Heidi Splete

Boys exposed to at least 2 hours a day of screen time by 1 year of age were significantly more likely to have an autism spectrum disorder (ASD) diagnosis at 3 years, based on data from more than 80,000 children.

The World Health Organization and the American Academy of Pediatrics recommend against any screen time for infants up to 1 year of age and 18 months of age, respectively, wrote Megumi Kushima, MA, of the University of Yamanashi (Japan), and colleagues on behalf of the Japan Environment and Children’s Study Group.

The extent to which screen time duration in infancy is associated with subsequent ASD diagnosis remains unclear, the researchers said. The ongoing COVID-19 pandemic has increased screen time among children worldwide, which makes an examination of the impact of screen time on children’s health an important public health issue.

In a study published in JAMA Pediatrics, the researchers recruited pregnant women between 2011 and 2014; data were analyzed in December 2020. The final study population included 84,030 mother-child pairs. The primary exposure of screen time at 1 year of age was assessed by questionnaire, in which mothers were asked to report their number of hours they let their child watch TV or DVDs daily. Responses were none (no screen time), less than 1 hour, 1 hour or more but less than 2 hours, 2 hours or more but less than 4 hours, and 4 hours or more.

The primary outcome was ASD diagnosis at 3 years of age, and mothers were asked via questionnaire whether their 3-year-old had been diagnosed with ASD from age 2.

The study was conducted by the Japan Environment and Children’s Study Group at 15 regional centers across Japan.

Overall, 330 children had received an ASD diagnosis at age 3 years, a prevalence of 0.4%. Of these, 251 (76%) were boys, and 79 (24%) were girls. Independent of ASD, the most common response for screen time was less than 1 hour, which was reported by 27,707 mothers. The proportion of children with ASD at age 3 increased as screen time at age 1 increased, the percentages were 5.8%, 22.3%, 30.2%, and 31.7% for children with no screen time, less than 1 hour, 1 to less than 2 hours, and 2 to less than 4 hours, respectively. The percentage of children with ASD diagnoses who had 4 hours or more of daily screen time was 10%.

Logistic regression analysis showed that longer screen time at age 1 year was significantly associated with higher odds of ASD at 3 years in boys, but not in girls. The researchers controlled for variables including maternal maltreatment and children’s predisposition to ASD. Among boys, the adjusted odds ratios for screen times of less than 1 hour, 1 hour to less than 2 hours, 2 hours to less than 4 hours, and more than 4 hours were 1.38, 2.16, 3.48, and 3.02, respectively.

Screen time at age 3 years was not associated with ASD diagnosis at age 3 years, potentially “because the association with environmental factors on brain development varies with age,” the researchers noted.

The study findings were limited by several factors including the reliance on parental reports of screen time and potential for reporting bias, the researchers noted. Other limitations included the possible missed diagnoses of mild ASD cases at 3 years, and the inability to consider variables such as childcare environment, living conditions, diseases, genetics, and disabilities.

However, the results were strengthened by the large study population and examination of screen time in early childhood, they said. More research is needed to examine other factors that contribute to the association between ASD and screen time, but given the rapid increase in device use in children, “it is necessary to review its health effects on infants and control excessive screen time.”
 

Strong study, but some gaps appear

The study is strong in many respects, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

However, “what I am not sure they addressed is that children on the spectrum are often not entertained by basic toys and may be hard to manage behaviorally,” Dr. Kinsella said. Consequently, parents may be more inclined to offer screen time as a way to pacify children with behavioral difficulties. “Parents also may see that their children are happier interacting with devices, so they may be more apt to let them continue with screen time.We know screen time is not good for the developing brain, however; I worry that the message from this study is that screen time causes autism in boys.

“What I would have liked to know from the parents who allowed more screen time was why they were offering it,” Dr. Kinsella said. “Was it because their child was difficult behaviorally or because that is the one place that they seemed to have satisfaction? To me, that would indicate the reverse hypothesis.” That said, the study findings “remind us to counsel families about screen time, especially in the age of COVID-19. Kids are home much longer than usual, which ultimately leads to more screen time.”

The study was funded by the Japanese Ministry of Environment. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.

Boys exposed to at least 2 hours a day of screen time by 1 year of age were significantly more likely to have an autism spectrum disorder (ASD) diagnosis at 3 years, based on data from more than 80,000 children.

The World Health Organization and the American Academy of Pediatrics recommend against any screen time for infants up to 1 year of age and 18 months of age, respectively, wrote Megumi Kushima, MA, of the University of Yamanashi (Japan), and colleagues on behalf of the Japan Environment and Children’s Study Group.

The extent to which screen time duration in infancy is associated with subsequent ASD diagnosis remains unclear, the researchers said. The ongoing COVID-19 pandemic has increased screen time among children worldwide, which makes an examination of the impact of screen time on children’s health an important public health issue.

In a study published in JAMA Pediatrics, the researchers recruited pregnant women between 2011 and 2014; data were analyzed in December 2020. The final study population included 84,030 mother-child pairs. The primary exposure of screen time at 1 year of age was assessed by questionnaire, in which mothers were asked to report their number of hours they let their child watch TV or DVDs daily. Responses were none (no screen time), less than 1 hour, 1 hour or more but less than 2 hours, 2 hours or more but less than 4 hours, and 4 hours or more.

The primary outcome was ASD diagnosis at 3 years of age, and mothers were asked via questionnaire whether their 3-year-old had been diagnosed with ASD from age 2.

The study was conducted by the Japan Environment and Children’s Study Group at 15 regional centers across Japan.

Overall, 330 children had received an ASD diagnosis at age 3 years, a prevalence of 0.4%. Of these, 251 (76%) were boys, and 79 (24%) were girls. Independent of ASD, the most common response for screen time was less than 1 hour, which was reported by 27,707 mothers. The proportion of children with ASD at age 3 increased as screen time at age 1 increased, the percentages were 5.8%, 22.3%, 30.2%, and 31.7% for children with no screen time, less than 1 hour, 1 to less than 2 hours, and 2 to less than 4 hours, respectively. The percentage of children with ASD diagnoses who had 4 hours or more of daily screen time was 10%.

Logistic regression analysis showed that longer screen time at age 1 year was significantly associated with higher odds of ASD at 3 years in boys, but not in girls. The researchers controlled for variables including maternal maltreatment and children’s predisposition to ASD. Among boys, the adjusted odds ratios for screen times of less than 1 hour, 1 hour to less than 2 hours, 2 hours to less than 4 hours, and more than 4 hours were 1.38, 2.16, 3.48, and 3.02, respectively.

Screen time at age 3 years was not associated with ASD diagnosis at age 3 years, potentially “because the association with environmental factors on brain development varies with age,” the researchers noted.

The study findings were limited by several factors including the reliance on parental reports of screen time and potential for reporting bias, the researchers noted. Other limitations included the possible missed diagnoses of mild ASD cases at 3 years, and the inability to consider variables such as childcare environment, living conditions, diseases, genetics, and disabilities.

However, the results were strengthened by the large study population and examination of screen time in early childhood, they said. More research is needed to examine other factors that contribute to the association between ASD and screen time, but given the rapid increase in device use in children, “it is necessary to review its health effects on infants and control excessive screen time.”
 

Strong study, but some gaps appear

The study is strong in many respects, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

However, “what I am not sure they addressed is that children on the spectrum are often not entertained by basic toys and may be hard to manage behaviorally,” Dr. Kinsella said. Consequently, parents may be more inclined to offer screen time as a way to pacify children with behavioral difficulties. “Parents also may see that their children are happier interacting with devices, so they may be more apt to let them continue with screen time.We know screen time is not good for the developing brain, however; I worry that the message from this study is that screen time causes autism in boys.

“What I would have liked to know from the parents who allowed more screen time was why they were offering it,” Dr. Kinsella said. “Was it because their child was difficult behaviorally or because that is the one place that they seemed to have satisfaction? To me, that would indicate the reverse hypothesis.” That said, the study findings “remind us to counsel families about screen time, especially in the age of COVID-19. Kids are home much longer than usual, which ultimately leads to more screen time.”

The study was funded by the Japanese Ministry of Environment. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.

Boys exposed to at least 2 hours a day of screen time by 1 year of age were significantly more likely to have an autism spectrum disorder (ASD) diagnosis at 3 years, based on data from more than 80,000 children.

The World Health Organization and the American Academy of Pediatrics recommend against any screen time for infants up to 1 year of age and 18 months of age, respectively, wrote Megumi Kushima, MA, of the University of Yamanashi (Japan), and colleagues on behalf of the Japan Environment and Children’s Study Group.

The extent to which screen time duration in infancy is associated with subsequent ASD diagnosis remains unclear, the researchers said. The ongoing COVID-19 pandemic has increased screen time among children worldwide, which makes an examination of the impact of screen time on children’s health an important public health issue.

In a study published in JAMA Pediatrics, the researchers recruited pregnant women between 2011 and 2014; data were analyzed in December 2020. The final study population included 84,030 mother-child pairs. The primary exposure of screen time at 1 year of age was assessed by questionnaire, in which mothers were asked to report their number of hours they let their child watch TV or DVDs daily. Responses were none (no screen time), less than 1 hour, 1 hour or more but less than 2 hours, 2 hours or more but less than 4 hours, and 4 hours or more.

The primary outcome was ASD diagnosis at 3 years of age, and mothers were asked via questionnaire whether their 3-year-old had been diagnosed with ASD from age 2.

The study was conducted by the Japan Environment and Children’s Study Group at 15 regional centers across Japan.

Overall, 330 children had received an ASD diagnosis at age 3 years, a prevalence of 0.4%. Of these, 251 (76%) were boys, and 79 (24%) were girls. Independent of ASD, the most common response for screen time was less than 1 hour, which was reported by 27,707 mothers. The proportion of children with ASD at age 3 increased as screen time at age 1 increased, the percentages were 5.8%, 22.3%, 30.2%, and 31.7% for children with no screen time, less than 1 hour, 1 to less than 2 hours, and 2 to less than 4 hours, respectively. The percentage of children with ASD diagnoses who had 4 hours or more of daily screen time was 10%.

Logistic regression analysis showed that longer screen time at age 1 year was significantly associated with higher odds of ASD at 3 years in boys, but not in girls. The researchers controlled for variables including maternal maltreatment and children’s predisposition to ASD. Among boys, the adjusted odds ratios for screen times of less than 1 hour, 1 hour to less than 2 hours, 2 hours to less than 4 hours, and more than 4 hours were 1.38, 2.16, 3.48, and 3.02, respectively.

Screen time at age 3 years was not associated with ASD diagnosis at age 3 years, potentially “because the association with environmental factors on brain development varies with age,” the researchers noted.

The study findings were limited by several factors including the reliance on parental reports of screen time and potential for reporting bias, the researchers noted. Other limitations included the possible missed diagnoses of mild ASD cases at 3 years, and the inability to consider variables such as childcare environment, living conditions, diseases, genetics, and disabilities.

However, the results were strengthened by the large study population and examination of screen time in early childhood, they said. More research is needed to examine other factors that contribute to the association between ASD and screen time, but given the rapid increase in device use in children, “it is necessary to review its health effects on infants and control excessive screen time.”
 

Strong study, but some gaps appear

The study is strong in many respects, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

However, “what I am not sure they addressed is that children on the spectrum are often not entertained by basic toys and may be hard to manage behaviorally,” Dr. Kinsella said. Consequently, parents may be more inclined to offer screen time as a way to pacify children with behavioral difficulties. “Parents also may see that their children are happier interacting with devices, so they may be more apt to let them continue with screen time.We know screen time is not good for the developing brain, however; I worry that the message from this study is that screen time causes autism in boys.

“What I would have liked to know from the parents who allowed more screen time was why they were offering it,” Dr. Kinsella said. “Was it because their child was difficult behaviorally or because that is the one place that they seemed to have satisfaction? To me, that would indicate the reverse hypothesis.” That said, the study findings “remind us to counsel families about screen time, especially in the age of COVID-19. Kids are home much longer than usual, which ultimately leads to more screen time.”

The study was funded by the Japanese Ministry of Environment. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose, but serves as a member of the Pediatric News editorial advisory board.

Hospitalized intensive care patients with respiratory syncytial virus were significantly more likely to be immunocompromised and to have chronic respiratory conditions than those with influenza infections, but in-hospital mortality rates were similar, based on data from 618 adults.

Respiratory syncytial virus is common in adults, but characteristics of RSV patients requiring ICU care have not been explored, despite routine testing for RSV in critically ill patients in many institutions, Julien Coussement, PhD, of Université Libre de Bruxelles, Brussels, and colleagues wrote.

“Influenza is another respiratory virus routinely tested for in ICU patients with respiratory symptoms because of its well-known morbidity and mortality, but there are no data specifically comparing RSV and influenza infections in adult ICU patients,” they noted.

In a retrospective, multicenter study published in the journal CHEST, the researchers analyzed data from 309 adult ICU patients with RSV infection and 309 with influenza infection between November 2011 and April 2018 from 17 sites in France and Belgium. Each RSV patient was matched to a flu patient according to institution and date of diagnosis.

The primary objective was a comparison of in-hospital mortality between the groups, defined as death from any cause during an index hospital stay in acute care. Secondary objectives were comparisons of the clinical and biological characteristics of patients with RSV versus flu.

Overall, in-hospital mortality was not significantly different between the RSV and influenza groups (23.9% vs. 25.6%, P = .63).

However, patients with RSV infection were significantly more likely than those with flu to have an underlying chronic respiratory condition (60.2% vs. 40.1%, P < .001) and to be immunocompromised (35% vs. 26.2%, P = .02). Very few of the patients overall (39 patients, 6.3%) were considered young and healthy prior to hospitalization; and significantly fewer of these were in the RSV group than in the influenza group (9 patients and 30 patients, respectively).

Airway obstruction at the time of diagnosis was significantly more common in the RSV patients than in influenza patients (49.5% vs. 39.5%, P = .01), but influenza patients were significantly more likely to have acute respiratory distress syndrome at the time of diagnosis (21.7% vs. 14.6%, P = .02). Rates of coinfections were similar between the groups, and approximately 60% of coinfected patients received at least 72 hours of therapeutic antibiotics. Overall length of hospital stay, ICU stay, and duration of mechanical ventilation were similar between the groups.

The results show that severe RSV occurs mainly in older patients with comorbidities, and these results reflect data from previous studies, the researchers wrote in their discussion. In addition, “patients with influenza infection were significantly more likely to have fever, myalgia, increased CPK level, thrombocytopenia and transaminitis at diagnosis than were those with RSV infection. Whether these differences may be used to guide patient management remains to be determined.”

The study findings were limited by several factors including the retrospective design, and testing for respiratory viruses on symptomatic patients only, rather than all ICU patients, the researchers noted. Other limitations include the inability to show a causal link between viral infections and patient outcomes and the heterogenous management of patients among different centers.

However, the results were strengthened by the large sample size and multivariate analysis, and support the need for interventions to prevent and treat severe RSV, they concluded.

The study received no outside funding. Lead author Dr. Coussement disclosed serving on advisory board for Sanofi.

Hospitalized intensive care patients with respiratory syncytial virus were significantly more likely to be immunocompromised and to have chronic respiratory conditions than those with influenza infections, but in-hospital mortality rates were similar, based on data from 618 adults.

Respiratory syncytial virus is common in adults, but characteristics of RSV patients requiring ICU care have not been explored, despite routine testing for RSV in critically ill patients in many institutions, Julien Coussement, PhD, of Université Libre de Bruxelles, Brussels, and colleagues wrote.

“Influenza is another respiratory virus routinely tested for in ICU patients with respiratory symptoms because of its well-known morbidity and mortality, but there are no data specifically comparing RSV and influenza infections in adult ICU patients,” they noted.

In a retrospective, multicenter study published in the journal CHEST, the researchers analyzed data from 309 adult ICU patients with RSV infection and 309 with influenza infection between November 2011 and April 2018 from 17 sites in France and Belgium. Each RSV patient was matched to a flu patient according to institution and date of diagnosis.

The primary objective was a comparison of in-hospital mortality between the groups, defined as death from any cause during an index hospital stay in acute care. Secondary objectives were comparisons of the clinical and biological characteristics of patients with RSV versus flu.

Overall, in-hospital mortality was not significantly different between the RSV and influenza groups (23.9% vs. 25.6%, P = .63).

However, patients with RSV infection were significantly more likely than those with flu to have an underlying chronic respiratory condition (60.2% vs. 40.1%, P < .001) and to be immunocompromised (35% vs. 26.2%, P = .02). Very few of the patients overall (39 patients, 6.3%) were considered young and healthy prior to hospitalization; and significantly fewer of these were in the RSV group than in the influenza group (9 patients and 30 patients, respectively).

