Federal Practitioner

Key clinical point: Compared with sorafenib, atezolizumab-bevacizumab led to more frequent acute variceal bleeding (AVB) in patients with locally advanced hepatocellular carcinoma (HCC) and cirrhosis, with a history of AVB being associated with AVB during follow-up.

Major finding: At 1 year, patients who received atezolizumab-bevacizumab vs sorafenib had significantly higher AVB occurrence (21% vs 5%; P = .02). A previous history of AVB was independently associated with AVB during therapy (adjusted hazard ratio 10.58; P = .03).

Study details: This single-center prospective study included 43 patients with locally advanced HCC and cirrhosis who received atezolizumab-bevacizumab and a retrospective series of 122 control patients who received sorafenib.

Disclosures: This study did not receive any funding. No information on conflicts of interest was provided.

Source: Larrey E et al. A history of variceal bleeding is associated with further bleeding under atezolizumab-bevacizumab in patients with HCC. Liver Int. 2022 (Oct 18). Doi: 10.1111/liv.15458

Key clinical point: Compared with sorafenib, atezolizumab-bevacizumab led to more frequent acute variceal bleeding (AVB) in patients with locally advanced hepatocellular carcinoma (HCC) and cirrhosis, with a history of AVB being associated with AVB during follow-up.

Major finding: At 1 year, patients who received atezolizumab-bevacizumab vs sorafenib had significantly higher AVB occurrence (21% vs 5%; P = .02). A previous history of AVB was independently associated with AVB during therapy (adjusted hazard ratio 10.58; P = .03).

Study details: This single-center prospective study included 43 patients with locally advanced HCC and cirrhosis who received atezolizumab-bevacizumab and a retrospective series of 122 control patients who received sorafenib.

Disclosures: This study did not receive any funding. No information on conflicts of interest was provided.

Source: Larrey E et al. A history of variceal bleeding is associated with further bleeding under atezolizumab-bevacizumab in patients with HCC. Liver Int. 2022 (Oct 18). Doi: 10.1111/liv.15458

Key clinical point: Compared with sorafenib, atezolizumab-bevacizumab led to more frequent acute variceal bleeding (AVB) in patients with locally advanced hepatocellular carcinoma (HCC) and cirrhosis, with a history of AVB being associated with AVB during follow-up.

Major finding: At 1 year, patients who received atezolizumab-bevacizumab vs sorafenib had significantly higher AVB occurrence (21% vs 5%; P = .02). A previous history of AVB was independently associated with AVB during therapy (adjusted hazard ratio 10.58; P = .03).

Study details: This single-center prospective study included 43 patients with locally advanced HCC and cirrhosis who received atezolizumab-bevacizumab and a retrospective series of 122 control patients who received sorafenib.

Disclosures: This study did not receive any funding. No information on conflicts of interest was provided.

Source: Larrey E et al. A history of variceal bleeding is associated with further bleeding under atezolizumab-bevacizumab in patients with HCC. Liver Int. 2022 (Oct 18). Doi: 10.1111/liv.15458

Key clinical point: Highly elevated antidrug antibody (ADA) levels (≥1,000 ng/mL) at 3 weeks (cycle 2 day 1 [C2D1]) may be associated with poor clinical outcomes after atezolizumab/bevacizumab (Atezo/Bev) treatment in patients with advanced hepatocellular carcinoma (HCC).

Major finding: In both discovery cohort (DC) and validation cohort (VC), patients with high vs low ADA levels at C2D1 had worse progression-free survival (DC: hazard ratio [HR] 2.84; P = .005; VC: HR 2.52; P = .006) and overall survival (DC: HR 3.30; P = .003; VC: HR 5.81; P = .001).

Study details: This prospective cohort study included 132 patients with advanced HCC treated with first-line Atezo/Bev (DC n = 50; VC n = 82).

Disclosures: This study was sponsored by a National Research Foundation of Korea grant funded by the Korean government and others. Some authors reported serving as advisors for or receiving personal fees or grants from various sources. Two authors declared having a pending method patent for predicting therapeutic response to biologic drugs by quantifying blood ADA.

Source: Kim C et al. Association of high levels of antidrug antibodies against atezolizumab with clinical outcomes and T-cell responses in patients with hepatocellular carcinoma. JAMA Oncol. 2022 (Oct 20). Doi: 10.1001/jamaoncol.2022.4733

Key clinical point: Highly elevated antidrug antibody (ADA) levels (≥1,000 ng/mL) at 3 weeks (cycle 2 day 1 [C2D1]) may be associated with poor clinical outcomes after atezolizumab/bevacizumab (Atezo/Bev) treatment in patients with advanced hepatocellular carcinoma (HCC).

Major finding: In both discovery cohort (DC) and validation cohort (VC), patients with high vs low ADA levels at C2D1 had worse progression-free survival (DC: hazard ratio [HR] 2.84; P = .005; VC: HR 2.52; P = .006) and overall survival (DC: HR 3.30; P = .003; VC: HR 5.81; P = .001).

Study details: This prospective cohort study included 132 patients with advanced HCC treated with first-line Atezo/Bev (DC n = 50; VC n = 82).

