed infectious disease illness visits. The incidence of infectious disease visits by a cohort of young children during the COVID-19 pandemic period March 15, 2020, through Dec. 31, 2020, was compared with the same time frame in the preceding year, 2019.¹

Recommendations of the New York State Department of Health for public health, changes in school and day care attendance, and clinical practice during the study time frame

On March 7, 2020, a state of emergency was declared in New York because of the COVID-19 pandemic. All schools were required to close. A mandated order for public use of masks in adults and children more than 2 years of age was enacted. In the Finger Lakes region of Upstate New York, where the two primary care pediatric practices reside, complete lockdown was partially lifted on May 15, 2020, and further lifted on June 26, 2020. Almost all regional school districts opened to at least hybrid learning models for all students starting Sept. 8, 2020. On March 6, 2020, video telehealth and telephone call visits were introduced as routine practice. Well-child visits were limited to those less than 2 years of age, then gradually expanded to all ages by late May 2020. During the “stay at home” phase of the New York State lockdown, day care services were considered an essential business. Day care child density was limited. All children less than 2 years old were required to wear a mask while in the facility. Upon arrival, children with any respiratory symptoms or fever were excluded. For the school year commencing September 2020, almost all regional school districts opened to virtual, hybrid, or in-person learning models. Exclusion occurred similar to that of the day care facilities.

Incidence of respiratory infectious disease illnesses

Clinical diagnoses and healthy visits of 144 children from March 15 to Dec. 31, 2020 (beginning of the pandemic) were compared to 215 children during the same months in 2019 (prepandemic). Pediatric SARS-CoV-2 positivity rates trended up alongside community spread. Pediatric practice positivity rates rose from 1.9% in October 2020 to 19% in December 2020.

The table shows the incidence of significantly different infectious disease illness visits in the two study cohorts.

Change in care practices

In the prepandemic period, virtual visits, leading to a diagnosis and treatment and referring children to an urgent care or hospital emergency department during regular office hours were rare. During the pandemic, this changed. Significantly increased use of telemedicine visits (P < .0001) and significantly decreased office and urgent care visits (P < .0001) occurred during the pandemic. Telehealth visits peaked the week of April 12, 2020, at 45% of all pediatric visits. In-person illness visits gradually returned to year-to-year volumes in August-September 2020 with school opening. Early in the pandemic, both pediatric offices limited patient encounters to well-child visits in the first 2 years of life to not miss opportunities for childhood vaccinations. However, some parents were reluctant to bring their children to those visits. There was no significant change in frequency of healthy child visits during the pandemic.

To our knowledge, this was the first study from primary care pediatric practices in the United States to analyze the effect on infectious diseases during the first 9 months of the pandemic, including the 6-month time period after the reopening from the first 3 months of lockdown. One prior study from a primary care network in Massachusetts reported significant decreases in respiratory infectious diseases for children aged 0-17 years during the first months of the pandemic during lockdown.² A study in Tennessee that included hospital emergency department, urgent care, primary care, and retail health clinics also reported respiratory infection diagnoses as well as antibiotic prescription were reduced in the early months of the pandemic.³

Our study shows an overall reduction in frequency of respiratory illness visits in children 6-36 months old during the first 9 months of the COVID-19 pandemic. We learned the value of using technology in the form of virtual visits to render care. Perhaps as the pandemic subsides, many of the hand-washing and sanitizing practices will remain in place and lead to less frequent illness in children in the future. However, there may be temporary negative consequences from the “immune debt” that has occurred from a prolonged time span when children were not becoming infected with respiratory pathogens.⁴ We will see what unfolds in the future.
 

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz is pediatric medical director at Rochester (N.Y.) Regional Health. Dr. Pichichero and Dr. Schulz have no conflicts of interest to disclose. This study was funded in part by the Centers for Disease Control and Prevention.

References

1. Kaur R et al. Front Pediatr. 2021;(9)722483:1-8.

2. Hatoun J et al. Pediatrics. 2020;146(4):e2020006460.

3. Katz SE et al. J Pediatric Infect Dis Soc. 2021;10(1):62-4.

4. Cohen R et al. Infect. Dis Now. 2021; 51(5)418-23.

A secondary consequence of public health measures to prevent the spread of SARS-CoV-2 included a concurrent reduction in risk for children to acquire and spread other respiratory viral infectious diseases. In the Rochester, N.Y., area, we had an ongoing prospective study in primary care pediatric practices that afforded an opportunity to assess the effect of the pandemic control measures on all infectious disease illness visits in young children. Specifically, in children aged 6-36 months old, our study was in place when the pandemic began with a primary objective to evaluate the changing epidemiology of acute otitis media (AOM) and nasopharyngeal colonization by potential bacterial respiratory pathogens in community-based primary care pediatric practices. As the public health measures mandated by New York State Department of Health were implemented, we prospectively quantified their effect on physician-diagnosed infectious disease illness visits. The incidence of infectious disease visits by a cohort of young children during the COVID-19 pandemic period March 15, 2020, through Dec. 31, 2020, was compared with the same time frame in the preceding year, 2019.¹