Airway obstruction at the time of diagnosis was significantly more common in the RSV patients than in influenza patients (49.5% vs. 39.5%, P = .01), but influenza patients were significantly more likely to have acute respiratory distress syndrome at the time of diagnosis (21.7% vs. 14.6%, P = .02). Rates of coinfections were similar between the groups, and approximately 60% of coinfected patients received at least 72 hours of therapeutic antibiotics. Overall length of hospital stay, ICU stay, and duration of mechanical ventilation were similar between the groups.

The results show that severe RSV occurs mainly in older patients with comorbidities, and these results reflect data from previous studies, the researchers wrote in their discussion. In addition, “patients with influenza infection were significantly more likely to have fever, myalgia, increased CPK level, thrombocytopenia and transaminitis at diagnosis than were those with RSV infection. Whether these differences may be used to guide patient management remains to be determined.”

The study findings were limited by several factors including the retrospective design, and testing for respiratory viruses on symptomatic patients only, rather than all ICU patients, the researchers noted. Other limitations include the inability to show a causal link between viral infections and patient outcomes and the heterogenous management of patients among different centers.

However, the results were strengthened by the large sample size and multivariate analysis, and support the need for interventions to prevent and treat severe RSV, they concluded.

The study received no outside funding. Lead author Dr. Coussement disclosed serving on advisory board for Sanofi.

Hospitalized intensive care patients with respiratory syncytial virus were significantly more likely to be immunocompromised and to have chronic respiratory conditions than those with influenza infections, but in-hospital mortality rates were similar, based on data from 618 adults.

Respiratory syncytial virus is common in adults, but characteristics of RSV patients requiring ICU care have not been explored, despite routine testing for RSV in critically ill patients in many institutions, Julien Coussement, PhD, of Université Libre de Bruxelles, Brussels, and colleagues wrote.

“Influenza is another respiratory virus routinely tested for in ICU patients with respiratory symptoms because of its well-known morbidity and mortality, but there are no data specifically comparing RSV and influenza infections in adult ICU patients,” they noted.

In a retrospective, multicenter study published in the journal CHEST, the researchers analyzed data from 309 adult ICU patients with RSV infection and 309 with influenza infection between November 2011 and April 2018 from 17 sites in France and Belgium. Each RSV patient was matched to a flu patient according to institution and date of diagnosis.

The primary objective was a comparison of in-hospital mortality between the groups, defined as death from any cause during an index hospital stay in acute care. Secondary objectives were comparisons of the clinical and biological characteristics of patients with RSV versus flu.

Overall, in-hospital mortality was not significantly different between the RSV and influenza groups (23.9% vs. 25.6%, P = .63).

However, patients with RSV infection were significantly more likely than those with flu to have an underlying chronic respiratory condition (60.2% vs. 40.1%, P < .001) and to be immunocompromised (35% vs. 26.2%, P = .02). Very few of the patients overall (39 patients, 6.3%) were considered young and healthy prior to hospitalization; and significantly fewer of these were in the RSV group than in the influenza group (9 patients and 30 patients, respectively).

Airway obstruction at the time of diagnosis was significantly more common in the RSV patients than in influenza patients (49.5% vs. 39.5%, P = .01), but influenza patients were significantly more likely to have acute respiratory distress syndrome at the time of diagnosis (21.7% vs. 14.6%, P = .02). Rates of coinfections were similar between the groups, and approximately 60% of coinfected patients received at least 72 hours of therapeutic antibiotics. Overall length of hospital stay, ICU stay, and duration of mechanical ventilation were similar between the groups.

The results show that severe RSV occurs mainly in older patients with comorbidities, and these results reflect data from previous studies, the researchers wrote in their discussion. In addition, “patients with influenza infection were significantly more likely to have fever, myalgia, increased CPK level, thrombocytopenia and transaminitis at diagnosis than were those with RSV infection. Whether these differences may be used to guide patient management remains to be determined.”

The study findings were limited by several factors including the retrospective design, and testing for respiratory viruses on symptomatic patients only, rather than all ICU patients, the researchers noted. Other limitations include the inability to show a causal link between viral infections and patient outcomes and the heterogenous management of patients among different centers.

However, the results were strengthened by the large sample size and multivariate analysis, and support the need for interventions to prevent and treat severe RSV, they concluded.

The study received no outside funding. Lead author Dr. Coussement disclosed serving on advisory board for Sanofi.

Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.

Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.

“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.

In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).

Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).

Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.

Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.

These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.

A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.

However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.

The study was funded by Novartis. The researchers had no financial conflicts to disclose.

Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.

Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.

“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.

In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).

Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).

Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.

Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.

These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.

A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.

However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.

The study was funded by Novartis. The researchers had no financial conflicts to disclose.

Patients with severe asthma who were new to omalizumab showed significant clinical improvement after 2 weeks of treatment, according to data from a pilot study of 26 adults.

Although omalizumab is approved for severe allergic asthma, not all patients respond well, and are considered nonresponders in the absence of clinical benefits within 16 weeks of starting treatment, wrote Todor A. Popov, MD, of the University Hospital St. Ivan Rilski, Sofia, Bulgaria, and colleagues.

“Since airway inflammation is a cardinal feature of asthma, we reasoned that early changes in its level may determine the subsequent course of the disease,” they said.

In a study published in Annals of Allergy, Asthma & Immunology, the researchers recruited 26 adults with severe asthma who were new to biologic therapy and eligible for omalizumab. The patients ranged in age from 22 to 70 years, and 13 were men. Patients received omalizumab doses between 150 mg and 375 mg every 2-4 weeks based on body weight and pretreatment serum IgE levels, and they were assessed at baseline and followed for a total of 18 weeks (2-week run-in and 16 weeks of treatment).

Patients rated their overall discomfort from asthma on a 100-mm visual analogue scale (VAS). Asthma control was assessed via the asthma control questionnaire (ACQ), and disease-related quality of life was assessed via the Asthma Quality of Life Questionnaires (AQLQ). All patients reported significant improvement across all three measures after 2 weeks and through the study period after the first administration of omalizumab at week 0 (P < .001).

Clinical response was based on quantitative indicators of airway and systemic eosinophilic inflammation: fractional exhaled nitric oxide (FeNO), eosinophil cationic peptide (ECP), and the temperature of the exhaled air (EBT, exhaled breath temperature). The researchers also measured fractional EBT (FrEBT) by measuring the EBT of central and peripheral airways at the beginning and end of the expiration.

Overall, EBT decreased significantly after 2 weeks, and the decrease lasted until week 16. FrEBT decreased significantly after 4 weeks. ECP reached statistical significance at week 16 (P = .029). FeNO showed a downward trend, but the decrease did not reach statistical significance, the researchers wrote.

These results might suggest that “after blocking IgE, the eosinophilic inflammation is not suppressed well and fast enough,” the researchers noted. “Consequently, indicators of eosinophilic inflammation may not be suited for early predictors of success of omalizumab treatment,” they added. The drop in EBT after the first dose of omalizumab may predict effectiveness for a particular patient, while the FrEBT results “may mean that it takes longer to suppress the inflammatory process in the vast basin of the small airways,” they noted.

A key limitation of the findings was the small sample size, although the study was designed as a proof-of-concept on which to base sample size calculation for larger trials with EBT as a predictive marker, the researchers said.

However, the EBT and FrEBT signals reached statistical significance, and the results warrant confirmation in larger trials; such confirmation may spare patients from expensive and ineffective treatments, they concluded.

The study was funded by Novartis. The researchers had no financial conflicts to disclose.

Men with hypersexual disorder showed higher levels of oxytocin in their blood than did healthy control men without the disorder, in a study with 102 participants.

Hypersexual disorder (HD) is characterized by “excessive and persistent sexual behaviors in relation to various mood states, with an impulsivity component and experienced loss of control,” John Flanagan, MD, of the Karolinska Institutet in Stockholm and colleagues wrote. Although HD is not included as a separate diagnosis in the current DSM, the similar disorder of compulsive sexual behavior is included in the ICD.

Data on the pathophysiology of HD are limited, although a previous study by corresponding author Andreas Chatzittofis, MD, and colleagues showed evidence of neuroendocrine dysregulation in men with HD, and prompted the current study to explore the possible involvement of the oxytocinergic system in HD.

In the current study, published in the Journal of Clinical Endocrinology & Metabolism, the researchers identified 64 men with HD and 38 healthy male controls. The patients were help-seeking men older than 18 years diagnosed with HD who presented to a single center in Sweden during 2013-2014. The men were included in a randomized clinical trial of cognitive-behavioral therapy for HD, and 30 of them participated in a 7-week CBT program.

Oxytocin, secreted by the pituitary gland, is known to play a role in sexual behavior, but has not been examined in HD men, the researchers said. At baseline, the mean plasma oxytocin was 31.0 pM in the HD patients, which was significantly higher than the mean 16.9 pM in healthy controls (P < .001). However, the 30 HD men who underwent CBT showed significant improvement in oxytocin levels, from a mean pretreatment level of 30.5 to a mean posttreatment level of 20.2 pM (P = .0000019).

The study findings were limited by several factors, including the lack of data on oxytocin for a wait list or control group, as well as the inability to control for confounding factors such as diet, physical activity, ethnicity, and stress, and a lack of data on sexual activity prior to oxytocin measurements, the researchers noted.

However, “although there is no clear consensus at this point, previous studies support the use of oxytocin plasma levels as a surrogate variable for [cerebrospinal fluid] oxytocin activity,” the researchers wrote in their discussion. The current study findings support the potential of oxytocin as a biomarker for HD diagnostics and also as a measure of disease severity. Larger studies to confirm the findings, especially those that exclude potential confounders, would be valuable.

Oxytocin may be treatment target

The study is important because of the lack of knowledge regarding the pathophysiology underlying hypersexual disorder, Dr. Chatzittofis of the University of Cyprus, Nicosia, said in an interview. “This is the first study to indicate a role for oxytocin’s involvement” in hypersexual disorder in men. Dr. Chatzittofis led a team in a previous study that showed an association between HD in men and dysregulation of the hypothalamic pituitary adrenal axis.

In the current study, “we discovered that men with compulsive sexual behavior disorder had higher oxytocin levels, compared with healthy men,” said Dr. Chatzittofis, adding that the take-home message for clinicians is the potential of CBT for treatment. “Cognitive-behavior therapy led to a reduction in both hypersexual behavior and oxytocin levels.” The results suggest that oxytocin plays an important role in sex addiction.

Consequently, oxytocin may be a potential drug target for future pharmacologic treatment of hypersexual disorder, he added.

The study was supported by the Swedish Research Council, the Stockholm County Council, and by a partnership between Umeå University and Västerbotten County Council. The researchers had no financial conflicts to disclose.

Men with hypersexual disorder showed higher levels of oxytocin in their blood than did healthy control men without the disorder, in a study with 102 participants.

Hypersexual disorder (HD) is characterized by “excessive and persistent sexual behaviors in relation to various mood states, with an impulsivity component and experienced loss of control,” John Flanagan, MD, of the Karolinska Institutet in Stockholm and colleagues wrote. Although HD is not included as a separate diagnosis in the current DSM, the similar disorder of compulsive sexual behavior is included in the ICD.

Data on the pathophysiology of HD are limited, although a previous study by corresponding author Andreas Chatzittofis, MD, and colleagues showed evidence of neuroendocrine dysregulation in men with HD, and prompted the current study to explore the possible involvement of the oxytocinergic system in HD.

In the current study, published in the Journal of Clinical Endocrinology & Metabolism, the researchers identified 64 men with HD and 38 healthy male controls. The patients were help-seeking men older than 18 years diagnosed with HD who presented to a single center in Sweden during 2013-2014. The men were included in a randomized clinical trial of cognitive-behavioral therapy for HD, and 30 of them participated in a 7-week CBT program.

Oxytocin, secreted by the pituitary gland, is known to play a role in sexual behavior, but has not been examined in HD men, the researchers said. At baseline, the mean plasma oxytocin was 31.0 pM in the HD patients, which was significantly higher than the mean 16.9 pM in healthy controls (P < .001). However, the 30 HD men who underwent CBT showed significant improvement in oxytocin levels, from a mean pretreatment level of 30.5 to a mean posttreatment level of 20.2 pM (P = .0000019).

The study findings were limited by several factors, including the lack of data on oxytocin for a wait list or control group, as well as the inability to control for confounding factors such as diet, physical activity, ethnicity, and stress, and a lack of data on sexual activity prior to oxytocin measurements, the researchers noted.

However, “although there is no clear consensus at this point, previous studies support the use of oxytocin plasma levels as a surrogate variable for [cerebrospinal fluid] oxytocin activity,” the researchers wrote in their discussion. The current study findings support the potential of oxytocin as a biomarker for HD diagnostics and also as a measure of disease severity. Larger studies to confirm the findings, especially those that exclude potential confounders, would be valuable.

Oxytocin may be treatment target

The study is important because of the lack of knowledge regarding the pathophysiology underlying hypersexual disorder, Dr. Chatzittofis of the University of Cyprus, Nicosia, said in an interview. “This is the first study to indicate a role for oxytocin’s involvement” in hypersexual disorder in men. Dr. Chatzittofis led a team in a previous study that showed an association between HD in men and dysregulation of the hypothalamic pituitary adrenal axis.

In the current study, “we discovered that men with compulsive sexual behavior disorder had higher oxytocin levels, compared with healthy men,” said Dr. Chatzittofis, adding that the take-home message for clinicians is the potential of CBT for treatment. “Cognitive-behavior therapy led to a reduction in both hypersexual behavior and oxytocin levels.” The results suggest that oxytocin plays an important role in sex addiction.

Consequently, oxytocin may be a potential drug target for future pharmacologic treatment of hypersexual disorder, he added.

The study was supported by the Swedish Research Council, the Stockholm County Council, and by a partnership between Umeå University and Västerbotten County Council. The researchers had no financial conflicts to disclose.

Men with hypersexual disorder showed higher levels of oxytocin in their blood than did healthy control men without the disorder, in a study with 102 participants.

Hypersexual disorder (HD) is characterized by “excessive and persistent sexual behaviors in relation to various mood states, with an impulsivity component and experienced loss of control,” John Flanagan, MD, of the Karolinska Institutet in Stockholm and colleagues wrote. Although HD is not included as a separate diagnosis in the current DSM, the similar disorder of compulsive sexual behavior is included in the ICD.

Data on the pathophysiology of HD are limited, although a previous study by corresponding author Andreas Chatzittofis, MD, and colleagues showed evidence of neuroendocrine dysregulation in men with HD, and prompted the current study to explore the possible involvement of the oxytocinergic system in HD.

In the current study, published in the Journal of Clinical Endocrinology & Metabolism, the researchers identified 64 men with HD and 38 healthy male controls. The patients were help-seeking men older than 18 years diagnosed with HD who presented to a single center in Sweden during 2013-2014. The men were included in a randomized clinical trial of cognitive-behavioral therapy for HD, and 30 of them participated in a 7-week CBT program.

Oxytocin, secreted by the pituitary gland, is known to play a role in sexual behavior, but has not been examined in HD men, the researchers said. At baseline, the mean plasma oxytocin was 31.0 pM in the HD patients, which was significantly higher than the mean 16.9 pM in healthy controls (P < .001). However, the 30 HD men who underwent CBT showed significant improvement in oxytocin levels, from a mean pretreatment level of 30.5 to a mean posttreatment level of 20.2 pM (P = .0000019).

The study findings were limited by several factors, including the lack of data on oxytocin for a wait list or control group, as well as the inability to control for confounding factors such as diet, physical activity, ethnicity, and stress, and a lack of data on sexual activity prior to oxytocin measurements, the researchers noted.

However, “although there is no clear consensus at this point, previous studies support the use of oxytocin plasma levels as a surrogate variable for [cerebrospinal fluid] oxytocin activity,” the researchers wrote in their discussion. The current study findings support the potential of oxytocin as a biomarker for HD diagnostics and also as a measure of disease severity. Larger studies to confirm the findings, especially those that exclude potential confounders, would be valuable.

Oxytocin may be treatment target

The study is important because of the lack of knowledge regarding the pathophysiology underlying hypersexual disorder, Dr. Chatzittofis of the University of Cyprus, Nicosia, said in an interview. “This is the first study to indicate a role for oxytocin’s involvement” in hypersexual disorder in men. Dr. Chatzittofis led a team in a previous study that showed an association between HD in men and dysregulation of the hypothalamic pituitary adrenal axis.

In the current study, “we discovered that men with compulsive sexual behavior disorder had higher oxytocin levels, compared with healthy men,” said Dr. Chatzittofis, adding that the take-home message for clinicians is the potential of CBT for treatment. “Cognitive-behavior therapy led to a reduction in both hypersexual behavior and oxytocin levels.” The results suggest that oxytocin plays an important role in sex addiction.