Disclosures: This study was sponsored by a National Research Foundation of Korea grant funded by the Korean government and others. Some authors reported serving as advisors for or receiving personal fees or grants from various sources. Two authors declared having a pending method patent for predicting therapeutic response to biologic drugs by quantifying blood ADA.

Source: Kim C et al. Association of high levels of antidrug antibodies against atezolizumab with clinical outcomes and T-cell responses in patients with hepatocellular carcinoma. JAMA Oncol. 2022 (Oct 20). Doi: 10.1001/jamaoncol.2022.4733

Key clinical point: Highly elevated antidrug antibody (ADA) levels (≥1,000 ng/mL) at 3 weeks (cycle 2 day 1 [C2D1]) may be associated with poor clinical outcomes after atezolizumab/bevacizumab (Atezo/Bev) treatment in patients with advanced hepatocellular carcinoma (HCC).

Major finding: In both discovery cohort (DC) and validation cohort (VC), patients with high vs low ADA levels at C2D1 had worse progression-free survival (DC: hazard ratio [HR] 2.84; P = .005; VC: HR 2.52; P = .006) and overall survival (DC: HR 3.30; P = .003; VC: HR 5.81; P = .001).

Study details: This prospective cohort study included 132 patients with advanced HCC treated with first-line Atezo/Bev (DC n = 50; VC n = 82).

Disclosures: This study was sponsored by a National Research Foundation of Korea grant funded by the Korean government and others. Some authors reported serving as advisors for or receiving personal fees or grants from various sources. Two authors declared having a pending method patent for predicting therapeutic response to biologic drugs by quantifying blood ADA.

Source: Kim C et al. Association of high levels of antidrug antibodies against atezolizumab with clinical outcomes and T-cell responses in patients with hepatocellular carcinoma. JAMA Oncol. 2022 (Oct 20). Doi: 10.1001/jamaoncol.2022.4733

Higher levels of exposure to outdoor artificial light at night are significantly linked with markers of diabetes and impaired glucose homeostasis, in a new national, cross-sectional study from China.

The results showed a 7% significant increase in diabetes prevalence per quintile exposure to artificial light at night (prevalence ratio, 1.07), report Ruizhi Zheng, PhD, of the Shanghai (China) Jiaotong University School of Medicine, and colleagues. People living in areas with the most exposure to light at night had a 28% higher prevalence of diabetes than those living in places with the lowest exposure (PR, 1.28), the researchers found.

The study was published online  in Diabetologia.

Previous animal studies have shown that exposure to light at night may interfere with circadian rhythms and affect glucose homeostasis, the study team note. Other research has demonstrated that chronic exposure to moderate indoor light during sleep elevated the prevalence of diabetes in older adults, compared with those sleeping in a dim setting, the authors add.

“Our findings contribute to the growing literature suggesting that artificial light at night is detrimental to health and demonstrate that artificial light at night may be a potential novel risk factor for diabetes,” they write.

“Considering the coexistence of the diabetes epidemic and the widespread influence of light pollution at night, the positive associations indicate an urgent need for countries and governments to develop effective prevention and intervention policies and to protect people from the adverse health effects of light pollution at night,” the study authors stress.

Gareth Nye, PhD, senior lecturer at the University of Chester, England, agreed that prior research has found an association between metabolic conditions, such as diabetes, and artificial light at night, with most theories as to the cause focusing on the body’s natural circadian cycle.

He said that internal clocks regulate a variety of bodily processes, such as metabolism and hormone synthesis. They also affect sleep patterns by interfering with synthesis of the hormone melatonin, which is essential for sound sleep, Dr. Nye told the UK Science Media Centre.

However, he stressed that much more research is needed before any link can be considered definitive.
 

Outdoor night light exposure linked to fasting glucose, A1c

The Chinese researchers set out to approximate the relationships between diabetes prevalence and glucose homeostasis with chronic exposure to outdoor light at night. 

They assessed 98,658 participants from the China Noncommunicable Disease Surveillance Study across 162 sites. The mean age of participants was 42.7 years. Female participants comprised 49.2% of the study cohort.

Diabetes was defined based on American Diabetes Association criteria. Satellite data were used to determine exposure to outdoor light at night in 2010. The associations between light exposure at night and indicators of glucose homeostasis were investigated.

Prevalence ratios were calculated and adjusted for sex, age, smoking status, education, body mass index, physical activity, household income, family history of diabetes, rural/urban areas, drinking status, and use of lipid-lowering prescription drugs (primarily statins) or antihypertensives.

The findings showed exposure levels to outdoor light at night were positively linked with 2-hour and fasting glucose concentrations, A1c, and insulin resistance (measured using homeostatic model assessment [HOMA]), but negatively related to β-cell function (measured using HOMA).
 

More research needed

“We advise caution against causal interpretation of the findings and call for further studies involving direct measurement of individual exposure to light at night,” the researchers conclude.

Dr. Nye agreed.

“One issue with this study is that the areas with the highest outdoor artificial light levels are likely to be those in urban areas and bigger cities. It has been known for a long time now that living in an urbanized area increases your risk of obesity through increased access to high-fat and convenience food, less physical activity levels due to transport links, and less social activities. The authors also state this and the fact participants tended to be older,” he noted.