Recommendations of the New York State Department of Health for public health, changes in school and day care attendance, and clinical practice during the study time frame

On March 7, 2020, a state of emergency was declared in New York because of the COVID-19 pandemic. All schools were required to close. A mandated order for public use of masks in adults and children more than 2 years of age was enacted. In the Finger Lakes region of Upstate New York, where the two primary care pediatric practices reside, complete lockdown was partially lifted on May 15, 2020, and further lifted on June 26, 2020. Almost all regional school districts opened to at least hybrid learning models for all students starting Sept. 8, 2020. On March 6, 2020, video telehealth and telephone call visits were introduced as routine practice. Well-child visits were limited to those less than 2 years of age, then gradually expanded to all ages by late May 2020. During the “stay at home” phase of the New York State lockdown, day care services were considered an essential business. Day care child density was limited. All children less than 2 years old were required to wear a mask while in the facility. Upon arrival, children with any respiratory symptoms or fever were excluded. For the school year commencing September 2020, almost all regional school districts opened to virtual, hybrid, or in-person learning models. Exclusion occurred similar to that of the day care facilities.

Incidence of respiratory infectious disease illnesses

Clinical diagnoses and healthy visits of 144 children from March 15 to Dec. 31, 2020 (beginning of the pandemic) were compared to 215 children during the same months in 2019 (prepandemic). Pediatric SARS-CoV-2 positivity rates trended up alongside community spread. Pediatric practice positivity rates rose from 1.9% in October 2020 to 19% in December 2020.

The table shows the incidence of significantly different infectious disease illness visits in the two study cohorts.

Change in care practices

In the prepandemic period, virtual visits, leading to a diagnosis and treatment and referring children to an urgent care or hospital emergency department during regular office hours were rare. During the pandemic, this changed. Significantly increased use of telemedicine visits (P < .0001) and significantly decreased office and urgent care visits (P < .0001) occurred during the pandemic. Telehealth visits peaked the week of April 12, 2020, at 45% of all pediatric visits. In-person illness visits gradually returned to year-to-year volumes in August-September 2020 with school opening. Early in the pandemic, both pediatric offices limited patient encounters to well-child visits in the first 2 years of life to not miss opportunities for childhood vaccinations. However, some parents were reluctant to bring their children to those visits. There was no significant change in frequency of healthy child visits during the pandemic.

To our knowledge, this was the first study from primary care pediatric practices in the United States to analyze the effect on infectious diseases during the first 9 months of the pandemic, including the 6-month time period after the reopening from the first 3 months of lockdown. One prior study from a primary care network in Massachusetts reported significant decreases in respiratory infectious diseases for children aged 0-17 years during the first months of the pandemic during lockdown.² A study in Tennessee that included hospital emergency department, urgent care, primary care, and retail health clinics also reported respiratory infection diagnoses as well as antibiotic prescription were reduced in the early months of the pandemic.³

Our study shows an overall reduction in frequency of respiratory illness visits in children 6-36 months old during the first 9 months of the COVID-19 pandemic. We learned the value of using technology in the form of virtual visits to render care. Perhaps as the pandemic subsides, many of the hand-washing and sanitizing practices will remain in place and lead to less frequent illness in children in the future. However, there may be temporary negative consequences from the “immune debt” that has occurred from a prolonged time span when children were not becoming infected with respiratory pathogens.⁴ We will see what unfolds in the future.
 

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. Dr. Schulz is pediatric medical director at Rochester (N.Y.) Regional Health. Dr. Pichichero and Dr. Schulz have no conflicts of interest to disclose. This study was funded in part by the Centers for Disease Control and Prevention.

References

1. Kaur R et al. Front Pediatr. 2021;(9)722483:1-8.

2. Hatoun J et al. Pediatrics. 2020;146(4):e2020006460.

3. Katz SE et al. J Pediatric Infect Dis Soc. 2021;10(1):62-4.

4. Cohen R et al. Infect. Dis Now. 2021; 51(5)418-23.

High-efficiency particulate air (HEPA) filters and ultraviolet (UV) light sterilization effectively remove SARS-CoV-2 particles from the air — the first such evidence in a real-world test, researchers report in the preprint server medRxiv.