Consequently, oxytocin may be a potential drug target for future pharmacologic treatment of hypersexual disorder, he added.

The study was supported by the Swedish Research Council, the Stockholm County Council, and by a partnership between Umeå University and Västerbotten County Council. The researchers had no financial conflicts to disclose.

The COVID-19 pandemic is now associated with the highest number of excess deaths worldwide since the 1918 flu pandemic, sometimes known as the “Spanish flu.”

Excess mortality is a way of quantifying the impact of a pandemic, based on overall mortality from nonpandemic periods. Mortality data over long periods of time are not available for many countries, but Switzerland, Sweden, and Spain have accumulated death count data for an uninterrupted period of more than 100 years.

In a study published in the Annals of Internal Medicine, Kaspar Staub, PhD, of the University of Zurich led a team of researchers in reviewing data on monthly excess deaths from all causes for Switzerland, Sweden, and Spain for 2020 to 2021. Dr. Staub and colleagues also compared these numbers to other pandemic and nonpandemic periods since the end of the 19th century. The starting years were 1877 for Switzerland, 1851 for Sweden, and 1908 for Spain.

The researchers collected data for monthly all-cause deaths from the statistical offices of each country and determined excess mortality by comparing these numbers to population size and age structure.

They found that 2020 showed the highest number of excess deaths since 1918, with relative excess of deaths of 12.5% in Switzerland, 8.5% in Sweden, and 17.3 % in Spain.

To put it another way, the number of excess deaths per 100,000 people was 100 for Switzerland, 75 for Sweden, and 155 for Spain.

“Our findings suggest that the pandemic led to the second-largest mortality disaster driven by a viral infection in more than 100 years in the three countries we studied, second only to the 1918 influenza pandemic,” the researchers wrote.

They explained that the excess mortality for the year 1918 was six to seven times higher than the 2020 numbers, but that the 2020 numbers might have been higher without the strong public health interventions taken worldwide to mitigate the impact of the COVID-19 pandemic.

“Early estimates suggest that vaccination prevented approximately 470,000 deaths in persons aged 60 years or older across 33 European countries between December 2019 and November 2021,” they wrote. However, because the COVID-19 pandemic is ongoing, “a more conclusive assessment will have to wait,” they added.

The 2020 numbers also were higher than most mortality rates since 1918, including peak years of previous influenza pandemics that occurred in 1957, 1968, 1977, and, most recently, the swine flu pandemic of 2009 which was caused by a novel strain of the H1N1 influenza virus.

The study findings had some limitations. For example, only three countries were included. Also, monthly death numbers according to sex, age, and cause of death were available only for the past 60 years, and data from years before the 20th century may not be reliable, the researchers said.

The new study does not account for the long-term effects of patients suffering from long COVID, they noted.

Study findings support strong public health response

“With the COVID-19 pandemic ongoing, this study reinforces the historic magnitude of the problem in terms of mortality and could add to the justification for ongoing public health measures such as vaccination drives and vaccine mandates to curb deaths,” said Suman Pal, MD, an internal medicine physician at the University of New Mexico, Albuquerque, in an interview.

“The results are surprising because when we view the rapid advancement in medical science over the last few decades, which have led to a decline in mortality from many previously fatal diseases, the scale of excess mortality from COVID-19 seems to have offset many such gains in the past 2 years.”

Prior studies of United States mortality data have estimated that excess deaths in the United States in 2020 exceeded the deaths attributed to COVID-19, said Dr. Pal. “The findings of this study could help clinicians in their discussion of the need for COVID-19 prevention measures with their patients” and inform discussions between doctors and patients about prevention strategies, he explained.

“Emphasizing that this pandemic is the second-largest cause of death due to a viral infection in a century could help patients understand the need for public health measures that may be viewed as unprecedented, such as government-imposed lockdowns, contact tracing, mask requirements, restrictions on travel, and vaccine mandates,” Dr. Pal noted. Better understanding of the evidence behind such measures may decrease the public’s resistance to following them, he added.As for additional research, “region-specific analysis of excess deaths may help estimate the impact of COVID-19 better, especially in regions where data reporting may be unreliable.”

Dr. F. Perry Wilson's take on study

“All-cause mortality is a key metric to assess the impact of the pandemic, because each death is treated equally,” said F. Perry Wilson, MD, of Yale University, in an interview. “With this type of analysis, there is no vague definition of a death from COVID or with COVID,” he explained. “A death is a death, and more deaths than expected is, of course, a bad thing. These analyses give a high-level view of the true human cost of the pandemic,” he said.

Yale School of Medicine

Dr. Wilson said he was not surprised by the findings. “There have been multiple studies, across multiple countries including the United States, which show similar findings—that observed deaths during this pandemic are substantially higher than expected,” he said. The current study findings are unique in that they compare the current pandemic to death rates in a nearly unbroken chain into the last century using data that only a few countries can provide, he noted. 

The mortality data are “quite similar to what we see in the United States, with the exception that Spain was particularly hard-hit in the first COVID-19 wave in April 2020, said Dr. Wilson. By contrast, “the U.S. had substantially more excess deaths in the recent Delta wave, presumably due to lower vaccination uptake,” he added.

The current study is important for clinicians and their patients, said Dr. Wilson. “Data like these can help cut through some of the misinformation, such as the idea that only people who would have died anyway die of COVID, or that COVID is not severe,” he emphasized. “Overall death data are quite clear that far more people, millions more people, died over the last 22 months than could possibly be explained except by a global-level mortality event,” he said. 

“One thing this study reminds us of is the value of high-quality data,” said Dr. Wilson. “Few countries have near complete vital statistics records on their entire populations and these can be so crucial to understand the true impact of pandemics and other disasters,” he explained. Of course, mortality data also serve as a reminder “that COVID is a serious disease: a once-in-a-century (we hope) pandemic,” he added.

The current study showed that excess death rates were similar, but not the same, from country to country, Dr. Wilson noted. “Moving forward, we need to learn what factors, from vaccination to social distancing strategies,” saved lives around the world,” he said. 

The study was supported by the Foundation for Research in Science and the Humanities at the University of Zurich, the Swiss National Science Foundation, and the U.S. National Institute of Allergy and Infectious Diseases. The researchers, Dr. Pal, and Dr. Wilson had no financial conflicts.

*This article was updated on 2/1/2022.

The COVID-19 pandemic is now associated with the highest number of excess deaths worldwide since the 1918 flu pandemic, sometimes known as the “Spanish flu.”

Excess mortality is a way of quantifying the impact of a pandemic, based on overall mortality from nonpandemic periods. Mortality data over long periods of time are not available for many countries, but Switzerland, Sweden, and Spain have accumulated death count data for an uninterrupted period of more than 100 years.

In a study published in the Annals of Internal Medicine, Kaspar Staub, PhD, of the University of Zurich led a team of researchers in reviewing data on monthly excess deaths from all causes for Switzerland, Sweden, and Spain for 2020 to 2021. Dr. Staub and colleagues also compared these numbers to other pandemic and nonpandemic periods since the end of the 19th century. The starting years were 1877 for Switzerland, 1851 for Sweden, and 1908 for Spain.

The researchers collected data for monthly all-cause deaths from the statistical offices of each country and determined excess mortality by comparing these numbers to population size and age structure.

They found that 2020 showed the highest number of excess deaths since 1918, with relative excess of deaths of 12.5% in Switzerland, 8.5% in Sweden, and 17.3 % in Spain.

To put it another way, the number of excess deaths per 100,000 people was 100 for Switzerland, 75 for Sweden, and 155 for Spain.

“Our findings suggest that the pandemic led to the second-largest mortality disaster driven by a viral infection in more than 100 years in the three countries we studied, second only to the 1918 influenza pandemic,” the researchers wrote.

They explained that the excess mortality for the year 1918 was six to seven times higher than the 2020 numbers, but that the 2020 numbers might have been higher without the strong public health interventions taken worldwide to mitigate the impact of the COVID-19 pandemic.

“Early estimates suggest that vaccination prevented approximately 470,000 deaths in persons aged 60 years or older across 33 European countries between December 2019 and November 2021,” they wrote. However, because the COVID-19 pandemic is ongoing, “a more conclusive assessment will have to wait,” they added.

The 2020 numbers also were higher than most mortality rates since 1918, including peak years of previous influenza pandemics that occurred in 1957, 1968, 1977, and, most recently, the swine flu pandemic of 2009 which was caused by a novel strain of the H1N1 influenza virus.

The study findings had some limitations. For example, only three countries were included. Also, monthly death numbers according to sex, age, and cause of death were available only for the past 60 years, and data from years before the 20th century may not be reliable, the researchers said.

The new study does not account for the long-term effects of patients suffering from long COVID, they noted.

Study findings support strong public health response

“With the COVID-19 pandemic ongoing, this study reinforces the historic magnitude of the problem in terms of mortality and could add to the justification for ongoing public health measures such as vaccination drives and vaccine mandates to curb deaths,” said Suman Pal, MD, an internal medicine physician at the University of New Mexico, Albuquerque, in an interview.

“The results are surprising because when we view the rapid advancement in medical science over the last few decades, which have led to a decline in mortality from many previously fatal diseases, the scale of excess mortality from COVID-19 seems to have offset many such gains in the past 2 years.”

Prior studies of United States mortality data have estimated that excess deaths in the United States in 2020 exceeded the deaths attributed to COVID-19, said Dr. Pal. “The findings of this study could help clinicians in their discussion of the need for COVID-19 prevention measures with their patients” and inform discussions between doctors and patients about prevention strategies, he explained.

“Emphasizing that this pandemic is the second-largest cause of death due to a viral infection in a century could help patients understand the need for public health measures that may be viewed as unprecedented, such as government-imposed lockdowns, contact tracing, mask requirements, restrictions on travel, and vaccine mandates,” Dr. Pal noted. Better understanding of the evidence behind such measures may decrease the public’s resistance to following them, he added.As for additional research, “region-specific analysis of excess deaths may help estimate the impact of COVID-19 better, especially in regions where data reporting may be unreliable.”

Dr. F. Perry Wilson's take on study

“All-cause mortality is a key metric to assess the impact of the pandemic, because each death is treated equally,” said F. Perry Wilson, MD, of Yale University, in an interview. “With this type of analysis, there is no vague definition of a death from COVID or with COVID,” he explained. “A death is a death, and more deaths than expected is, of course, a bad thing. These analyses give a high-level view of the true human cost of the pandemic,” he said.

Yale School of Medicine

Dr. Wilson said he was not surprised by the findings. “There have been multiple studies, across multiple countries including the United States, which show similar findings—that observed deaths during this pandemic are substantially higher than expected,” he said. The current study findings are unique in that they compare the current pandemic to death rates in a nearly unbroken chain into the last century using data that only a few countries can provide, he noted. 

The mortality data are “quite similar to what we see in the United States, with the exception that Spain was particularly hard-hit in the first COVID-19 wave in April 2020, said Dr. Wilson. By contrast, “the U.S. had substantially more excess deaths in the recent Delta wave, presumably due to lower vaccination uptake,” he added.

The current study is important for clinicians and their patients, said Dr. Wilson. “Data like these can help cut through some of the misinformation, such as the idea that only people who would have died anyway die of COVID, or that COVID is not severe,” he emphasized. “Overall death data are quite clear that far more people, millions more people, died over the last 22 months than could possibly be explained except by a global-level mortality event,” he said. 

“One thing this study reminds us of is the value of high-quality data,” said Dr. Wilson. “Few countries have near complete vital statistics records on their entire populations and these can be so crucial to understand the true impact of pandemics and other disasters,” he explained. Of course, mortality data also serve as a reminder “that COVID is a serious disease: a once-in-a-century (we hope) pandemic,” he added.

The current study showed that excess death rates were similar, but not the same, from country to country, Dr. Wilson noted. “Moving forward, we need to learn what factors, from vaccination to social distancing strategies,” saved lives around the world,” he said. 

The study was supported by the Foundation for Research in Science and the Humanities at the University of Zurich, the Swiss National Science Foundation, and the U.S. National Institute of Allergy and Infectious Diseases. The researchers, Dr. Pal, and Dr. Wilson had no financial conflicts.

*This article was updated on 2/1/2022.

The COVID-19 pandemic is now associated with the highest number of excess deaths worldwide since the 1918 flu pandemic, sometimes known as the “Spanish flu.”

Excess mortality is a way of quantifying the impact of a pandemic, based on overall mortality from nonpandemic periods. Mortality data over long periods of time are not available for many countries, but Switzerland, Sweden, and Spain have accumulated death count data for an uninterrupted period of more than 100 years.

In a study published in the Annals of Internal Medicine, Kaspar Staub, PhD, of the University of Zurich led a team of researchers in reviewing data on monthly excess deaths from all causes for Switzerland, Sweden, and Spain for 2020 to 2021. Dr. Staub and colleagues also compared these numbers to other pandemic and nonpandemic periods since the end of the 19th century. The starting years were 1877 for Switzerland, 1851 for Sweden, and 1908 for Spain.

The researchers collected data for monthly all-cause deaths from the statistical offices of each country and determined excess mortality by comparing these numbers to population size and age structure.

They found that 2020 showed the highest number of excess deaths since 1918, with relative excess of deaths of 12.5% in Switzerland, 8.5% in Sweden, and 17.3 % in Spain.

To put it another way, the number of excess deaths per 100,000 people was 100 for Switzerland, 75 for Sweden, and 155 for Spain.

“Our findings suggest that the pandemic led to the second-largest mortality disaster driven by a viral infection in more than 100 years in the three countries we studied, second only to the 1918 influenza pandemic,” the researchers wrote.

They explained that the excess mortality for the year 1918 was six to seven times higher than the 2020 numbers, but that the 2020 numbers might have been higher without the strong public health interventions taken worldwide to mitigate the impact of the COVID-19 pandemic.

“Early estimates suggest that vaccination prevented approximately 470,000 deaths in persons aged 60 years or older across 33 European countries between December 2019 and November 2021,” they wrote. However, because the COVID-19 pandemic is ongoing, “a more conclusive assessment will have to wait,” they added.

The 2020 numbers also were higher than most mortality rates since 1918, including peak years of previous influenza pandemics that occurred in 1957, 1968, 1977, and, most recently, the swine flu pandemic of 2009 which was caused by a novel strain of the H1N1 influenza virus.

The study findings had some limitations. For example, only three countries were included. Also, monthly death numbers according to sex, age, and cause of death were available only for the past 60 years, and data from years before the 20th century may not be reliable, the researchers said.

The new study does not account for the long-term effects of patients suffering from long COVID, they noted.

Study findings support strong public health response

“With the COVID-19 pandemic ongoing, this study reinforces the historic magnitude of the problem in terms of mortality and could add to the justification for ongoing public health measures such as vaccination drives and vaccine mandates to curb deaths,” said Suman Pal, MD, an internal medicine physician at the University of New Mexico, Albuquerque, in an interview.

“The results are surprising because when we view the rapid advancement in medical science over the last few decades, which have led to a decline in mortality from many previously fatal diseases, the scale of excess mortality from COVID-19 seems to have offset many such gains in the past 2 years.”

Prior studies of United States mortality data have estimated that excess deaths in the United States in 2020 exceeded the deaths attributed to COVID-19, said Dr. Pal. “The findings of this study could help clinicians in their discussion of the need for COVID-19 prevention measures with their patients” and inform discussions between doctors and patients about prevention strategies, he explained.

“Emphasizing that this pandemic is the second-largest cause of death due to a viral infection in a century could help patients understand the need for public health measures that may be viewed as unprecedented, such as government-imposed lockdowns, contact tracing, mask requirements, restrictions on travel, and vaccine mandates,” Dr. Pal noted. Better understanding of the evidence behind such measures may decrease the public’s resistance to following them, he added.As for additional research, “region-specific analysis of excess deaths may help estimate the impact of COVID-19 better, especially in regions where data reporting may be unreliable.”

Dr. F. Perry Wilson's take on study

“All-cause mortality is a key metric to assess the impact of the pandemic, because each death is treated equally,” said F. Perry Wilson, MD, of Yale University, in an interview. “With this type of analysis, there is no vague definition of a death from COVID or with COVID,” he explained. “A death is a death, and more deaths than expected is, of course, a bad thing. These analyses give a high-level view of the true human cost of the pandemic,” he said.

Yale School of Medicine

Dr. Wilson said he was not surprised by the findings. “There have been multiple studies, across multiple countries including the United States, which show similar findings—that observed deaths during this pandemic are substantially higher than expected,” he said. The current study findings are unique in that they compare the current pandemic to death rates in a nearly unbroken chain into the last century using data that only a few countries can provide, he noted. 