Large datasets are used in this investigation, however, which generally increases the reliability of the data, he observed.

But it is also “unclear as to whether the population here was selected for this study or was retrospectively analyzed, which poses reliability issues, as does the selection of the representative sample, as it is not discussed,” he noted.

Ultimately, there is no confirmed evidence of the link, and until further work is done to directly link light exposure and diabetes in humans, “the link will remain an association only,” he concluded.

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

Higher levels of exposure to outdoor artificial light at night are significantly linked with markers of diabetes and impaired glucose homeostasis, in a new national, cross-sectional study from China.

The results showed a 7% significant increase in diabetes prevalence per quintile exposure to artificial light at night (prevalence ratio, 1.07), report Ruizhi Zheng, PhD, of the Shanghai (China) Jiaotong University School of Medicine, and colleagues. People living in areas with the most exposure to light at night had a 28% higher prevalence of diabetes than those living in places with the lowest exposure (PR, 1.28), the researchers found.

The study was published online  in Diabetologia.

Previous animal studies have shown that exposure to light at night may interfere with circadian rhythms and affect glucose homeostasis, the study team note. Other research has demonstrated that chronic exposure to moderate indoor light during sleep elevated the prevalence of diabetes in older adults, compared with those sleeping in a dim setting, the authors add.

“Our findings contribute to the growing literature suggesting that artificial light at night is detrimental to health and demonstrate that artificial light at night may be a potential novel risk factor for diabetes,” they write.

“Considering the coexistence of the diabetes epidemic and the widespread influence of light pollution at night, the positive associations indicate an urgent need for countries and governments to develop effective prevention and intervention policies and to protect people from the adverse health effects of light pollution at night,” the study authors stress.

Gareth Nye, PhD, senior lecturer at the University of Chester, England, agreed that prior research has found an association between metabolic conditions, such as diabetes, and artificial light at night, with most theories as to the cause focusing on the body’s natural circadian cycle.

He said that internal clocks regulate a variety of bodily processes, such as metabolism and hormone synthesis. They also affect sleep patterns by interfering with synthesis of the hormone melatonin, which is essential for sound sleep, Dr. Nye told the UK Science Media Centre.

However, he stressed that much more research is needed before any link can be considered definitive.
 

Outdoor night light exposure linked to fasting glucose, A1c

The Chinese researchers set out to approximate the relationships between diabetes prevalence and glucose homeostasis with chronic exposure to outdoor light at night. 

They assessed 98,658 participants from the China Noncommunicable Disease Surveillance Study across 162 sites. The mean age of participants was 42.7 years. Female participants comprised 49.2% of the study cohort.

Diabetes was defined based on American Diabetes Association criteria. Satellite data were used to determine exposure to outdoor light at night in 2010. The associations between light exposure at night and indicators of glucose homeostasis were investigated.

Prevalence ratios were calculated and adjusted for sex, age, smoking status, education, body mass index, physical activity, household income, family history of diabetes, rural/urban areas, drinking status, and use of lipid-lowering prescription drugs (primarily statins) or antihypertensives.

The findings showed exposure levels to outdoor light at night were positively linked with 2-hour and fasting glucose concentrations, A1c, and insulin resistance (measured using homeostatic model assessment [HOMA]), but negatively related to β-cell function (measured using HOMA).
 

More research needed

“We advise caution against causal interpretation of the findings and call for further studies involving direct measurement of individual exposure to light at night,” the researchers conclude.

Dr. Nye agreed.

“One issue with this study is that the areas with the highest outdoor artificial light levels are likely to be those in urban areas and bigger cities. It has been known for a long time now that living in an urbanized area increases your risk of obesity through increased access to high-fat and convenience food, less physical activity levels due to transport links, and less social activities. The authors also state this and the fact participants tended to be older,” he noted.

Large datasets are used in this investigation, however, which generally increases the reliability of the data, he observed.

But it is also “unclear as to whether the population here was selected for this study or was retrospectively analyzed, which poses reliability issues, as does the selection of the representative sample, as it is not discussed,” he noted.

Ultimately, there is no confirmed evidence of the link, and until further work is done to directly link light exposure and diabetes in humans, “the link will remain an association only,” he concluded.

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

Higher levels of exposure to outdoor artificial light at night are significantly linked with markers of diabetes and impaired glucose homeostasis, in a new national, cross-sectional study from China.

The results showed a 7% significant increase in diabetes prevalence per quintile exposure to artificial light at night (prevalence ratio, 1.07), report Ruizhi Zheng, PhD, of the Shanghai (China) Jiaotong University School of Medicine, and colleagues. People living in areas with the most exposure to light at night had a 28% higher prevalence of diabetes than those living in places with the lowest exposure (PR, 1.28), the researchers found.

The study was published online  in Diabetologia.

Previous animal studies have shown that exposure to light at night may interfere with circadian rhythms and affect glucose homeostasis, the study team note. Other research has demonstrated that chronic exposure to moderate indoor light during sleep elevated the prevalence of diabetes in older adults, compared with those sleeping in a dim setting, the authors add.

“Our findings contribute to the growing literature suggesting that artificial light at night is detrimental to health and demonstrate that artificial light at night may be a potential novel risk factor for diabetes,” they write.