The journal Nature reported Oct. 6 that the research, which has not been peer-reviewed, suggests the filters may help reduce the risk of hospital-acquired SARS-CoV-2.

Researchers, led by intensivist Andrew Conway-Morris, MBChB, PhD, with the division of anaesthesia in the school of clinical medicine at University of Cambridge, United Kingdom, write that earlier experiments assessed air filters’ ability to remove inactive particles in carefully controlled environments, but it was unknown how they would work in a real-world setting.

Co-author Vilas Navapurkar, MBChB, an ICU physician at Addenbrooke’s Hospital in Cambridge, United Kingdom, said that hospitals have used portable air filters when their isolation facilities are full, but evidence was needed as to whether such filters are effective or whether they provide a false sense of security.

The researchers installed the filters in two fully occupied COVID-19 wards — a general ward and an ICU. They chose HEPA filters because they can catch extremely small particles.

The team collected air samples from the wards during a week when the air filters were on and 2 weeks when they were turned off, then compared results.

According to the study, “airborne SARS-CoV-2 was detected in the ward on all five days before activation of air/UV filtration, but on none of the five days when the air/UV filter was operational; SARS-CoV-2 was again detected on four out of five days when the filter was off.”

Airborne SARS-CoV-2 was not frequently detected in the ICU, even when the filters were off.

Cheap and easy

According to the Nature article, the authors suggest several potential explanations for this, “including slower viral replication at later stages of the disease.” Therefore, the authors say, filtering the virus from the air might be more important in general wards than in ICUs.

The filters significantly reduced the other microbial bioaerosols in both the ward (48 pathogens detected before filtration, 2 after, P = .05) and the ICU (45 pathogens detected before filtration, 5 after P = .05).

National Institute for Occupational Safety and Health (NIOSH) cyclonic aerosol samplers and PCR tests were used to detect airborne SARS-CoV-2 and other microbial bioaerosol.

David Fisman, MD, an epidemiologist at the University of Toronto, who was not involved in the research, said in the Nature article, “This study suggests that HEPA air cleaners, which remain little-used in Canadian hospitals, are a cheap and easy way to reduce risk from airborne pathogens.”This work was supported by a Wellcome senior research fellowship to co-author Stephen Baker. Conway Morris is supported by a Clinician Scientist Fellowship from the Medical Research Council. Dr. Navapurkar is the founder, director, and shareholder of Cambridge Infection Diagnostics Ltd. Dr. Conway-Morris and several co-authors are members of the Scientific Advisory Board of Cambridge Infection Diagnostics Ltd. Co-author Theodore Gouliouris has received a research grant from Shionogi and co-author R. Andres Floto has received research grants and/or consultancy payments from GSK, AstraZeneca, Chiesi, Shionogi, Insmed, and Thirty Technology.

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

High-efficiency particulate air (HEPA) filters and ultraviolet (UV) light sterilization effectively remove SARS-CoV-2 particles from the air — the first such evidence in a real-world test, researchers report in the preprint server medRxiv.

The journal Nature reported Oct. 6 that the research, which has not been peer-reviewed, suggests the filters may help reduce the risk of hospital-acquired SARS-CoV-2.

Researchers, led by intensivist Andrew Conway-Morris, MBChB, PhD, with the division of anaesthesia in the school of clinical medicine at University of Cambridge, United Kingdom, write that earlier experiments assessed air filters’ ability to remove inactive particles in carefully controlled environments, but it was unknown how they would work in a real-world setting.

Co-author Vilas Navapurkar, MBChB, an ICU physician at Addenbrooke’s Hospital in Cambridge, United Kingdom, said that hospitals have used portable air filters when their isolation facilities are full, but evidence was needed as to whether such filters are effective or whether they provide a false sense of security.

The researchers installed the filters in two fully occupied COVID-19 wards — a general ward and an ICU. They chose HEPA filters because they can catch extremely small particles.

The team collected air samples from the wards during a week when the air filters were on and 2 weeks when they were turned off, then compared results.

According to the study, “airborne SARS-CoV-2 was detected in the ward on all five days before activation of air/UV filtration, but on none of the five days when the air/UV filter was operational; SARS-CoV-2 was again detected on four out of five days when the filter was off.”