The mortality data are “quite similar to what we see in the United States, with the exception that Spain was particularly hard-hit in the first COVID-19 wave in April 2020, said Dr. Wilson. By contrast, “the U.S. had substantially more excess deaths in the recent Delta wave, presumably due to lower vaccination uptake,” he added.

The current study is important for clinicians and their patients, said Dr. Wilson. “Data like these can help cut through some of the misinformation, such as the idea that only people who would have died anyway die of COVID, or that COVID is not severe,” he emphasized. “Overall death data are quite clear that far more people, millions more people, died over the last 22 months than could possibly be explained except by a global-level mortality event,” he said. 

“One thing this study reminds us of is the value of high-quality data,” said Dr. Wilson. “Few countries have near complete vital statistics records on their entire populations and these can be so crucial to understand the true impact of pandemics and other disasters,” he explained. Of course, mortality data also serve as a reminder “that COVID is a serious disease: a once-in-a-century (we hope) pandemic,” he added.

The current study showed that excess death rates were similar, but not the same, from country to country, Dr. Wilson noted. “Moving forward, we need to learn what factors, from vaccination to social distancing strategies,” saved lives around the world,” he said. 

The study was supported by the Foundation for Research in Science and the Humanities at the University of Zurich, the Swiss National Science Foundation, and the U.S. National Institute of Allergy and Infectious Diseases. The researchers, Dr. Pal, and Dr. Wilson had no financial conflicts.

*This article was updated on 2/1/2022.

Women who used marijuana during pregnancy were at increased risk for adverse neonatal outcomes, based on data from a meta-analysis of nearly 60,000 individuals.

Marijuana misuse remains a top substance use disorder and studies of prenatal use show a prevalence as high as 22% worldwide, wrote Greg J. Marchand, MD, of the Marchand Institute for Minimally Invasive Surgery, Mesa, Ariz., and colleagues.

“The prevalence of marijuana use during pregnancy may continue to increase, given that there is a suggested association between legalized recreational marijuana and increased use in prenatal and postpartum periods,” they wrote. “Remarkably, 34%-60% of individuals who use marijuana keep using it during pregnancy,” and many women cite a belief that marijuana is safe to use while pregnant, they noted.

Cannabinoid receptors are present in the developing fetus by the start of the second trimester, and exposure to exogenous cannabinoids may be associated with changes in the prefrontal cortex, including development and function, the researchers said. However, previous studies of an association between maternal marijuana use and poor neonatal outcomes have been inconsistent, they added.

In a study published in JAMA Network Open, the researchers identified 16 interventional and observational studies including 59,138 patients; each study included pregnant women who were exposed to marijuana, compared with those not exposed to marijuana, along with neonatal outcomes. The data selection included studies published until Aug. 16, 2021, and 10 studies were published in 2015 or later.

Overall, the risk for seven adverse neonatal outcomes was significantly increased among women who were exposed to marijuana during pregnancy, compared with those not exposed. The researchers identified increased risk for birth weight less than 2,500 g (relative risk, 2.06; P = .005), small for gestational age (RR, 1.61; P < .001), preterm delivery (RR, 1.28; P < .001), and NICU admission (RR, 1.38; P < .001). In addition, they found significant differences in mean birth weight (mean difference, −112.30 g; P < .001), Apgar score at 1 minute (mean difference, −0.26; P = .002), and infant head circumference (mean difference, −0.34cm; P = .02) between women who used marijuana during pregnancy and those who did not.

The study findings were limited by several factors, including the assessment of only cohort studies, which might suffer from bias given their retrospective designs, the researchers noted. Other limitations included the reliance on self-reports, the inability to adjust for tobacco/marijuana coexposure, and the lack of differentiation between levels of use and between different types of marijuana ingestion, they added.

However, the results support an association between marijuana use and adverse neonatal outcomes, and the researchers recommended additional studies of both maternal and neonatal outcomes associated with marijuana exposure. “Given increasing marijuana legalization and use worldwide, raising awareness and educating patients about these adverse outcomes may help to improve neonatal health,” they concluded.

New research prompted new review

The motivation to conduct this analysis at this time was prompted by the publication of several new, high-quality studies on the use of marijuana in pregnancy, according to Dr. Marchand. “It’s been a few years since a full analysis of all of the available data had been done, so we decided it was time to see if the old conclusions still held,” he said in an interview.

Dr. Marchand said he was surprised to see such a clear connection to preterm deliveries and lower birth weights. “When we perform a meta-analysis, we use all of the available data, and some important studies performed as recently as the past few years provided the depth of evidence behind these connections,” he said. “We didn’t have that level of evidence the last time this topic was studied only a few years ago,” he added.

The study is the largest meta-analysis on this topic to date, so the message to clinicians is highly significant, Dr. Marchand said. That message is “that we now have a very high level of evidence to say that smoking marijuana during pregnancy is harmful, and we (physicians especially) can no longer state that we just don’t know,” he said. “This is going to mean that deciding to smoke marijuana during your pregnancy is also deciding to do something that can harm your baby,” he emphasized. “This paper also will force some difficult decisions for mothers who use marijuana to treat medical problems, and there may not be good substitute treatments for some of these conditions, especially chronic pain and anxiety,” Dr. Marchand noted. “This will set up a difficult risk-versus-benefits situation, where these mothers, ideally with the help of their physicians, will have to decide if the risks of stopping marijuana outweigh the possible harm to the unborn baby,” he said.

As for additional research, long-term studies to assess behavioral changes as exposed children grow up would be beneficial, Dr. Marchand said. Such studies “could really help us balance the risk of marijuana exposure in pregnancy, especially if it is being used to treat serious medical conditions,” he noted.

Findings are a call to action

The view among many women that prenatal cannabis use is safe and without consequence “is a false narrative perpetuated by a combination of outdated evidence and recent changes to state-level cannabis policies,” wrote Kara R. Skelton, PhD, of Towson (Md.) University, and Sara E. Benjamin-Neelon, PhD, of Johns Hopkins University, Baltimore, in an accompanying editorial.

The findings from the current study add to the growing evidence that prenatal cannabis use is associated with adverse birth outcomes, they wrote. “Clinician-directed communication about cannabis has been criticized by pregnant women, with recent findings supporting a need for increased cannabis communication by clinicians,” and not only clinicians, but all health professionals who encounter women who are pregnant or attempting pregnancy should not miss the opportunity to communicate the risks of prenatal cannabis use, they emphasized.

The authors highlighted some of the current study’s limitations, including the inability to determine a dose-response association, the reliance on self-reports, and the lack of adjustment for tobacco/marijuana coexposure. However, they noted that the inclusion of recent studies (10 published in 2015 or later) strengthens the results because of the significant increase in the potency of Δ-9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, in recent decades.

“We urge clinicians, public health professionals, and policy makers to carefully consider the consequences of in utero cannabis exposure identified by Marchand et al. and partner to ensure prioritization of infant and child health during this time of precipitous cannabis legalization and commercialization,” the authors emphasized. “Without necessary safeguards to protect neonatal health, prenatal cannabis use poses a substantial threat to current and future generations of children,” they wrote.

The study received no outside funding. The researchers had no financial conflicts to disclose. The editorialists had no financial conflicts to disclose.

Women who used marijuana during pregnancy were at increased risk for adverse neonatal outcomes, based on data from a meta-analysis of nearly 60,000 individuals.

Marijuana misuse remains a top substance use disorder and studies of prenatal use show a prevalence as high as 22% worldwide, wrote Greg J. Marchand, MD, of the Marchand Institute for Minimally Invasive Surgery, Mesa, Ariz., and colleagues.

“The prevalence of marijuana use during pregnancy may continue to increase, given that there is a suggested association between legalized recreational marijuana and increased use in prenatal and postpartum periods,” they wrote. “Remarkably, 34%-60% of individuals who use marijuana keep using it during pregnancy,” and many women cite a belief that marijuana is safe to use while pregnant, they noted.

Cannabinoid receptors are present in the developing fetus by the start of the second trimester, and exposure to exogenous cannabinoids may be associated with changes in the prefrontal cortex, including development and function, the researchers said. However, previous studies of an association between maternal marijuana use and poor neonatal outcomes have been inconsistent, they added.

In a study published in JAMA Network Open, the researchers identified 16 interventional and observational studies including 59,138 patients; each study included pregnant women who were exposed to marijuana, compared with those not exposed to marijuana, along with neonatal outcomes. The data selection included studies published until Aug. 16, 2021, and 10 studies were published in 2015 or later.

Overall, the risk for seven adverse neonatal outcomes was significantly increased among women who were exposed to marijuana during pregnancy, compared with those not exposed. The researchers identified increased risk for birth weight less than 2,500 g (relative risk, 2.06; P = .005), small for gestational age (RR, 1.61; P < .001), preterm delivery (RR, 1.28; P < .001), and NICU admission (RR, 1.38; P < .001). In addition, they found significant differences in mean birth weight (mean difference, −112.30 g; P < .001), Apgar score at 1 minute (mean difference, −0.26; P = .002), and infant head circumference (mean difference, −0.34cm; P = .02) between women who used marijuana during pregnancy and those who did not.

The study findings were limited by several factors, including the assessment of only cohort studies, which might suffer from bias given their retrospective designs, the researchers noted. Other limitations included the reliance on self-reports, the inability to adjust for tobacco/marijuana coexposure, and the lack of differentiation between levels of use and between different types of marijuana ingestion, they added.

However, the results support an association between marijuana use and adverse neonatal outcomes, and the researchers recommended additional studies of both maternal and neonatal outcomes associated with marijuana exposure. “Given increasing marijuana legalization and use worldwide, raising awareness and educating patients about these adverse outcomes may help to improve neonatal health,” they concluded.

New research prompted new review

The motivation to conduct this analysis at this time was prompted by the publication of several new, high-quality studies on the use of marijuana in pregnancy, according to Dr. Marchand. “It’s been a few years since a full analysis of all of the available data had been done, so we decided it was time to see if the old conclusions still held,” he said in an interview.

Dr. Marchand said he was surprised to see such a clear connection to preterm deliveries and lower birth weights. “When we perform a meta-analysis, we use all of the available data, and some important studies performed as recently as the past few years provided the depth of evidence behind these connections,” he said. “We didn’t have that level of evidence the last time this topic was studied only a few years ago,” he added.

The study is the largest meta-analysis on this topic to date, so the message to clinicians is highly significant, Dr. Marchand said. That message is “that we now have a very high level of evidence to say that smoking marijuana during pregnancy is harmful, and we (physicians especially) can no longer state that we just don’t know,” he said. “This is going to mean that deciding to smoke marijuana during your pregnancy is also deciding to do something that can harm your baby,” he emphasized. “This paper also will force some difficult decisions for mothers who use marijuana to treat medical problems, and there may not be good substitute treatments for some of these conditions, especially chronic pain and anxiety,” Dr. Marchand noted. “This will set up a difficult risk-versus-benefits situation, where these mothers, ideally with the help of their physicians, will have to decide if the risks of stopping marijuana outweigh the possible harm to the unborn baby,” he said.

As for additional research, long-term studies to assess behavioral changes as exposed children grow up would be beneficial, Dr. Marchand said. Such studies “could really help us balance the risk of marijuana exposure in pregnancy, especially if it is being used to treat serious medical conditions,” he noted.

Findings are a call to action

The view among many women that prenatal cannabis use is safe and without consequence “is a false narrative perpetuated by a combination of outdated evidence and recent changes to state-level cannabis policies,” wrote Kara R. Skelton, PhD, of Towson (Md.) University, and Sara E. Benjamin-Neelon, PhD, of Johns Hopkins University, Baltimore, in an accompanying editorial.

The findings from the current study add to the growing evidence that prenatal cannabis use is associated with adverse birth outcomes, they wrote. “Clinician-directed communication about cannabis has been criticized by pregnant women, with recent findings supporting a need for increased cannabis communication by clinicians,” and not only clinicians, but all health professionals who encounter women who are pregnant or attempting pregnancy should not miss the opportunity to communicate the risks of prenatal cannabis use, they emphasized.

The authors highlighted some of the current study’s limitations, including the inability to determine a dose-response association, the reliance on self-reports, and the lack of adjustment for tobacco/marijuana coexposure. However, they noted that the inclusion of recent studies (10 published in 2015 or later) strengthens the results because of the significant increase in the potency of Δ-9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, in recent decades.

“We urge clinicians, public health professionals, and policy makers to carefully consider the consequences of in utero cannabis exposure identified by Marchand et al. and partner to ensure prioritization of infant and child health during this time of precipitous cannabis legalization and commercialization,” the authors emphasized. “Without necessary safeguards to protect neonatal health, prenatal cannabis use poses a substantial threat to current and future generations of children,” they wrote.

The study received no outside funding. The researchers had no financial conflicts to disclose. The editorialists had no financial conflicts to disclose.

Women who used marijuana during pregnancy were at increased risk for adverse neonatal outcomes, based on data from a meta-analysis of nearly 60,000 individuals.

Marijuana misuse remains a top substance use disorder and studies of prenatal use show a prevalence as high as 22% worldwide, wrote Greg J. Marchand, MD, of the Marchand Institute for Minimally Invasive Surgery, Mesa, Ariz., and colleagues.

“The prevalence of marijuana use during pregnancy may continue to increase, given that there is a suggested association between legalized recreational marijuana and increased use in prenatal and postpartum periods,” they wrote. “Remarkably, 34%-60% of individuals who use marijuana keep using it during pregnancy,” and many women cite a belief that marijuana is safe to use while pregnant, they noted.

Cannabinoid receptors are present in the developing fetus by the start of the second trimester, and exposure to exogenous cannabinoids may be associated with changes in the prefrontal cortex, including development and function, the researchers said. However, previous studies of an association between maternal marijuana use and poor neonatal outcomes have been inconsistent, they added.

In a study published in JAMA Network Open, the researchers identified 16 interventional and observational studies including 59,138 patients; each study included pregnant women who were exposed to marijuana, compared with those not exposed to marijuana, along with neonatal outcomes. The data selection included studies published until Aug. 16, 2021, and 10 studies were published in 2015 or later.

Overall, the risk for seven adverse neonatal outcomes was significantly increased among women who were exposed to marijuana during pregnancy, compared with those not exposed. The researchers identified increased risk for birth weight less than 2,500 g (relative risk, 2.06; P = .005), small for gestational age (RR, 1.61; P < .001), preterm delivery (RR, 1.28; P < .001), and NICU admission (RR, 1.38; P < .001). In addition, they found significant differences in mean birth weight (mean difference, −112.30 g; P < .001), Apgar score at 1 minute (mean difference, −0.26; P = .002), and infant head circumference (mean difference, −0.34cm; P = .02) between women who used marijuana during pregnancy and those who did not.

The study findings were limited by several factors, including the assessment of only cohort studies, which might suffer from bias given their retrospective designs, the researchers noted. Other limitations included the reliance on self-reports, the inability to adjust for tobacco/marijuana coexposure, and the lack of differentiation between levels of use and between different types of marijuana ingestion, they added.

However, the results support an association between marijuana use and adverse neonatal outcomes, and the researchers recommended additional studies of both maternal and neonatal outcomes associated with marijuana exposure. “Given increasing marijuana legalization and use worldwide, raising awareness and educating patients about these adverse outcomes may help to improve neonatal health,” they concluded.

New research prompted new review

The motivation to conduct this analysis at this time was prompted by the publication of several new, high-quality studies on the use of marijuana in pregnancy, according to Dr. Marchand. “It’s been a few years since a full analysis of all of the available data had been done, so we decided it was time to see if the old conclusions still held,” he said in an interview.

Dr. Marchand said he was surprised to see such a clear connection to preterm deliveries and lower birth weights. “When we perform a meta-analysis, we use all of the available data, and some important studies performed as recently as the past few years provided the depth of evidence behind these connections,” he said. “We didn’t have that level of evidence the last time this topic was studied only a few years ago,” he added.

The study is the largest meta-analysis on this topic to date, so the message to clinicians is highly significant, Dr. Marchand said. That message is “that we now have a very high level of evidence to say that smoking marijuana during pregnancy is harmful, and we (physicians especially) can no longer state that we just don’t know,” he said. “This is going to mean that deciding to smoke marijuana during your pregnancy is also deciding to do something that can harm your baby,” he emphasized. “This paper also will force some difficult decisions for mothers who use marijuana to treat medical problems, and there may not be good substitute treatments for some of these conditions, especially chronic pain and anxiety,” Dr. Marchand noted. “This will set up a difficult risk-versus-benefits situation, where these mothers, ideally with the help of their physicians, will have to decide if the risks of stopping marijuana outweigh the possible harm to the unborn baby,” he said.

As for additional research, long-term studies to assess behavioral changes as exposed children grow up would be beneficial, Dr. Marchand said. Such studies “could really help us balance the risk of marijuana exposure in pregnancy, especially if it is being used to treat serious medical conditions,” he noted.