“Considering the coexistence of the diabetes epidemic and the widespread influence of light pollution at night, the positive associations indicate an urgent need for countries and governments to develop effective prevention and intervention policies and to protect people from the adverse health effects of light pollution at night,” the study authors stress.

Gareth Nye, PhD, senior lecturer at the University of Chester, England, agreed that prior research has found an association between metabolic conditions, such as diabetes, and artificial light at night, with most theories as to the cause focusing on the body’s natural circadian cycle.

He said that internal clocks regulate a variety of bodily processes, such as metabolism and hormone synthesis. They also affect sleep patterns by interfering with synthesis of the hormone melatonin, which is essential for sound sleep, Dr. Nye told the UK Science Media Centre.

However, he stressed that much more research is needed before any link can be considered definitive.
 

Outdoor night light exposure linked to fasting glucose, A1c

The Chinese researchers set out to approximate the relationships between diabetes prevalence and glucose homeostasis with chronic exposure to outdoor light at night. 

They assessed 98,658 participants from the China Noncommunicable Disease Surveillance Study across 162 sites. The mean age of participants was 42.7 years. Female participants comprised 49.2% of the study cohort.

Diabetes was defined based on American Diabetes Association criteria. Satellite data were used to determine exposure to outdoor light at night in 2010. The associations between light exposure at night and indicators of glucose homeostasis were investigated.

Prevalence ratios were calculated and adjusted for sex, age, smoking status, education, body mass index, physical activity, household income, family history of diabetes, rural/urban areas, drinking status, and use of lipid-lowering prescription drugs (primarily statins) or antihypertensives.

The findings showed exposure levels to outdoor light at night were positively linked with 2-hour and fasting glucose concentrations, A1c, and insulin resistance (measured using homeostatic model assessment [HOMA]), but negatively related to β-cell function (measured using HOMA).
 

More research needed

“We advise caution against causal interpretation of the findings and call for further studies involving direct measurement of individual exposure to light at night,” the researchers conclude.

Dr. Nye agreed.

“One issue with this study is that the areas with the highest outdoor artificial light levels are likely to be those in urban areas and bigger cities. It has been known for a long time now that living in an urbanized area increases your risk of obesity through increased access to high-fat and convenience food, less physical activity levels due to transport links, and less social activities. The authors also state this and the fact participants tended to be older,” he noted.

Large datasets are used in this investigation, however, which generally increases the reliability of the data, he observed.

But it is also “unclear as to whether the population here was selected for this study or was retrospectively analyzed, which poses reliability issues, as does the selection of the representative sample, as it is not discussed,” he noted.

Ultimately, there is no confirmed evidence of the link, and until further work is done to directly link light exposure and diabetes in humans, “the link will remain an association only,” he concluded.

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

U.K. researchers have established that hypertension is associated with a 22% greater risk of severe COVID-19, with the odds of severe COVID-19 unaffected by medication type.

Hypertension “appears to be one of the commonest comorbidities in COVID-19 patients”, explained the authors of a new study, published in PLOS ONE. The authors highlighted that previous research had shown that hypertension was more prevalent in severe and fatal cases compared with all cases of COVID-19.

They pointed out, however, that whether hypertensive individuals have a higher risk of severe COVID-19, compared with nonhypertensives, and whether the absolute level of systolic blood pressure or the type of antihypertensive medication is related to this risk, remained “unclear.”

To try to answer these questions, the research team, led by University of Cambridge researchers, analyzed data from 16,134 individuals who tested positive for COVID-19 (mean age 65.3 years, 47% male, 90% white), 40% were diagnosed with essential hypertension at the analysis baseline – 22% of whom had developed severe COVID-19.

Systolic blood pressure (SBP) was categorized by 10–mm Hg ranges, starting from < 120 mm Hg up to 180+ mm Hg, with the reference category defined as 120-129 mm Hg, based on data from the SPRINT study, which demonstrated that intensive SBP lowering to below 120 mm Hg, as compared with the traditional threshold of 140 mm Hg, was beneficial. Diastolic blood pressure was categorized by 10–mm Hg ranges, starting from < 60 mm Hg up to 100+ mm Hg with 80-90 mm Hg being the reference category.

In their analyses the researchers adjusted for age, sex, body mass index, ethnicity, smoking status, diabetes status, socioeconomic status, and inflammation (C-reactive protein [CRP]), as these were proposed as potential confounders. To assess the direct effect of hypertension on COVID-19, they also adjusted for intermediate variables, including cardiovascular comorbidities and stroke, on the causal pathway between hypertension and severe COVID-19.
 

Majority of effect of hypertension on severe COVID-19 was direct

The unadjusted odds ratio of the association between hypertension and severe COVID-19 was 2.33 (95% confidence interval, 2.16-2.51), the authors emphasized. They found that, after adjusting for all confounding variables, hypertension was associated with 22% higher odds of severe COVID-19 (OR, 1.22; 95% CI, 1.12-1.33), compared with normotension.

Individuals with severe COVID-19 were marginally older, more likely to be male, and more deprived, the authors said. “They were also more likely to be hypertensive, compared with individuals without severe COVID-19, and a greater proportion of individuals with severe COVID-19 had cardiovascular comorbidities.”