Airborne SARS-CoV-2 was not frequently detected in the ICU, even when the filters were off.

Cheap and easy

According to the Nature article, the authors suggest several potential explanations for this, “including slower viral replication at later stages of the disease.” Therefore, the authors say, filtering the virus from the air might be more important in general wards than in ICUs.

The filters significantly reduced the other microbial bioaerosols in both the ward (48 pathogens detected before filtration, 2 after, P = .05) and the ICU (45 pathogens detected before filtration, 5 after P = .05).

National Institute for Occupational Safety and Health (NIOSH) cyclonic aerosol samplers and PCR tests were used to detect airborne SARS-CoV-2 and other microbial bioaerosol.

David Fisman, MD, an epidemiologist at the University of Toronto, who was not involved in the research, said in the Nature article, “This study suggests that HEPA air cleaners, which remain little-used in Canadian hospitals, are a cheap and easy way to reduce risk from airborne pathogens.”This work was supported by a Wellcome senior research fellowship to co-author Stephen Baker. Conway Morris is supported by a Clinician Scientist Fellowship from the Medical Research Council. Dr. Navapurkar is the founder, director, and shareholder of Cambridge Infection Diagnostics Ltd. Dr. Conway-Morris and several co-authors are members of the Scientific Advisory Board of Cambridge Infection Diagnostics Ltd. Co-author Theodore Gouliouris has received a research grant from Shionogi and co-author R. Andres Floto has received research grants and/or consultancy payments from GSK, AstraZeneca, Chiesi, Shionogi, Insmed, and Thirty Technology.

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

High-efficiency particulate air (HEPA) filters and ultraviolet (UV) light sterilization effectively remove SARS-CoV-2 particles from the air — the first such evidence in a real-world test, researchers report in the preprint server medRxiv.

The journal Nature reported Oct. 6 that the research, which has not been peer-reviewed, suggests the filters may help reduce the risk of hospital-acquired SARS-CoV-2.

Researchers, led by intensivist Andrew Conway-Morris, MBChB, PhD, with the division of anaesthesia in the school of clinical medicine at University of Cambridge, United Kingdom, write that earlier experiments assessed air filters’ ability to remove inactive particles in carefully controlled environments, but it was unknown how they would work in a real-world setting.

Co-author Vilas Navapurkar, MBChB, an ICU physician at Addenbrooke’s Hospital in Cambridge, United Kingdom, said that hospitals have used portable air filters when their isolation facilities are full, but evidence was needed as to whether such filters are effective or whether they provide a false sense of security.

The researchers installed the filters in two fully occupied COVID-19 wards — a general ward and an ICU. They chose HEPA filters because they can catch extremely small particles.

The team collected air samples from the wards during a week when the air filters were on and 2 weeks when they were turned off, then compared results.

According to the study, “airborne SARS-CoV-2 was detected in the ward on all five days before activation of air/UV filtration, but on none of the five days when the air/UV filter was operational; SARS-CoV-2 was again detected on four out of five days when the filter was off.”

Airborne SARS-CoV-2 was not frequently detected in the ICU, even when the filters were off.

Cheap and easy

According to the Nature article, the authors suggest several potential explanations for this, “including slower viral replication at later stages of the disease.” Therefore, the authors say, filtering the virus from the air might be more important in general wards than in ICUs.

The filters significantly reduced the other microbial bioaerosols in both the ward (48 pathogens detected before filtration, 2 after, P = .05) and the ICU (45 pathogens detected before filtration, 5 after P = .05).

National Institute for Occupational Safety and Health (NIOSH) cyclonic aerosol samplers and PCR tests were used to detect airborne SARS-CoV-2 and other microbial bioaerosol.

David Fisman, MD, an epidemiologist at the University of Toronto, who was not involved in the research, said in the Nature article, “This study suggests that HEPA air cleaners, which remain little-used in Canadian hospitals, are a cheap and easy way to reduce risk from airborne pathogens.”This work was supported by a Wellcome senior research fellowship to co-author Stephen Baker. Conway Morris is supported by a Clinician Scientist Fellowship from the Medical Research Council. Dr. Navapurkar is the founder, director, and shareholder of Cambridge Infection Diagnostics Ltd. Dr. Conway-Morris and several co-authors are members of the Scientific Advisory Board of Cambridge Infection Diagnostics Ltd. Co-author Theodore Gouliouris has received a research grant from Shionogi and co-author R. Andres Floto has received research grants and/or consultancy payments from GSK, AstraZeneca, Chiesi, Shionogi, Insmed, and Thirty Technology.

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