Findings are a call to action

The view among many women that prenatal cannabis use is safe and without consequence “is a false narrative perpetuated by a combination of outdated evidence and recent changes to state-level cannabis policies,” wrote Kara R. Skelton, PhD, of Towson (Md.) University, and Sara E. Benjamin-Neelon, PhD, of Johns Hopkins University, Baltimore, in an accompanying editorial.

The findings from the current study add to the growing evidence that prenatal cannabis use is associated with adverse birth outcomes, they wrote. “Clinician-directed communication about cannabis has been criticized by pregnant women, with recent findings supporting a need for increased cannabis communication by clinicians,” and not only clinicians, but all health professionals who encounter women who are pregnant or attempting pregnancy should not miss the opportunity to communicate the risks of prenatal cannabis use, they emphasized.

The authors highlighted some of the current study’s limitations, including the inability to determine a dose-response association, the reliance on self-reports, and the lack of adjustment for tobacco/marijuana coexposure. However, they noted that the inclusion of recent studies (10 published in 2015 or later) strengthens the results because of the significant increase in the potency of Δ-9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, in recent decades.

“We urge clinicians, public health professionals, and policy makers to carefully consider the consequences of in utero cannabis exposure identified by Marchand et al. and partner to ensure prioritization of infant and child health during this time of precipitous cannabis legalization and commercialization,” the authors emphasized. “Without necessary safeguards to protect neonatal health, prenatal cannabis use poses a substantial threat to current and future generations of children,” they wrote.

The study received no outside funding. The researchers had no financial conflicts to disclose. The editorialists had no financial conflicts to disclose.

Achieving steroid-free clinical and endoscopic remission does not decrease the risk of Crohn’s disease progression measured by surgery, hospitalization, or initiation of new treatments, according to a post hoc analysis of data from a prospective RCT.

The therapeutic goals of Crohn’s disease have evolved from controlling symptoms to blocking disease progression and reducing complications, wrote David Laharie, MD, of Hôpital Haut-Lévêque, Pessac, France, and colleagues. The goal of steroid-free remission has been used as an endpoint of treatment, but data on the impact of such remission on long-term disease are limited, the researchers noted in a retrospective study published in Clinical Gastroenterology and Hepatology.

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In the study, the researchers reviewed data from 95 adults with early Crohn’s disease (CD) who participated in the TAILORIX trial involving treatment with infliximab and immunomodulators. The primary endpoint of the TAILORIX trial was sustained corticosteroid-free remission from week 22 to 54. In the current study, the primary endpoint was progression-free survival at 1, 3, and 5 years in patients who did or did not meet the TAILORIX primary endpoint. The median disease duration was 4.5 months, and the median follow-up was 64.2 months.

Progression-free survival was defined as a composite of luminal surgery, anal surgery, hospitalization, and the need for a new CD treatment during the follow-up period.

In the study population, 45 patients achieved corticosteroid-free remission and 50 did not. At 54 weeks, 17 patients with corticosteroid-free remission (38%) and 28 patients without remission (56%) achieved complete mucosal healing, and progression-free survival rates were similar between these groups.

Overall, the rates of progression-free survival at 1, 3, and 5 years were not significantly different between the remission and nonremission groups: 86% versus 91%, respectively, at 1 year; 70% for both groups at 3 years; and 64% and 61%, respectively, at 5 years.

The researchers also compared individual components of the primary endpoint (luminal surgery, anal surgery, hospitalization, and the need for a new CD treatment), and found no significant differences in survival rates in patients who had and had not achieved steroid-free remission.

Survival rates without luminal surgery at 1, 3, and 5 years were 97% versus 96%, 93% versus 90%, and 87% versus 82%, respectively, for remission and nonremission groups. Similarly, survival rates without anal surgery were 93%, 86%, and 86% versus 96%, 88%, and 85%, respectively, for the two groups. Rates of hospitalization-free survival at 1, 3, and 5 years were 90% versus 92%, 81% versus 81%, and 78% versus 69%, respectively, in the remission and nonremission groups. Survival rates without a new systemic CD treatment also were similar at 1, 3, and 5 years: 93% versus 95%, 71% versus 93%, and 60% versus 51%, respectively, for the remission and nonremission groups.

CD progression was not associated with not achieving corticosteroid-free remission (hazard ratio, 0.861). Other factors that were not associated with disease progression in this study included CRP greater than 5 mg/L, age older than 30 years, active smoking, and B1 phenotype.

The researchers noted that, although endoscopic and clinical remission is currently recommended for CD, “there is no validated or standardized definition of this endoscopic goal.” The high rates of survival without major abdominal surgery, regardless of remission status, suggest a significant impact of early combination therapy for CD patients who were biologic naive. Other studies have shown similar improved outcomes for CD patients with early treatment.

The study findings were limited by several factors including the retrospective design and lack of power to compare long-term progression-free survival, the researchers noted. However, the results were strengthened by the robust data on hospitalizations and surgeries from the TAILORIX trial.

The results support a more flexible strategy for CD, “recommending endoscopic and clinical remission in early diagnosed patients and less stringent objectives in those with more refractory or advanced disease,” they concluded.
 

Findings may guide patient management

The current study is important to help clinicians know whether CD patients who achieve a short-term, steroid-free clinical and endoscopic remission go on to experience better long-term disease outcomes than those who do not achieve this short-term remission, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.

Dr. Sakuraba said that he was surprised by the study findings. “Achieving a clinical remission off steroids with complete endoscopic remission, i.e., deep remission, is considered a treatment goal, but the fact that it did not result in less disease progression was surprising.”

The take-home message for clinicians from the study is that CD patients may still experience disease progression after achieving a single time of clinical and endoscopic remission “mainly due to loss of response to infliximab, so continued long-term disease monitoring and control are required,” Dr. Sakuraba said.

The current study was a post hoc follow-up analysis of a previous trial, Dr. Sakuraba noted. Therefore, studies primarily focused on changing the disease progression and natural course of CD are warranted.

Dr. Laharie disclosed counseling, boards, transportation, or fees from AbbVie, Biogaran, Biogen, Ferring, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda, Theradiag, and Tillots. Dr. Sakuraba had no relevant financial conflicts to disclose.

This article was updated Feb. 10, 2022.

Achieving steroid-free clinical and endoscopic remission does not decrease the risk of Crohn’s disease progression measured by surgery, hospitalization, or initiation of new treatments, according to a post hoc analysis of data from a prospective RCT.

The therapeutic goals of Crohn’s disease have evolved from controlling symptoms to blocking disease progression and reducing complications, wrote David Laharie, MD, of Hôpital Haut-Lévêque, Pessac, France, and colleagues. The goal of steroid-free remission has been used as an endpoint of treatment, but data on the impact of such remission on long-term disease are limited, the researchers noted in a retrospective study published in Clinical Gastroenterology and Hepatology.

undefined undefined/iStock/Getty Images

In the study, the researchers reviewed data from 95 adults with early Crohn’s disease (CD) who participated in the TAILORIX trial involving treatment with infliximab and immunomodulators. The primary endpoint of the TAILORIX trial was sustained corticosteroid-free remission from week 22 to 54. In the current study, the primary endpoint was progression-free survival at 1, 3, and 5 years in patients who did or did not meet the TAILORIX primary endpoint. The median disease duration was 4.5 months, and the median follow-up was 64.2 months.

Progression-free survival was defined as a composite of luminal surgery, anal surgery, hospitalization, and the need for a new CD treatment during the follow-up period.

In the study population, 45 patients achieved corticosteroid-free remission and 50 did not. At 54 weeks, 17 patients with corticosteroid-free remission (38%) and 28 patients without remission (56%) achieved complete mucosal healing, and progression-free survival rates were similar between these groups.

Overall, the rates of progression-free survival at 1, 3, and 5 years were not significantly different between the remission and nonremission groups: 86% versus 91%, respectively, at 1 year; 70% for both groups at 3 years; and 64% and 61%, respectively, at 5 years.

The researchers also compared individual components of the primary endpoint (luminal surgery, anal surgery, hospitalization, and the need for a new CD treatment), and found no significant differences in survival rates in patients who had and had not achieved steroid-free remission.

Survival rates without luminal surgery at 1, 3, and 5 years were 97% versus 96%, 93% versus 90%, and 87% versus 82%, respectively, for remission and nonremission groups. Similarly, survival rates without anal surgery were 93%, 86%, and 86% versus 96%, 88%, and 85%, respectively, for the two groups. Rates of hospitalization-free survival at 1, 3, and 5 years were 90% versus 92%, 81% versus 81%, and 78% versus 69%, respectively, in the remission and nonremission groups. Survival rates without a new systemic CD treatment also were similar at 1, 3, and 5 years: 93% versus 95%, 71% versus 93%, and 60% versus 51%, respectively, for the remission and nonremission groups.

CD progression was not associated with not achieving corticosteroid-free remission (hazard ratio, 0.861). Other factors that were not associated with disease progression in this study included CRP greater than 5 mg/L, age older than 30 years, active smoking, and B1 phenotype.

The researchers noted that, although endoscopic and clinical remission is currently recommended for CD, “there is no validated or standardized definition of this endoscopic goal.” The high rates of survival without major abdominal surgery, regardless of remission status, suggest a significant impact of early combination therapy for CD patients who were biologic naive. Other studies have shown similar improved outcomes for CD patients with early treatment.

The study findings were limited by several factors including the retrospective design and lack of power to compare long-term progression-free survival, the researchers noted. However, the results were strengthened by the robust data on hospitalizations and surgeries from the TAILORIX trial.

The results support a more flexible strategy for CD, “recommending endoscopic and clinical remission in early diagnosed patients and less stringent objectives in those with more refractory or advanced disease,” they concluded.
 

Findings may guide patient management

The current study is important to help clinicians know whether CD patients who achieve a short-term, steroid-free clinical and endoscopic remission go on to experience better long-term disease outcomes than those who do not achieve this short-term remission, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.

Dr. Sakuraba said that he was surprised by the study findings. “Achieving a clinical remission off steroids with complete endoscopic remission, i.e., deep remission, is considered a treatment goal, but the fact that it did not result in less disease progression was surprising.”

The take-home message for clinicians from the study is that CD patients may still experience disease progression after achieving a single time of clinical and endoscopic remission “mainly due to loss of response to infliximab, so continued long-term disease monitoring and control are required,” Dr. Sakuraba said.

The current study was a post hoc follow-up analysis of a previous trial, Dr. Sakuraba noted. Therefore, studies primarily focused on changing the disease progression and natural course of CD are warranted.

Dr. Laharie disclosed counseling, boards, transportation, or fees from AbbVie, Biogaran, Biogen, Ferring, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda, Theradiag, and Tillots. Dr. Sakuraba had no relevant financial conflicts to disclose.

This article was updated Feb. 10, 2022.

Achieving steroid-free clinical and endoscopic remission does not decrease the risk of Crohn’s disease progression measured by surgery, hospitalization, or initiation of new treatments, according to a post hoc analysis of data from a prospective RCT.

The therapeutic goals of Crohn’s disease have evolved from controlling symptoms to blocking disease progression and reducing complications, wrote David Laharie, MD, of Hôpital Haut-Lévêque, Pessac, France, and colleagues. The goal of steroid-free remission has been used as an endpoint of treatment, but data on the impact of such remission on long-term disease are limited, the researchers noted in a retrospective study published in Clinical Gastroenterology and Hepatology.

undefined undefined/iStock/Getty Images

In the study, the researchers reviewed data from 95 adults with early Crohn’s disease (CD) who participated in the TAILORIX trial involving treatment with infliximab and immunomodulators. The primary endpoint of the TAILORIX trial was sustained corticosteroid-free remission from week 22 to 54. In the current study, the primary endpoint was progression-free survival at 1, 3, and 5 years in patients who did or did not meet the TAILORIX primary endpoint. The median disease duration was 4.5 months, and the median follow-up was 64.2 months.

Progression-free survival was defined as a composite of luminal surgery, anal surgery, hospitalization, and the need for a new CD treatment during the follow-up period.

In the study population, 45 patients achieved corticosteroid-free remission and 50 did not. At 54 weeks, 17 patients with corticosteroid-free remission (38%) and 28 patients without remission (56%) achieved complete mucosal healing, and progression-free survival rates were similar between these groups.

Overall, the rates of progression-free survival at 1, 3, and 5 years were not significantly different between the remission and nonremission groups: 86% versus 91%, respectively, at 1 year; 70% for both groups at 3 years; and 64% and 61%, respectively, at 5 years.

The researchers also compared individual components of the primary endpoint (luminal surgery, anal surgery, hospitalization, and the need for a new CD treatment), and found no significant differences in survival rates in patients who had and had not achieved steroid-free remission.

Survival rates without luminal surgery at 1, 3, and 5 years were 97% versus 96%, 93% versus 90%, and 87% versus 82%, respectively, for remission and nonremission groups. Similarly, survival rates without anal surgery were 93%, 86%, and 86% versus 96%, 88%, and 85%, respectively, for the two groups. Rates of hospitalization-free survival at 1, 3, and 5 years were 90% versus 92%, 81% versus 81%, and 78% versus 69%, respectively, in the remission and nonremission groups. Survival rates without a new systemic CD treatment also were similar at 1, 3, and 5 years: 93% versus 95%, 71% versus 93%, and 60% versus 51%, respectively, for the remission and nonremission groups.

CD progression was not associated with not achieving corticosteroid-free remission (hazard ratio, 0.861). Other factors that were not associated with disease progression in this study included CRP greater than 5 mg/L, age older than 30 years, active smoking, and B1 phenotype.

The researchers noted that, although endoscopic and clinical remission is currently recommended for CD, “there is no validated or standardized definition of this endoscopic goal.” The high rates of survival without major abdominal surgery, regardless of remission status, suggest a significant impact of early combination therapy for CD patients who were biologic naive. Other studies have shown similar improved outcomes for CD patients with early treatment.

The study findings were limited by several factors including the retrospective design and lack of power to compare long-term progression-free survival, the researchers noted. However, the results were strengthened by the robust data on hospitalizations and surgeries from the TAILORIX trial.

The results support a more flexible strategy for CD, “recommending endoscopic and clinical remission in early diagnosed patients and less stringent objectives in those with more refractory or advanced disease,” they concluded.
 

Findings may guide patient management

The current study is important to help clinicians know whether CD patients who achieve a short-term, steroid-free clinical and endoscopic remission go on to experience better long-term disease outcomes than those who do not achieve this short-term remission, Atsushi Sakuraba, MD, of the University of Chicago said in an interview.

Dr. Sakuraba said that he was surprised by the study findings. “Achieving a clinical remission off steroids with complete endoscopic remission, i.e., deep remission, is considered a treatment goal, but the fact that it did not result in less disease progression was surprising.”

The take-home message for clinicians from the study is that CD patients may still experience disease progression after achieving a single time of clinical and endoscopic remission “mainly due to loss of response to infliximab, so continued long-term disease monitoring and control are required,” Dr. Sakuraba said.

The current study was a post hoc follow-up analysis of a previous trial, Dr. Sakuraba noted. Therefore, studies primarily focused on changing the disease progression and natural course of CD are warranted.

Dr. Laharie disclosed counseling, boards, transportation, or fees from AbbVie, Biogaran, Biogen, Ferring, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda, Theradiag, and Tillots. Dr. Sakuraba had no relevant financial conflicts to disclose.

This article was updated Feb. 10, 2022.

Recalls and false-positives for breast imaging patients were significantly more likely when the results were read by less-experienced radiologists who had worked more hours that day, based on data from more than 97,000 screening mammograms.

Psychology literature has shown the impact of fatigue on performance in a range of settings, and previous studies have shown that radiologists’ performances are more accurate earlier in their shifts compared to later-shift performance, write Michael H. Bernstein, PhD, and colleagues at Brown University, Providence, R.I., in a study published online Jan. 11 in Radiology.

The effect of time of day on performance may be greater for more detailed imaging modalities that are more “cognitively taxing,” and the effect may be greater in less-experienced radiologists, but the impact of time and experience on overall patient recall and false-positive rates has not been well-studied, the researchers said.

In the retrospective review, the researchers identified 97,671 screening mammograms read by 18 radiologists at one of 12 community sites between Jan. 2018 and Dec. 2019. The researchers analyzed the results by type of image, either standard digital mammography (DM) or the more complex digital breast tomosynthesis (DBT). The researchers separated radiologists into two groups: those with at least 5 post-training years of experience and those with less than 5 post-training years of experience. A total of nine radiologists fell into each category.

Overall, the recall rates were significantly different and higher for DM versus DBT (10.2% vs. 9.0%; P = .006). The false-positive (FP) rate also differed significantly and was higher for DM versus DBT (9.8% vs. 8.6%; P = .004).