The majority of the effect of hypertension on development of severe COVID-19 was “direct,” they said. However, a modest proportion of the effect was mediated via cardiovascular comorbidities such as peripheral vascular disease, MI, coronary heart disease, arrhythmias, and stroke. Of note, those with a history of stroke had a 47% higher risk of severe COVID-19 and those with a history of other cardiovascular comorbidities had a 30% higher risk of severe COVID-19, the authors commented.
 

J-shaped relationship

Of the total of 6,517 (40%) individuals who had a diagnosis of essential hypertension at baseline, 67% were treated (41% with monotherapy, 59% with combination therapy), and 33% were untreated.

There were similar numbers of severe COVID-19 in each medication group: ACE inhibitors, 34%; angiotensin receptor blockers (ARBs), 36%; and “other” medications 34%.

In hypertensive individuals receiving antihypertensive medications, there was a “J-shaped relationship” between the level of blood pressure and risk of severe COVID-19 when using a systolic blood pressure level of 120-129 mm Hg as a reference – 150-159 mm Hg versus 120-129 mm Hg (OR 1.91; 95% CI, 1.44-2.53), > 180+ mm Hg versus 120-129 mm Hg (OR 1.93; 95% CI, 1.06-3.51).

The authors commented that there was no evidence of a higher risk of severe COVID-19 until systolic blood pressure “exceeded 150 mm Hg.”

They said it was an interesting finding that “very well-controlled” systolic blood pressure < 120 mm Hg was associated with a 40% (OR, 1.40; 95% CI, 1.11-1.78) greater odds of severe COVID-19. “This may be due to reverse causality, where low systolic blood pressure levels may indicate poorer health, such that the occurrence of severe COVID-19 may be related to underlying disease rather than the level of SBP per se,” they suggested.

The J-shaped association observed remained after multiple adjustments, including presence of known cardiovascular comorbidities, which suggested a possible “real effect” of low SBP on severe COVID-19, “at least in treated hypertensive individuals.”

Their analyses also identified that, compared with a “normal” diastolic blood pressure (80-90 mm Hg), having a diastolic blood pressure higher than 90 mm Hg was associated with higher odds of severe COVID-19.

The association between hypertension and COVID-19 was “amplified” if the individuals were treated and their BP remained uncontrolled, the authors pointed out.

There did not appear to be any difference in the risk of severe COVID-19 between individuals taking ACE inhibitors and those taking ARBs or other antihypertensive medications, the authors said.
 

Better understanding of underlying mechanisms needed

Individuals with hypertension who tested positive for COVID-19 had “over twice” the risk of developing severe COVID-19, compared with nonhypertensive individuals, the authors said.

They highlighted that their findings also suggest that there are “further effects” influencing the severity of COVID-19 beyond a “dichotomous” diagnosis of hypertension.

“Individuals with a higher-than-target systolic blood pressure may be less healthy, less active, suffering more severe hypertension, or have developed drug-resistant hypertension, all suggesting that the effects of hypertension have already had detrimental physiological effects on the cardiovascular system, which in turn may offer some explanation for the higher risk of severe COVID-19 with uncontrolled SBP,” they explained.

“Hypertension is an important risk factor for COVID-19,” reiterated the authors, who emphasized that a better understanding of the underlying mechanisms driving this increased risk is warranted in case of “more severe strains or other viruses” in the future.

The authors have declared no competing interests.

A version of this article first appeared on Medscape UK.

U.K. researchers have established that hypertension is associated with a 22% greater risk of severe COVID-19, with the odds of severe COVID-19 unaffected by medication type.

Hypertension “appears to be one of the commonest comorbidities in COVID-19 patients”, explained the authors of a new study, published in PLOS ONE. The authors highlighted that previous research had shown that hypertension was more prevalent in severe and fatal cases compared with all cases of COVID-19.

They pointed out, however, that whether hypertensive individuals have a higher risk of severe COVID-19, compared with nonhypertensives, and whether the absolute level of systolic blood pressure or the type of antihypertensive medication is related to this risk, remained “unclear.”

To try to answer these questions, the research team, led by University of Cambridge researchers, analyzed data from 16,134 individuals who tested positive for COVID-19 (mean age 65.3 years, 47% male, 90% white), 40% were diagnosed with essential hypertension at the analysis baseline – 22% of whom had developed severe COVID-19.

Systolic blood pressure (SBP) was categorized by 10–mm Hg ranges, starting from < 120 mm Hg up to 180+ mm Hg, with the reference category defined as 120-129 mm Hg, based on data from the SPRINT study, which demonstrated that intensive SBP lowering to below 120 mm Hg, as compared with the traditional threshold of 140 mm Hg, was beneficial. Diastolic blood pressure was categorized by 10–mm Hg ranges, starting from < 60 mm Hg up to 100+ mm Hg with 80-90 mm Hg being the reference category.

In their analyses the researchers adjusted for age, sex, body mass index, ethnicity, smoking status, diabetes status, socioeconomic status, and inflammation (C-reactive protein [CRP]), as these were proposed as potential confounders. To assess the direct effect of hypertension on COVID-19, they also adjusted for intermediate variables, including cardiovascular comorbidities and stroke, on the causal pathway between hypertension and severe COVID-19.
 

Majority of effect of hypertension on severe COVID-19 was direct

The unadjusted odds ratio of the association between hypertension and severe COVID-19 was 2.33 (95% confidence interval, 2.16-2.51), the authors emphasized. They found that, after adjusting for all confounding variables, hypertension was associated with 22% higher odds of severe COVID-19 (OR, 1.22; 95% CI, 1.12-1.33), compared with normotension.

Individuals with severe COVID-19 were marginally older, more likely to be male, and more deprived, the authors said. “They were also more likely to be hypertensive, compared with individuals without severe COVID-19, and a greater proportion of individuals with severe COVID-19 had cardiovascular comorbidities.”

The majority of the effect of hypertension on development of severe COVID-19 was “direct,” they said. However, a modest proportion of the effect was mediated via cardiovascular comorbidities such as peripheral vascular disease, MI, coronary heart disease, arrhythmias, and stroke. Of note, those with a history of stroke had a 47% higher risk of severe COVID-19 and those with a history of other cardiovascular comorbidities had a 30% higher risk of severe COVID-19, the authors commented.
 

J-shaped relationship

Of the total of 6,517 (40%) individuals who had a diagnosis of essential hypertension at baseline, 67% were treated (41% with monotherapy, 59% with combination therapy), and 33% were untreated.

There were similar numbers of severe COVID-19 in each medication group: ACE inhibitors, 34%; angiotensin receptor blockers (ARBs), 36%; and “other” medications 34%.

In hypertensive individuals receiving antihypertensive medications, there was a “J-shaped relationship” between the level of blood pressure and risk of severe COVID-19 when using a systolic blood pressure level of 120-129 mm Hg as a reference – 150-159 mm Hg versus 120-129 mm Hg (OR 1.91; 95% CI, 1.44-2.53), > 180+ mm Hg versus 120-129 mm Hg (OR 1.93; 95% CI, 1.06-3.51).

The authors commented that there was no evidence of a higher risk of severe COVID-19 until systolic blood pressure “exceeded 150 mm Hg.”

They said it was an interesting finding that “very well-controlled” systolic blood pressure < 120 mm Hg was associated with a 40% (OR, 1.40; 95% CI, 1.11-1.78) greater odds of severe COVID-19. “This may be due to reverse causality, where low systolic blood pressure levels may indicate poorer health, such that the occurrence of severe COVID-19 may be related to underlying disease rather than the level of SBP per se,” they suggested.

The J-shaped association observed remained after multiple adjustments, including presence of known cardiovascular comorbidities, which suggested a possible “real effect” of low SBP on severe COVID-19, “at least in treated hypertensive individuals.”

Their analyses also identified that, compared with a “normal” diastolic blood pressure (80-90 mm Hg), having a diastolic blood pressure higher than 90 mm Hg was associated with higher odds of severe COVID-19.

The association between hypertension and COVID-19 was “amplified” if the individuals were treated and their BP remained uncontrolled, the authors pointed out.

There did not appear to be any difference in the risk of severe COVID-19 between individuals taking ACE inhibitors and those taking ARBs or other antihypertensive medications, the authors said.
 

Better understanding of underlying mechanisms needed

Individuals with hypertension who tested positive for COVID-19 had “over twice” the risk of developing severe COVID-19, compared with nonhypertensive individuals, the authors said.

They highlighted that their findings also suggest that there are “further effects” influencing the severity of COVID-19 beyond a “dichotomous” diagnosis of hypertension.

“Individuals with a higher-than-target systolic blood pressure may be less healthy, less active, suffering more severe hypertension, or have developed drug-resistant hypertension, all suggesting that the effects of hypertension have already had detrimental physiological effects on the cardiovascular system, which in turn may offer some explanation for the higher risk of severe COVID-19 with uncontrolled SBP,” they explained.

“Hypertension is an important risk factor for COVID-19,” reiterated the authors, who emphasized that a better understanding of the underlying mechanisms driving this increased risk is warranted in case of “more severe strains or other viruses” in the future.

The authors have declared no competing interests.

A version of this article first appeared on Medscape UK.

U.K. researchers have established that hypertension is associated with a 22% greater risk of severe COVID-19, with the odds of severe COVID-19 unaffected by medication type.

Hypertension “appears to be one of the commonest comorbidities in COVID-19 patients”, explained the authors of a new study, published in PLOS ONE. The authors highlighted that previous research had shown that hypertension was more prevalent in severe and fatal cases compared with all cases of COVID-19.

They pointed out, however, that whether hypertensive individuals have a higher risk of severe COVID-19, compared with nonhypertensives, and whether the absolute level of systolic blood pressure or the type of antihypertensive medication is related to this risk, remained “unclear.”

To try to answer these questions, the research team, led by University of Cambridge researchers, analyzed data from 16,134 individuals who tested positive for COVID-19 (mean age 65.3 years, 47% male, 90% white), 40% were diagnosed with essential hypertension at the analysis baseline – 22% of whom had developed severe COVID-19.