The odds of recall increased by 11.5% with each hour of reading time for radiologists with less than 5 post-training years of experience for both DBT (odds ratio, 1.12) and DM (OR, 1.09). For the more experienced radiologists, the odds of recall increased by 1.6% for each hour of reading time for DBT but decreased by 0.1% for DM, with no significant difference.

Similarly, the odds of an FP result increased by 12.1% for DBT and 9% for DM per hour of reading time for radiologists with less experience. For more experienced radiologists, the odds of an FP increased by 1.6% for DBT but decreased by 1.1% for DM per hour of reading time.

Cancer detection (defined as true-positive, or TP) was not higher for DM across time, the researchers note. However, “DBT achieved a higher TP rate than DM regardless of the time of day; this shows that for DBT to maintain a constant and superior TP rate relative to DM, radiologists’ FP rates had to go up as the day went on,” they write. “That is, although DBT achieves a superior TP rate, more junior radiologists appeared to compensate for their fatigue later in the day when using DBT by recalling a broader range of mammograms, more of which were FP findings.”

The researchers caution that their findings were limited by several factors, including the study’s retrospective design and the lack of randomization of the imaging technology, patients, and time of day, which prohibit conclusions regarding causality. Other limitations included the consideration of time of day without the ability to use hours since the start of a clinical shift and the use of a 5-year mark to indicate experience without accounting for work volume.

However, the stronger impact of a time-of-day effect for more junior radiologists agrees with findings from other studies, the researchers add. More empirical research is needed, and the researchers propose a longitudinal study of how time of day affects radiologists as they gain experience, as well as experimental studies to test strategies for mitigating the time-of-day effect observed in the current study.
 

Scheduled breaks may reduce impact of fatigue

“Digital breast tomosynthesis is increasingly used in clinical practice and takes significantly longer to interpret compared with digital mammography,” said corresponding author Ana P. Lourenco, MD, in an interview. “Radiologists interpret hundreds of images for each screening digital breast tomosynthesis exam, compared with four images for each screening digital mammogram exam; this may certainly contribute to radiologist fatigue.”

“I found it interesting that there was a difference based on years of experience of the radiologist, but I was not surprised that recall rate increased later in the day, as some of us had anecdotally noted this in our clinical practice,” Dr. Lourenco said. In fact, the idea to conduct the study was prompted by a conversation with her statistician colleagues “about how I subjectively felt like my own recall rate increased at the end of the day.”

Ways to counteract the impact of fatigue could include intermittent breaks to refocus attention, said Dr. Lourenco. “Potential barriers would include imaging volumes and attending to patients in the breast imaging center,” she said. “If we can show that decreasing fatigue improves mammography performance metrics, then this may encourage practices to support such interventions.”

However, “more research that includes a larger number of radiologists, wider range of imaging interpretation experience, perhaps even experimental studies comparing metrics for radiologists reading with scheduled breaks versus without such breaks would be of interest,” Dr. Lourenco said.
 

Fatigue in health care goes beyond radiology

“Due primarily to staffing shortages and increased volume and complexity of patients, burnout and fatigue of all medical personnel, not just physicians, have become hallmarks of modern health care delivery in the United States, and this has been exacerbated by COVID-19 and other societal factors,” said Jeffrey C. Weinreb, MD, professor of radiology and biomedical imaging at Yale University, New Haven, Conn., in an interview.

Previous studies have documented the fact that radiologists are among the specialists most affected by burnout and fatigue, and it has an impact on their performance, Dr. Weinreb said. The current study is important because it tries to pinpoint the key variables that are responsible for fatigue, so resources can be directed to effect change, he said.

Dr. Weinreb said he was not particularly surprised by the study findings. “Diagnostic mammography is a high-volume repetitive enterprise, so it would have been surprising if radiologist experience and time of day had no effect on performance and recall rate,” he said. “As most radiologists will attest based on personal experience, human beings get tired and lose some level of cognition over the course of a long, intense workday,” he added.

“I am a bit surprised that less experienced radiologists were more likely to recommend additional imaging at a higher rate when interpreting DBT but not for DM and only later in the day,” Dr. Weinreb noted. “The authors suggest that this could be due to the increased number of images that are viewed with DBT and the different ways experienced and less experienced radiologists process the information. However, there could be other explanations, such as differences in volumes or differences in ages.”

“Reducing the study volumes per radiologist is one obvious solution to reducing fatigue, but it will not be practical in many practices,” said Dr. Weinreb. “The important work of interpreting diagnostic mammograms needs to continue and grow. Without an increase in radiologist mammographers in the labor pool, this is not going to happen any time soon.”

Instead, “more immediate obvious solutions to radiologist fatigue in clinical practice include more frequent breaks during the workday, which would include walking around and not looking at a computer or cell phone screen, fewer images per study, report templates, streamlined workflow, more variety in daily work, and AI assistance for interpretation and reporting,” said Dr. Weinreb. Using nonradiologists when possible to relieve some of the burden could be considered, “but this is a complex and politically charged issue,” he noted.

Radiology is a well-compensated specialty, but further increasing compensation would help to mitigate burnout, said Dr. Weinreb. However, “perhaps even more important is making certain that the efforts of individual radiologists are appreciated and recognized,” he said.

As for additional research needs, “mammographers are not the only radiologists experiencing fatigue, but the most critical contributing factors for other types of imaging exams and subspecialities may not be identical,” Dr. Weinreb emphasized. “Data for other radiologists, similar to that provided by this study for diagnostic mammography, could be useful.

“An additional area of research could address the issue of individual radiologist circadian rhythms,” said Dr. Weinreb. “Perhaps we could rigorously determine whom amongst us is a ‘morning person’ versus one who performs equally well or better later in the day and use this information for radiologist scheduling,” he said. “Finally, once we know the key factors affecting performance for each type of exam and subspecialty, studies of possible incremental and combined benefits of various interventions would be needed.”

The study received no outside funding. The researchers and Dr. Weinreb have disclosed no relevant financial relationships.

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

Recalls and false-positives for breast imaging patients were significantly more likely when the results were read by less-experienced radiologists who had worked more hours that day, based on data from more than 97,000 screening mammograms.

Psychology literature has shown the impact of fatigue on performance in a range of settings, and previous studies have shown that radiologists’ performances are more accurate earlier in their shifts compared to later-shift performance, write Michael H. Bernstein, PhD, and colleagues at Brown University, Providence, R.I., in a study published online Jan. 11 in Radiology.

The effect of time of day on performance may be greater for more detailed imaging modalities that are more “cognitively taxing,” and the effect may be greater in less-experienced radiologists, but the impact of time and experience on overall patient recall and false-positive rates has not been well-studied, the researchers said.

In the retrospective review, the researchers identified 97,671 screening mammograms read by 18 radiologists at one of 12 community sites between Jan. 2018 and Dec. 2019. The researchers analyzed the results by type of image, either standard digital mammography (DM) or the more complex digital breast tomosynthesis (DBT). The researchers separated radiologists into two groups: those with at least 5 post-training years of experience and those with less than 5 post-training years of experience. A total of nine radiologists fell into each category.

Overall, the recall rates were significantly different and higher for DM versus DBT (10.2% vs. 9.0%; P = .006). The false-positive (FP) rate also differed significantly and was higher for DM versus DBT (9.8% vs. 8.6%; P = .004).

The odds of recall increased by 11.5% with each hour of reading time for radiologists with less than 5 post-training years of experience for both DBT (odds ratio, 1.12) and DM (OR, 1.09). For the more experienced radiologists, the odds of recall increased by 1.6% for each hour of reading time for DBT but decreased by 0.1% for DM, with no significant difference.

Similarly, the odds of an FP result increased by 12.1% for DBT and 9% for DM per hour of reading time for radiologists with less experience. For more experienced radiologists, the odds of an FP increased by 1.6% for DBT but decreased by 1.1% for DM per hour of reading time.

Cancer detection (defined as true-positive, or TP) was not higher for DM across time, the researchers note. However, “DBT achieved a higher TP rate than DM regardless of the time of day; this shows that for DBT to maintain a constant and superior TP rate relative to DM, radiologists’ FP rates had to go up as the day went on,” they write. “That is, although DBT achieves a superior TP rate, more junior radiologists appeared to compensate for their fatigue later in the day when using DBT by recalling a broader range of mammograms, more of which were FP findings.”

The researchers caution that their findings were limited by several factors, including the study’s retrospective design and the lack of randomization of the imaging technology, patients, and time of day, which prohibit conclusions regarding causality. Other limitations included the consideration of time of day without the ability to use hours since the start of a clinical shift and the use of a 5-year mark to indicate experience without accounting for work volume.

However, the stronger impact of a time-of-day effect for more junior radiologists agrees with findings from other studies, the researchers add. More empirical research is needed, and the researchers propose a longitudinal study of how time of day affects radiologists as they gain experience, as well as experimental studies to test strategies for mitigating the time-of-day effect observed in the current study.
 

Scheduled breaks may reduce impact of fatigue

“Digital breast tomosynthesis is increasingly used in clinical practice and takes significantly longer to interpret compared with digital mammography,” said corresponding author Ana P. Lourenco, MD, in an interview. “Radiologists interpret hundreds of images for each screening digital breast tomosynthesis exam, compared with four images for each screening digital mammogram exam; this may certainly contribute to radiologist fatigue.”

“I found it interesting that there was a difference based on years of experience of the radiologist, but I was not surprised that recall rate increased later in the day, as some of us had anecdotally noted this in our clinical practice,” Dr. Lourenco said. In fact, the idea to conduct the study was prompted by a conversation with her statistician colleagues “about how I subjectively felt like my own recall rate increased at the end of the day.”

Ways to counteract the impact of fatigue could include intermittent breaks to refocus attention, said Dr. Lourenco. “Potential barriers would include imaging volumes and attending to patients in the breast imaging center,” she said. “If we can show that decreasing fatigue improves mammography performance metrics, then this may encourage practices to support such interventions.”

However, “more research that includes a larger number of radiologists, wider range of imaging interpretation experience, perhaps even experimental studies comparing metrics for radiologists reading with scheduled breaks versus without such breaks would be of interest,” Dr. Lourenco said.
 

Fatigue in health care goes beyond radiology

“Due primarily to staffing shortages and increased volume and complexity of patients, burnout and fatigue of all medical personnel, not just physicians, have become hallmarks of modern health care delivery in the United States, and this has been exacerbated by COVID-19 and other societal factors,” said Jeffrey C. Weinreb, MD, professor of radiology and biomedical imaging at Yale University, New Haven, Conn., in an interview.

Previous studies have documented the fact that radiologists are among the specialists most affected by burnout and fatigue, and it has an impact on their performance, Dr. Weinreb said. The current study is important because it tries to pinpoint the key variables that are responsible for fatigue, so resources can be directed to effect change, he said.

Dr. Weinreb said he was not particularly surprised by the study findings. “Diagnostic mammography is a high-volume repetitive enterprise, so it would have been surprising if radiologist experience and time of day had no effect on performance and recall rate,” he said. “As most radiologists will attest based on personal experience, human beings get tired and lose some level of cognition over the course of a long, intense workday,” he added.

“I am a bit surprised that less experienced radiologists were more likely to recommend additional imaging at a higher rate when interpreting DBT but not for DM and only later in the day,” Dr. Weinreb noted. “The authors suggest that this could be due to the increased number of images that are viewed with DBT and the different ways experienced and less experienced radiologists process the information. However, there could be other explanations, such as differences in volumes or differences in ages.”

“Reducing the study volumes per radiologist is one obvious solution to reducing fatigue, but it will not be practical in many practices,” said Dr. Weinreb. “The important work of interpreting diagnostic mammograms needs to continue and grow. Without an increase in radiologist mammographers in the labor pool, this is not going to happen any time soon.”

Instead, “more immediate obvious solutions to radiologist fatigue in clinical practice include more frequent breaks during the workday, which would include walking around and not looking at a computer or cell phone screen, fewer images per study, report templates, streamlined workflow, more variety in daily work, and AI assistance for interpretation and reporting,” said Dr. Weinreb. Using nonradiologists when possible to relieve some of the burden could be considered, “but this is a complex and politically charged issue,” he noted.

Radiology is a well-compensated specialty, but further increasing compensation would help to mitigate burnout, said Dr. Weinreb. However, “perhaps even more important is making certain that the efforts of individual radiologists are appreciated and recognized,” he said.

As for additional research needs, “mammographers are not the only radiologists experiencing fatigue, but the most critical contributing factors for other types of imaging exams and subspecialities may not be identical,” Dr. Weinreb emphasized. “Data for other radiologists, similar to that provided by this study for diagnostic mammography, could be useful.

“An additional area of research could address the issue of individual radiologist circadian rhythms,” said Dr. Weinreb. “Perhaps we could rigorously determine whom amongst us is a ‘morning person’ versus one who performs equally well or better later in the day and use this information for radiologist scheduling,” he said. “Finally, once we know the key factors affecting performance for each type of exam and subspecialty, studies of possible incremental and combined benefits of various interventions would be needed.”

The study received no outside funding. The researchers and Dr. Weinreb have disclosed no relevant financial relationships.

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

Recalls and false-positives for breast imaging patients were significantly more likely when the results were read by less-experienced radiologists who had worked more hours that day, based on data from more than 97,000 screening mammograms.

Psychology literature has shown the impact of fatigue on performance in a range of settings, and previous studies have shown that radiologists’ performances are more accurate earlier in their shifts compared to later-shift performance, write Michael H. Bernstein, PhD, and colleagues at Brown University, Providence, R.I., in a study published online Jan. 11 in Radiology.

The effect of time of day on performance may be greater for more detailed imaging modalities that are more “cognitively taxing,” and the effect may be greater in less-experienced radiologists, but the impact of time and experience on overall patient recall and false-positive rates has not been well-studied, the researchers said.

In the retrospective review, the researchers identified 97,671 screening mammograms read by 18 radiologists at one of 12 community sites between Jan. 2018 and Dec. 2019. The researchers analyzed the results by type of image, either standard digital mammography (DM) or the more complex digital breast tomosynthesis (DBT). The researchers separated radiologists into two groups: those with at least 5 post-training years of experience and those with less than 5 post-training years of experience. A total of nine radiologists fell into each category.

Overall, the recall rates were significantly different and higher for DM versus DBT (10.2% vs. 9.0%; P = .006). The false-positive (FP) rate also differed significantly and was higher for DM versus DBT (9.8% vs. 8.6%; P = .004).

The odds of recall increased by 11.5% with each hour of reading time for radiologists with less than 5 post-training years of experience for both DBT (odds ratio, 1.12) and DM (OR, 1.09). For the more experienced radiologists, the odds of recall increased by 1.6% for each hour of reading time for DBT but decreased by 0.1% for DM, with no significant difference.

Similarly, the odds of an FP result increased by 12.1% for DBT and 9% for DM per hour of reading time for radiologists with less experience. For more experienced radiologists, the odds of an FP increased by 1.6% for DBT but decreased by 1.1% for DM per hour of reading time.

Cancer detection (defined as true-positive, or TP) was not higher for DM across time, the researchers note. However, “DBT achieved a higher TP rate than DM regardless of the time of day; this shows that for DBT to maintain a constant and superior TP rate relative to DM, radiologists’ FP rates had to go up as the day went on,” they write. “That is, although DBT achieves a superior TP rate, more junior radiologists appeared to compensate for their fatigue later in the day when using DBT by recalling a broader range of mammograms, more of which were FP findings.”

The researchers caution that their findings were limited by several factors, including the study’s retrospective design and the lack of randomization of the imaging technology, patients, and time of day, which prohibit conclusions regarding causality. Other limitations included the consideration of time of day without the ability to use hours since the start of a clinical shift and the use of a 5-year mark to indicate experience without accounting for work volume.

However, the stronger impact of a time-of-day effect for more junior radiologists agrees with findings from other studies, the researchers add. More empirical research is needed, and the researchers propose a longitudinal study of how time of day affects radiologists as they gain experience, as well as experimental studies to test strategies for mitigating the time-of-day effect observed in the current study.
 

Scheduled breaks may reduce impact of fatigue

“Digital breast tomosynthesis is increasingly used in clinical practice and takes significantly longer to interpret compared with digital mammography,” said corresponding author Ana P. Lourenco, MD, in an interview. “Radiologists interpret hundreds of images for each screening digital breast tomosynthesis exam, compared with four images for each screening digital mammogram exam; this may certainly contribute to radiologist fatigue.”

“I found it interesting that there was a difference based on years of experience of the radiologist, but I was not surprised that recall rate increased later in the day, as some of us had anecdotally noted this in our clinical practice,” Dr. Lourenco said. In fact, the idea to conduct the study was prompted by a conversation with her statistician colleagues “about how I subjectively felt like my own recall rate increased at the end of the day.”