Systolic blood pressure (SBP) was categorized by 10–mm Hg ranges, starting from < 120 mm Hg up to 180+ mm Hg, with the reference category defined as 120-129 mm Hg, based on data from the SPRINT study, which demonstrated that intensive SBP lowering to below 120 mm Hg, as compared with the traditional threshold of 140 mm Hg, was beneficial. Diastolic blood pressure was categorized by 10–mm Hg ranges, starting from < 60 mm Hg up to 100+ mm Hg with 80-90 mm Hg being the reference category.

In their analyses the researchers adjusted for age, sex, body mass index, ethnicity, smoking status, diabetes status, socioeconomic status, and inflammation (C-reactive protein [CRP]), as these were proposed as potential confounders. To assess the direct effect of hypertension on COVID-19, they also adjusted for intermediate variables, including cardiovascular comorbidities and stroke, on the causal pathway between hypertension and severe COVID-19.
 

Majority of effect of hypertension on severe COVID-19 was direct

The unadjusted odds ratio of the association between hypertension and severe COVID-19 was 2.33 (95% confidence interval, 2.16-2.51), the authors emphasized. They found that, after adjusting for all confounding variables, hypertension was associated with 22% higher odds of severe COVID-19 (OR, 1.22; 95% CI, 1.12-1.33), compared with normotension.

Individuals with severe COVID-19 were marginally older, more likely to be male, and more deprived, the authors said. “They were also more likely to be hypertensive, compared with individuals without severe COVID-19, and a greater proportion of individuals with severe COVID-19 had cardiovascular comorbidities.”

The majority of the effect of hypertension on development of severe COVID-19 was “direct,” they said. However, a modest proportion of the effect was mediated via cardiovascular comorbidities such as peripheral vascular disease, MI, coronary heart disease, arrhythmias, and stroke. Of note, those with a history of stroke had a 47% higher risk of severe COVID-19 and those with a history of other cardiovascular comorbidities had a 30% higher risk of severe COVID-19, the authors commented.
 

J-shaped relationship

Of the total of 6,517 (40%) individuals who had a diagnosis of essential hypertension at baseline, 67% were treated (41% with monotherapy, 59% with combination therapy), and 33% were untreated.

There were similar numbers of severe COVID-19 in each medication group: ACE inhibitors, 34%; angiotensin receptor blockers (ARBs), 36%; and “other” medications 34%.

In hypertensive individuals receiving antihypertensive medications, there was a “J-shaped relationship” between the level of blood pressure and risk of severe COVID-19 when using a systolic blood pressure level of 120-129 mm Hg as a reference – 150-159 mm Hg versus 120-129 mm Hg (OR 1.91; 95% CI, 1.44-2.53), > 180+ mm Hg versus 120-129 mm Hg (OR 1.93; 95% CI, 1.06-3.51).

The authors commented that there was no evidence of a higher risk of severe COVID-19 until systolic blood pressure “exceeded 150 mm Hg.”

They said it was an interesting finding that “very well-controlled” systolic blood pressure < 120 mm Hg was associated with a 40% (OR, 1.40; 95% CI, 1.11-1.78) greater odds of severe COVID-19. “This may be due to reverse causality, where low systolic blood pressure levels may indicate poorer health, such that the occurrence of severe COVID-19 may be related to underlying disease rather than the level of SBP per se,” they suggested.

The J-shaped association observed remained after multiple adjustments, including presence of known cardiovascular comorbidities, which suggested a possible “real effect” of low SBP on severe COVID-19, “at least in treated hypertensive individuals.”

Their analyses also identified that, compared with a “normal” diastolic blood pressure (80-90 mm Hg), having a diastolic blood pressure higher than 90 mm Hg was associated with higher odds of severe COVID-19.

The association between hypertension and COVID-19 was “amplified” if the individuals were treated and their BP remained uncontrolled, the authors pointed out.

There did not appear to be any difference in the risk of severe COVID-19 between individuals taking ACE inhibitors and those taking ARBs or other antihypertensive medications, the authors said.
 

Better understanding of underlying mechanisms needed

Individuals with hypertension who tested positive for COVID-19 had “over twice” the risk of developing severe COVID-19, compared with nonhypertensive individuals, the authors said.

They highlighted that their findings also suggest that there are “further effects” influencing the severity of COVID-19 beyond a “dichotomous” diagnosis of hypertension.

“Individuals with a higher-than-target systolic blood pressure may be less healthy, less active, suffering more severe hypertension, or have developed drug-resistant hypertension, all suggesting that the effects of hypertension have already had detrimental physiological effects on the cardiovascular system, which in turn may offer some explanation for the higher risk of severe COVID-19 with uncontrolled SBP,” they explained.

“Hypertension is an important risk factor for COVID-19,” reiterated the authors, who emphasized that a better understanding of the underlying mechanisms driving this increased risk is warranted in case of “more severe strains or other viruses” in the future.

The authors have declared no competing interests.

A version of this article first appeared on Medscape UK.

A new model for predicting breast cancer risk that is based on standard clinical measures could be used to develop personalized breast screening strategies that are more effective than the current “one size fits all” approach, say researchers.

“Several breast cancer risk prediction models have been created, but we believe this is one of the first models designed to guide breast screening strategies over a person’s lifetime using real data from a screening program,” said study author Javier Louro, PhD, Hospital del Mar Medical Research Institute, Barcelona, Spain.