Ways to counteract the impact of fatigue could include intermittent breaks to refocus attention, said Dr. Lourenco. “Potential barriers would include imaging volumes and attending to patients in the breast imaging center,” she said. “If we can show that decreasing fatigue improves mammography performance metrics, then this may encourage practices to support such interventions.”

However, “more research that includes a larger number of radiologists, wider range of imaging interpretation experience, perhaps even experimental studies comparing metrics for radiologists reading with scheduled breaks versus without such breaks would be of interest,” Dr. Lourenco said.
 

Fatigue in health care goes beyond radiology

“Due primarily to staffing shortages and increased volume and complexity of patients, burnout and fatigue of all medical personnel, not just physicians, have become hallmarks of modern health care delivery in the United States, and this has been exacerbated by COVID-19 and other societal factors,” said Jeffrey C. Weinreb, MD, professor of radiology and biomedical imaging at Yale University, New Haven, Conn., in an interview.

Previous studies have documented the fact that radiologists are among the specialists most affected by burnout and fatigue, and it has an impact on their performance, Dr. Weinreb said. The current study is important because it tries to pinpoint the key variables that are responsible for fatigue, so resources can be directed to effect change, he said.

Dr. Weinreb said he was not particularly surprised by the study findings. “Diagnostic mammography is a high-volume repetitive enterprise, so it would have been surprising if radiologist experience and time of day had no effect on performance and recall rate,” he said. “As most radiologists will attest based on personal experience, human beings get tired and lose some level of cognition over the course of a long, intense workday,” he added.

“I am a bit surprised that less experienced radiologists were more likely to recommend additional imaging at a higher rate when interpreting DBT but not for DM and only later in the day,” Dr. Weinreb noted. “The authors suggest that this could be due to the increased number of images that are viewed with DBT and the different ways experienced and less experienced radiologists process the information. However, there could be other explanations, such as differences in volumes or differences in ages.”

“Reducing the study volumes per radiologist is one obvious solution to reducing fatigue, but it will not be practical in many practices,” said Dr. Weinreb. “The important work of interpreting diagnostic mammograms needs to continue and grow. Without an increase in radiologist mammographers in the labor pool, this is not going to happen any time soon.”

Instead, “more immediate obvious solutions to radiologist fatigue in clinical practice include more frequent breaks during the workday, which would include walking around and not looking at a computer or cell phone screen, fewer images per study, report templates, streamlined workflow, more variety in daily work, and AI assistance for interpretation and reporting,” said Dr. Weinreb. Using nonradiologists when possible to relieve some of the burden could be considered, “but this is a complex and politically charged issue,” he noted.

Radiology is a well-compensated specialty, but further increasing compensation would help to mitigate burnout, said Dr. Weinreb. However, “perhaps even more important is making certain that the efforts of individual radiologists are appreciated and recognized,” he said.

As for additional research needs, “mammographers are not the only radiologists experiencing fatigue, but the most critical contributing factors for other types of imaging exams and subspecialities may not be identical,” Dr. Weinreb emphasized. “Data for other radiologists, similar to that provided by this study for diagnostic mammography, could be useful.

“An additional area of research could address the issue of individual radiologist circadian rhythms,” said Dr. Weinreb. “Perhaps we could rigorously determine whom amongst us is a ‘morning person’ versus one who performs equally well or better later in the day and use this information for radiologist scheduling,” he said. “Finally, once we know the key factors affecting performance for each type of exam and subspecialty, studies of possible incremental and combined benefits of various interventions would be needed.”

The study received no outside funding. The researchers and Dr. Weinreb have disclosed no relevant financial relationships.

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

An intensive weight-loss intervention prior to conception had no effect on birth rates in women with obesity and unexplained infertility, compared with a standard weight-maintenance program, based on data from nearly 400 women.

Obese women experiencing infertility are often counseled to lose weight before attempting fertility treatments in order to improve outcomes based on epidemiologic evidence of an association between obesity and infertility, but data to support this advice are limited, wrote Richard S. Legro, MD, of Penn State University, Hershey, and colleagues.

The researchers proposed that a more intensive preconception weight loss intervention followed by infertility treatment would be more likely to yield a healthy live birth, compared with a standard weight maintenance intervention.

In an open-label study published in PLOS Medicine, the researchers randomized 379 women at nine academic centers to a standard lifestyle group that followed a weight-maintenance plan focused on physical activity, but not weight loss; or an intensive intervention of diet and medication with a target weight loss of 7%. Both interventions lasted for 16 weeks between July 2015 and July 2018. After the interventions, patients in both groups underwent standardized empiric fertility treatment with three cycles of ovarian stimulation and intrauterine insemination.

The primary outcome was a live birth at 37 weeks’ gestation or later, with no congenital abnormalities and a birth weight between 2,500 g and 4,000 g. Baseline characteristics including age, education level, race, and body mass index (BMI) were similar between the groups.

The incidence of healthy live births was not significantly different between the standard treatment and intensive treatment groups (15.2% vs. 12.2%; P = 0.40) by the final follow-up time of September 2019. However, women in the intensive group had significantly greater weight loss, compared with the standard group (–6.6% vs. –0.3%; P < .001). Women in the intensive group also showed improvements in metabolic health. Notably, the incidence of metabolic syndrome dropped from 53.6% to 49.4% in the standard group, compared with a decrease from 52.8% to 32.2% in the intensive group over the 16-week study period, the researchers wrote.

Gastrointestinal side effects were significantly more common in the intensive group, but these were consistent with documented side effects of the weight loss medication used (Orlistat).

First-trimester pregnancy loss was higher in the intensive group, compared with the standard group (33.3% vs. 23.7%), but the difference was not significant. Most pregnancy complications, including preterm labor, premature rupture of membranes, preeclampsia, and gestational diabetes had nonsignificant improvements in the intensive group, compared with the standard group. Similarly, nonsignificant improvements were noted in the intervention group for intrauterine growth restriction and admission to the neonatal ICU.

Limitations of the study included the relatively small number of pregnancies, which prevented assessment of rare complications in subgroups, and the challenge of matching control interventions, the researchers noted.

However, the results were strengthened by the focus on women with unexplained infertility, the inclusion of a comparison group, and the collection of data on complications after conception, they wrote.

Avenues for future research include interventions of different duration and intensity prior to conception, which may improve outcomes, the researchers said in their discussion of the findings. “A period of weight stabilization and maintenance after a weight-loss intervention prior to commencing infertility therapy is worth exploring,” they noted, but couples eager to conceive may be reluctant to wait for a weight-loss intervention, they added.

“Our findings directly impact current standards of clinical care, where women who are obese with unexplained infertility are to our knowledge routinely counseled to lose weight prior to initiation of infertility treatment,” they concluded.
 

Data may inform patient discussions

The current study is important because a large amount of previous research has shown an association between obesity and decreased fecundity in women and men, Mark P. Trolice, MD, of the University of Central Florida, Orlando, and director of the IVF Center in Winter Park, Fla., said in an interview.

According to the Centers for Disease Control and Prevention, the prevalence of obesity in the United States remains more than 40%, said Dr. Trolice. “Patients and physicians would benefit from clarity of obesity’s effect, if any, on reproduction,” he noted.

In contrast to the authors’ hypothesis, “the study did not find a difference in the live birth rate following up to three cycles of intrauterine insemination (IUI) between an intensive weight loss group [and] women who exercised without weight loss,” said Dr. Trolice. “Prior to this study, many reports suggested a decline in fertility with elevations in BMI, particularly during fertility treatment,” he added.

The take-home message from the current study is a that an elevated BMI, while possibly increasing the risks of metabolic disorders, did not appear to impact fecundity, he said.

The authors therefore concluded, “There is not strong evidence to recommend weight loss prior to conception in women who are obese with unexplained infertility,” Dr. Trolice said.

Regardless of the potential effect of preconception weight loss on fertility, barriers to starting a weight loss program include a woman’s eagerness to move forward with fertility treatments without waiting for weight loss, Dr. Trolice noted. “By the time a woman reaches an infertility specialist, she has been trying to conceive for at least 1 year,” he said. “At the initial consultation, these patients are anxious to undergo necessary additional diagnostic testing followed by treatment. Consequently, initiation of a weight-loss program is viewed as a delay toward the goal of family building,” he explained.

“More research is needed to demonstrate the safety of intensive weight loss preconception,” said Dr. Trolice. However, he said, “the issue of elevated BMI and increased risk of pregnancy complications remains, but this study provides important information for providers regarding counseling their patients desiring pregnancy.”

The study was supported by multiple grants from the National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Nutrisystem provided discounted coupons for food allotments in the standardized treatment group, and FitBit provided the study organizers with discounted Fitbits for activity monitoring. Lead author Dr. Legro disclosed consulting fees from InSupp, Ferring, Bayer, Abbvie and Fractyl, and research sponsorship from Guerbet and the National Institutes of Health. Dr. Trolice had no financial conflicts to disclose and serves on the Editorial Advisory Board of Ob.Gyn News.

An intensive weight-loss intervention prior to conception had no effect on birth rates in women with obesity and unexplained infertility, compared with a standard weight-maintenance program, based on data from nearly 400 women.

Obese women experiencing infertility are often counseled to lose weight before attempting fertility treatments in order to improve outcomes based on epidemiologic evidence of an association between obesity and infertility, but data to support this advice are limited, wrote Richard S. Legro, MD, of Penn State University, Hershey, and colleagues.

The researchers proposed that a more intensive preconception weight loss intervention followed by infertility treatment would be more likely to yield a healthy live birth, compared with a standard weight maintenance intervention.

In an open-label study published in PLOS Medicine, the researchers randomized 379 women at nine academic centers to a standard lifestyle group that followed a weight-maintenance plan focused on physical activity, but not weight loss; or an intensive intervention of diet and medication with a target weight loss of 7%. Both interventions lasted for 16 weeks between July 2015 and July 2018. After the interventions, patients in both groups underwent standardized empiric fertility treatment with three cycles of ovarian stimulation and intrauterine insemination.

The primary outcome was a live birth at 37 weeks’ gestation or later, with no congenital abnormalities and a birth weight between 2,500 g and 4,000 g. Baseline characteristics including age, education level, race, and body mass index (BMI) were similar between the groups.

The incidence of healthy live births was not significantly different between the standard treatment and intensive treatment groups (15.2% vs. 12.2%; P = 0.40) by the final follow-up time of September 2019. However, women in the intensive group had significantly greater weight loss, compared with the standard group (–6.6% vs. –0.3%; P < .001). Women in the intensive group also showed improvements in metabolic health. Notably, the incidence of metabolic syndrome dropped from 53.6% to 49.4% in the standard group, compared with a decrease from 52.8% to 32.2% in the intensive group over the 16-week study period, the researchers wrote.

Gastrointestinal side effects were significantly more common in the intensive group, but these were consistent with documented side effects of the weight loss medication used (Orlistat).

First-trimester pregnancy loss was higher in the intensive group, compared with the standard group (33.3% vs. 23.7%), but the difference was not significant. Most pregnancy complications, including preterm labor, premature rupture of membranes, preeclampsia, and gestational diabetes had nonsignificant improvements in the intensive group, compared with the standard group. Similarly, nonsignificant improvements were noted in the intervention group for intrauterine growth restriction and admission to the neonatal ICU.

Limitations of the study included the relatively small number of pregnancies, which prevented assessment of rare complications in subgroups, and the challenge of matching control interventions, the researchers noted.

However, the results were strengthened by the focus on women with unexplained infertility, the inclusion of a comparison group, and the collection of data on complications after conception, they wrote.

Avenues for future research include interventions of different duration and intensity prior to conception, which may improve outcomes, the researchers said in their discussion of the findings. “A period of weight stabilization and maintenance after a weight-loss intervention prior to commencing infertility therapy is worth exploring,” they noted, but couples eager to conceive may be reluctant to wait for a weight-loss intervention, they added.

“Our findings directly impact current standards of clinical care, where women who are obese with unexplained infertility are to our knowledge routinely counseled to lose weight prior to initiation of infertility treatment,” they concluded.
 

Data may inform patient discussions

The current study is important because a large amount of previous research has shown an association between obesity and decreased fecundity in women and men, Mark P. Trolice, MD, of the University of Central Florida, Orlando, and director of the IVF Center in Winter Park, Fla., said in an interview.

According to the Centers for Disease Control and Prevention, the prevalence of obesity in the United States remains more than 40%, said Dr. Trolice. “Patients and physicians would benefit from clarity of obesity’s effect, if any, on reproduction,” he noted.

In contrast to the authors’ hypothesis, “the study did not find a difference in the live birth rate following up to three cycles of intrauterine insemination (IUI) between an intensive weight loss group [and] women who exercised without weight loss,” said Dr. Trolice. “Prior to this study, many reports suggested a decline in fertility with elevations in BMI, particularly during fertility treatment,” he added.

The take-home message from the current study is a that an elevated BMI, while possibly increasing the risks of metabolic disorders, did not appear to impact fecundity, he said.

The authors therefore concluded, “There is not strong evidence to recommend weight loss prior to conception in women who are obese with unexplained infertility,” Dr. Trolice said.

Regardless of the potential effect of preconception weight loss on fertility, barriers to starting a weight loss program include a woman’s eagerness to move forward with fertility treatments without waiting for weight loss, Dr. Trolice noted. “By the time a woman reaches an infertility specialist, she has been trying to conceive for at least 1 year,” he said. “At the initial consultation, these patients are anxious to undergo necessary additional diagnostic testing followed by treatment. Consequently, initiation of a weight-loss program is viewed as a delay toward the goal of family building,” he explained.

“More research is needed to demonstrate the safety of intensive weight loss preconception,” said Dr. Trolice. However, he said, “the issue of elevated BMI and increased risk of pregnancy complications remains, but this study provides important information for providers regarding counseling their patients desiring pregnancy.”

The study was supported by multiple grants from the National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Nutrisystem provided discounted coupons for food allotments in the standardized treatment group, and FitBit provided the study organizers with discounted Fitbits for activity monitoring. Lead author Dr. Legro disclosed consulting fees from InSupp, Ferring, Bayer, Abbvie and Fractyl, and research sponsorship from Guerbet and the National Institutes of Health. Dr. Trolice had no financial conflicts to disclose and serves on the Editorial Advisory Board of Ob.Gyn News.

An intensive weight-loss intervention prior to conception had no effect on birth rates in women with obesity and unexplained infertility, compared with a standard weight-maintenance program, based on data from nearly 400 women.

Obese women experiencing infertility are often counseled to lose weight before attempting fertility treatments in order to improve outcomes based on epidemiologic evidence of an association between obesity and infertility, but data to support this advice are limited, wrote Richard S. Legro, MD, of Penn State University, Hershey, and colleagues.

The researchers proposed that a more intensive preconception weight loss intervention followed by infertility treatment would be more likely to yield a healthy live birth, compared with a standard weight maintenance intervention.

In an open-label study published in PLOS Medicine, the researchers randomized 379 women at nine academic centers to a standard lifestyle group that followed a weight-maintenance plan focused on physical activity, but not weight loss; or an intensive intervention of diet and medication with a target weight loss of 7%. Both interventions lasted for 16 weeks between July 2015 and July 2018. After the interventions, patients in both groups underwent standardized empiric fertility treatment with three cycles of ovarian stimulation and intrauterine insemination.

The primary outcome was a live birth at 37 weeks’ gestation or later, with no congenital abnormalities and a birth weight between 2,500 g and 4,000 g. Baseline characteristics including age, education level, race, and body mass index (BMI) were similar between the groups.

The incidence of healthy live births was not significantly different between the standard treatment and intensive treatment groups (15.2% vs. 12.2%; P = 0.40) by the final follow-up time of September 2019. However, women in the intensive group had significantly greater weight loss, compared with the standard group (–6.6% vs. –0.3%; P < .001). Women in the intensive group also showed improvements in metabolic health. Notably, the incidence of metabolic syndrome dropped from 53.6% to 49.4% in the standard group, compared with a decrease from 52.8% to 32.2% in the intensive group over the 16-week study period, the researchers wrote.

Gastrointestinal side effects were significantly more common in the intensive group, but these were consistent with documented side effects of the weight loss medication used (Orlistat).

First-trimester pregnancy loss was higher in the intensive group, compared with the standard group (33.3% vs. 23.7%), but the difference was not significant. Most pregnancy complications, including preterm labor, premature rupture of membranes, preeclampsia, and gestational diabetes had nonsignificant improvements in the intensive group, compared with the standard group. Similarly, nonsignificant improvements were noted in the intervention group for intrauterine growth restriction and admission to the neonatal ICU.

Limitations of the study included the relatively small number of pregnancies, which prevented assessment of rare complications in subgroups, and the challenge of matching control interventions, the researchers noted.

However, the results were strengthened by the focus on women with unexplained infertility, the inclusion of a comparison group, and the collection of data on complications after conception, they wrote.

Avenues for future research include interventions of different duration and intensity prior to conception, which may improve outcomes, the researchers said in their discussion of the findings. “A period of weight stabilization and maintenance after a weight-loss intervention prior to commencing infertility therapy is worth exploring,” they noted, but couples eager to conceive may be reluctant to wait for a weight-loss intervention, they added.

“Our findings directly impact current standards of clinical care, where women who are obese with unexplained infertility are to our knowledge routinely counseled to lose weight prior to initiation of infertility treatment,” they concluded.
 

Data may inform patient discussions

The current study is important because a large amount of previous research has shown an association between obesity and decreased fecundity in women and men, Mark P. Trolice, MD, of the University of Central Florida, Orlando, and director of the IVF Center in Winter Park, Fla., said in an interview.

According to the Centers for Disease Control and Prevention, the prevalence of obesity in the United States remains more than 40%, said Dr. Trolice. “Patients and physicians would benefit from clarity of obesity’s effect, if any, on reproduction,” he noted.

In contrast to the authors’ hypothesis, “the study did not find a difference in the live birth rate following up to three cycles of intrauterine insemination (IUI) between an intensive weight loss group [and] women who exercised without weight loss,” said Dr. Trolice. “Prior to this study, many reports suggested a decline in fertility with elevations in BMI, particularly during fertility treatment,” he added.

The take-home message from the current study is a that an elevated BMI, while possibly increasing the risks of metabolic disorders, did not appear to impact fecundity, he said.

The authors therefore concluded, “There is not strong evidence to recommend weight loss prior to conception in women who are obese with unexplained infertility,” Dr. Trolice said.

Regardless of the potential effect of preconception weight loss on fertility, barriers to starting a weight loss program include a woman’s eagerness to move forward with fertility treatments without waiting for weight loss, Dr. Trolice noted. “By the time a woman reaches an infertility specialist, she has been trying to conceive for at least 1 year,” he said. “At the initial consultation, these patients are anxious to undergo necessary additional diagnostic testing followed by treatment. Consequently, initiation of a weight-loss program is viewed as a delay toward the goal of family building,” he explained.

“More research is needed to demonstrate the safety of intensive weight loss preconception,” said Dr. Trolice. However, he said, “the issue of elevated BMI and increased risk of pregnancy complications remains, but this study provides important information for providers regarding counseling their patients desiring pregnancy.”

The study was supported by multiple grants from the National Institutes of Health through the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences. Nutrisystem provided discounted coupons for food allotments in the standardized treatment group, and FitBit provided the study organizers with discounted Fitbits for activity monitoring. Lead author Dr. Legro disclosed consulting fees from InSupp, Ferring, Bayer, Abbvie and Fractyl, and research sponsorship from Guerbet and the National Institutes of Health. Dr. Trolice had no financial conflicts to disclose and serves on the Editorial Advisory Board of Ob.Gyn News.

Approximately 3% of youth who tested positive for COVID-19 in an emergency department setting had severe outcomes after 2 weeks, but this risk was 0.5% among those not admitted to the hospital, based on data from more than 3,000 individuals aged 18 and younger.

In the early stages of the COVID-19 pandemic, youth younger than 18 years accounted for fewer than 5% of reported cases, but now account for approximately 25% of positive cases, wrote Anna L. Funk, PhD, of the University of Calgary, Alberta, Canada, and colleagues.

However, the risk of severe outcomes of youth with COVID-19 remains poorly understood and data from large studies are lacking, they noted.

In a prospective cohort study published in JAMA Network Open, the researchers reviewed data from 3,221 children and adolescents who were tested for COVID-19 at one of 41 emergency departments in 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States between March 2020 and June 2021. Positive infections were confirmed by polymerase chain reaction (PCR) testing. At 14 days’ follow-up after a positive test, 735 patients (22.8%), were hospitalized, 107 (3.3%) had severe outcomes, and 4 (0.12%) had died. Severe outcomes were significantly more likely in children aged 5-10 years and 10-18 years vs. less than 1 year (odds ratios, 1.60 and 2.39, respectively), and in children with a self-reported chronic illness (OR, 2.34) or a prior episode of pneumonia (OR, 3.15).

Severe outcomes were more likely in patients who presented with symptoms that started 4-7 days before seeking care, compared with those whose symptoms started 0-3 days before seeking care (OR, 2.22).

The researchers also reviewed data from a subgroup of 2,510 individuals who were discharged home from the ED after initial testing. At 14 days’ follow-up, 50 of these patients (2.0%) were hospitalized and 12 (0.5%) had severe outcomes. In addition, the researchers found that the risk of severe outcomes among hospitalized COVID-19–positive youth was nearly four times higher, compared with hospitalized youth who tested negative for COVID-19 (risk difference, 3.9%).

Previous retrospective studies of severe outcomes in children and adolescents with COVID-19 have yielded varying results, in part because of the variation in study populations, the researchers noted in their discussion of the findings. “Our study population provides a risk estimate for youths brought for ED care.” Therefore, “Our lower estimate of severe disease likely reflects our stringent definition, which required the occurrence of complications or specific invasive interventions,” they said.

The study limitations included the potential overestimation of the risk of severe outcomes because patients were recruited in the ED, the researchers noted. Other limitations included variation in regional case definitions, screening criteria, and testing capacity among different sites and time periods. “Thus, 5% of our SARS-CoV-2–positive participants were asymptomatic – most of whom were tested as they were positive contacts of known cases or as part of routine screening procedures,” they said. The findings also are not generalizable to all community EDs and did not account for variants, they added.

However, the results were strengthened by the ability to compare outcomes for children with positive tests to similar children with negative tests, and add to the literature showing an increased risk of severe outcomes for those hospitalized with positive tests, the researchers concluded.
 

Data may inform clinical decisions

“The data [in the current study] are concerning for severe outcomes for children even prior to the Omicron strain,” said Margaret Thew, DNP, FP-BC, of Children’s Wisconsin-Milwaukee Hospital, in an interview. “Presently, the number of children infected with the Omicron strain is much higher and hospitalizations among children are at their highest since COVID-19 began,” she said. “For medical providers caring for this population, the study sheds light on pediatric patients who may be at higher risk of severe illness when they become infected with COVID-19,” she added.

“I was surprised by how high the number of pediatric patients hospitalized (22%) and the percentage (3%) with severe disease were during this time,” given that the timeline for these data preceded the spread of the Omicron strain, said Ms. Thew. “The risk of prior pneumonia was quite surprising. I do not recall seeing prior pneumonia as a risk factor for more severe COVID-19 with children or adults,” she added.

The take-home messaging for clinicians caring for children and adolescents is the added knowledge of the risk factors for severe outcomes from COVID-19, including the 10-18 age range, chronic illness, prior pneumonia, and longer symptom duration before seeking care in the ED, Ms. Thew emphasized.

However, additional research is needed on the impact of the new strains of COVID-19 on pediatric and adolescent hospitalizations, Ms. Thew said. Research also is needed on the other illnesses that have resulted from COVID-19, including illness requiring antibiotic use or medical interventions or treatments, and on the risk of combined COVID-19 and influenza viruses, she noted.

The study was supported by the Canadian Institutes of Health Research, Alberta Innovates, the Alberta Health Services University of Calgary Clinical Research Fund, the Alberta Children’s Hospital Research Institute, the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis, and the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine Small Grants Program. Lead author Dr. Funk was supported by the University of Calgary Eyes-High Post-Doctoral Research Fund, but had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.

Approximately 3% of youth who tested positive for COVID-19 in an emergency department setting had severe outcomes after 2 weeks, but this risk was 0.5% among those not admitted to the hospital, based on data from more than 3,000 individuals aged 18 and younger.

In the early stages of the COVID-19 pandemic, youth younger than 18 years accounted for fewer than 5% of reported cases, but now account for approximately 25% of positive cases, wrote Anna L. Funk, PhD, of the University of Calgary, Alberta, Canada, and colleagues.

However, the risk of severe outcomes of youth with COVID-19 remains poorly understood and data from large studies are lacking, they noted.

In a prospective cohort study published in JAMA Network Open, the researchers reviewed data from 3,221 children and adolescents who were tested for COVID-19 at one of 41 emergency departments in 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States between March 2020 and June 2021. Positive infections were confirmed by polymerase chain reaction (PCR) testing. At 14 days’ follow-up after a positive test, 735 patients (22.8%), were hospitalized, 107 (3.3%) had severe outcomes, and 4 (0.12%) had died. Severe outcomes were significantly more likely in children aged 5-10 years and 10-18 years vs. less than 1 year (odds ratios, 1.60 and 2.39, respectively), and in children with a self-reported chronic illness (OR, 2.34) or a prior episode of pneumonia (OR, 3.15).

Severe outcomes were more likely in patients who presented with symptoms that started 4-7 days before seeking care, compared with those whose symptoms started 0-3 days before seeking care (OR, 2.22).

The researchers also reviewed data from a subgroup of 2,510 individuals who were discharged home from the ED after initial testing. At 14 days’ follow-up, 50 of these patients (2.0%) were hospitalized and 12 (0.5%) had severe outcomes. In addition, the researchers found that the risk of severe outcomes among hospitalized COVID-19–positive youth was nearly four times higher, compared with hospitalized youth who tested negative for COVID-19 (risk difference, 3.9%).

Previous retrospective studies of severe outcomes in children and adolescents with COVID-19 have yielded varying results, in part because of the variation in study populations, the researchers noted in their discussion of the findings. “Our study population provides a risk estimate for youths brought for ED care.” Therefore, “Our lower estimate of severe disease likely reflects our stringent definition, which required the occurrence of complications or specific invasive interventions,” they said.

The study limitations included the potential overestimation of the risk of severe outcomes because patients were recruited in the ED, the researchers noted. Other limitations included variation in regional case definitions, screening criteria, and testing capacity among different sites and time periods. “Thus, 5% of our SARS-CoV-2–positive participants were asymptomatic – most of whom were tested as they were positive contacts of known cases or as part of routine screening procedures,” they said. The findings also are not generalizable to all community EDs and did not account for variants, they added.

However, the results were strengthened by the ability to compare outcomes for children with positive tests to similar children with negative tests, and add to the literature showing an increased risk of severe outcomes for those hospitalized with positive tests, the researchers concluded.
 

Data may inform clinical decisions

“The data [in the current study] are concerning for severe outcomes for children even prior to the Omicron strain,” said Margaret Thew, DNP, FP-BC, of Children’s Wisconsin-Milwaukee Hospital, in an interview. “Presently, the number of children infected with the Omicron strain is much higher and hospitalizations among children are at their highest since COVID-19 began,” she said. “For medical providers caring for this population, the study sheds light on pediatric patients who may be at higher risk of severe illness when they become infected with COVID-19,” she added.

“I was surprised by how high the number of pediatric patients hospitalized (22%) and the percentage (3%) with severe disease were during this time,” given that the timeline for these data preceded the spread of the Omicron strain, said Ms. Thew. “The risk of prior pneumonia was quite surprising. I do not recall seeing prior pneumonia as a risk factor for more severe COVID-19 with children or adults,” she added.

The take-home messaging for clinicians caring for children and adolescents is the added knowledge of the risk factors for severe outcomes from COVID-19, including the 10-18 age range, chronic illness, prior pneumonia, and longer symptom duration before seeking care in the ED, Ms. Thew emphasized.

However, additional research is needed on the impact of the new strains of COVID-19 on pediatric and adolescent hospitalizations, Ms. Thew said. Research also is needed on the other illnesses that have resulted from COVID-19, including illness requiring antibiotic use or medical interventions or treatments, and on the risk of combined COVID-19 and influenza viruses, she noted.

The study was supported by the Canadian Institutes of Health Research, Alberta Innovates, the Alberta Health Services University of Calgary Clinical Research Fund, the Alberta Children’s Hospital Research Institute, the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis, and the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine Small Grants Program. Lead author Dr. Funk was supported by the University of Calgary Eyes-High Post-Doctoral Research Fund, but had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.

Approximately 3% of youth who tested positive for COVID-19 in an emergency department setting had severe outcomes after 2 weeks, but this risk was 0.5% among those not admitted to the hospital, based on data from more than 3,000 individuals aged 18 and younger.

In the early stages of the COVID-19 pandemic, youth younger than 18 years accounted for fewer than 5% of reported cases, but now account for approximately 25% of positive cases, wrote Anna L. Funk, PhD, of the University of Calgary, Alberta, Canada, and colleagues.

However, the risk of severe outcomes of youth with COVID-19 remains poorly understood and data from large studies are lacking, they noted.

In a prospective cohort study published in JAMA Network Open, the researchers reviewed data from 3,221 children and adolescents who were tested for COVID-19 at one of 41 emergency departments in 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States between March 2020 and June 2021. Positive infections were confirmed by polymerase chain reaction (PCR) testing. At 14 days’ follow-up after a positive test, 735 patients (22.8%), were hospitalized, 107 (3.3%) had severe outcomes, and 4 (0.12%) had died. Severe outcomes were significantly more likely in children aged 5-10 years and 10-18 years vs. less than 1 year (odds ratios, 1.60 and 2.39, respectively), and in children with a self-reported chronic illness (OR, 2.34) or a prior episode of pneumonia (OR, 3.15).

Severe outcomes were more likely in patients who presented with symptoms that started 4-7 days before seeking care, compared with those whose symptoms started 0-3 days before seeking care (OR, 2.22).

The researchers also reviewed data from a subgroup of 2,510 individuals who were discharged home from the ED after initial testing. At 14 days’ follow-up, 50 of these patients (2.0%) were hospitalized and 12 (0.5%) had severe outcomes. In addition, the researchers found that the risk of severe outcomes among hospitalized COVID-19–positive youth was nearly four times higher, compared with hospitalized youth who tested negative for COVID-19 (risk difference, 3.9%).

Previous retrospective studies of severe outcomes in children and adolescents with COVID-19 have yielded varying results, in part because of the variation in study populations, the researchers noted in their discussion of the findings. “Our study population provides a risk estimate for youths brought for ED care.” Therefore, “Our lower estimate of severe disease likely reflects our stringent definition, which required the occurrence of complications or specific invasive interventions,” they said.

The study limitations included the potential overestimation of the risk of severe outcomes because patients were recruited in the ED, the researchers noted. Other limitations included variation in regional case definitions, screening criteria, and testing capacity among different sites and time periods. “Thus, 5% of our SARS-CoV-2–positive participants were asymptomatic – most of whom were tested as they were positive contacts of known cases or as part of routine screening procedures,” they said. The findings also are not generalizable to all community EDs and did not account for variants, they added.

However, the results were strengthened by the ability to compare outcomes for children with positive tests to similar children with negative tests, and add to the literature showing an increased risk of severe outcomes for those hospitalized with positive tests, the researchers concluded.
 

Data may inform clinical decisions

“The data [in the current study] are concerning for severe outcomes for children even prior to the Omicron strain,” said Margaret Thew, DNP, FP-BC, of Children’s Wisconsin-Milwaukee Hospital, in an interview. “Presently, the number of children infected with the Omicron strain is much higher and hospitalizations among children are at their highest since COVID-19 began,” she said. “For medical providers caring for this population, the study sheds light on pediatric patients who may be at higher risk of severe illness when they become infected with COVID-19,” she added.

“I was surprised by how high the number of pediatric patients hospitalized (22%) and the percentage (3%) with severe disease were during this time,” given that the timeline for these data preceded the spread of the Omicron strain, said Ms. Thew. “The risk of prior pneumonia was quite surprising. I do not recall seeing prior pneumonia as a risk factor for more severe COVID-19 with children or adults,” she added.

The take-home messaging for clinicians caring for children and adolescents is the added knowledge of the risk factors for severe outcomes from COVID-19, including the 10-18 age range, chronic illness, prior pneumonia, and longer symptom duration before seeking care in the ED, Ms. Thew emphasized.

However, additional research is needed on the impact of the new strains of COVID-19 on pediatric and adolescent hospitalizations, Ms. Thew said. Research also is needed on the other illnesses that have resulted from COVID-19, including illness requiring antibiotic use or medical interventions or treatments, and on the risk of combined COVID-19 and influenza viruses, she noted.

The study was supported by the Canadian Institutes of Health Research, Alberta Innovates, the Alberta Health Services University of Calgary Clinical Research Fund, the Alberta Children’s Hospital Research Institute, the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis, and the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine Small Grants Program. Lead author Dr. Funk was supported by the University of Calgary Eyes-High Post-Doctoral Research Fund, but had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.