“Our model might be considered a key for designing personalized screening aimed at reducing the harms and increasing the benefits of mammographic screening,” he said in a statement.

Someone with a low risk “might be offered screening with standard mammography every 3 or 4 years instead of 2 years,” Dr. Louro explained.

“Someone with medium risk might be offered screening with advanced 3D mammography every 3 years, while those at a high risk might be offered a new screening test with mammography or MRI every year.”

However, he cautioned that “all of these strategies are still theoretical and should be studied with regard to their effectiveness.”

Dr. Louro was talking about the new model at the 13th European Breast Cancer Conference.
 

Details of the new prediction model

To develop the new model, Louro and colleagues conducted a retrospective study of 57,411 women who underwent mammography in four counties in Norway between 2007 and 2019 as part of the BreastScreen Norway program, and followed them up to 2022.

The team gathered data on age, breast density, family history of breast cancer, body mass index, age at menarche, alcohol habit, exercise, pregnancy, hormone replacement therapy, and benign breast disease, and compared women with and those without a breast cancer diagnosis.

All of these 10 variables used were found to significantly explain part of the variability in the breast cancer risk.

Overall, the 4-year breast cancer risk predicted by the resulting model varied across the participants, from 0.22% to 7.43%, at a median of 1.10%.

Bootstrap resampling analysis revealed that the model overestimated the risk for breast cancer, at an expected-to-observed ratio of 1.10.

The largest effect on risk was from breast density on mammography. Women with dense breasts were at much higher risk: the adjusted hazard ratio was 1.71 for women with Volpara Density Grade 4 vs Grade 2 and was 1.37 when compared with Grade 3.

Exercise had a large impact on breast cancer risk, the researchers found. Women who exercised for 4 or more hours per week had an adjusted hazard ratio of 0.65 for breast cancer risk compared with women who never exercised. Although this effect of exercise reducing the risk for breast cancer is now widely known, it is not usually included in models that predict breast cancer risk, the team pointed out.

The team concluded that their prediction model could be used to personalize breast screening for women according to their risk assessment, although they acknowledge that more work is needed. This work is based on one screening program in one country, and similar studies in different settings are needed.

Reacting to the findings, Laura Biganzoli, MD, co-chair of the European Breast Cancer Conference and director of the Breast Centre at Santo Stefano Hospital, Prato, Italy, commented, “We know that breast screening programs are beneficial, but we also know that some people will experience potential harms caused by false-positives or overdiagnosis.”

“This research shows how we might be able to identify people with a high risk of breast cancer, but equally how we could identify those with a low risk. So it’s an important step toward personalized screening,” Dr. Biganzoli said.

This study was supported by a grant from Instituto de Salud Carlos III FEDER (grant PI/00047). No relevant financial relationships declared.

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

A new model for predicting breast cancer risk that is based on standard clinical measures could be used to develop personalized breast screening strategies that are more effective than the current “one size fits all” approach, say researchers.

“Several breast cancer risk prediction models have been created, but we believe this is one of the first models designed to guide breast screening strategies over a person’s lifetime using real data from a screening program,” said study author Javier Louro, PhD, Hospital del Mar Medical Research Institute, Barcelona, Spain.

“Our model might be considered a key for designing personalized screening aimed at reducing the harms and increasing the benefits of mammographic screening,” he said in a statement.

Someone with a low risk “might be offered screening with standard mammography every 3 or 4 years instead of 2 years,” Dr. Louro explained.

“Someone with medium risk might be offered screening with advanced 3D mammography every 3 years, while those at a high risk might be offered a new screening test with mammography or MRI every year.”

However, he cautioned that “all of these strategies are still theoretical and should be studied with regard to their effectiveness.”

Dr. Louro was talking about the new model at the 13th European Breast Cancer Conference.
 

Details of the new prediction model

To develop the new model, Louro and colleagues conducted a retrospective study of 57,411 women who underwent mammography in four counties in Norway between 2007 and 2019 as part of the BreastScreen Norway program, and followed them up to 2022.

The team gathered data on age, breast density, family history of breast cancer, body mass index, age at menarche, alcohol habit, exercise, pregnancy, hormone replacement therapy, and benign breast disease, and compared women with and those without a breast cancer diagnosis.

All of these 10 variables used were found to significantly explain part of the variability in the breast cancer risk.

Overall, the 4-year breast cancer risk predicted by the resulting model varied across the participants, from 0.22% to 7.43%, at a median of 1.10%.

Bootstrap resampling analysis revealed that the model overestimated the risk for breast cancer, at an expected-to-observed ratio of 1.10.

The largest effect on risk was from breast density on mammography. Women with dense breasts were at much higher risk: the adjusted hazard ratio was 1.71 for women with Volpara Density Grade 4 vs Grade 2 and was 1.37 when compared with Grade 3.

Exercise had a large impact on breast cancer risk, the researchers found. Women who exercised for 4 or more hours per week had an adjusted hazard ratio of 0.65 for breast cancer risk compared with women who never exercised. Although this effect of exercise reducing the risk for breast cancer is now widely known, it is not usually included in models that predict breast cancer risk, the team pointed out.

The team concluded that their prediction model could be used to personalize breast screening for women according to their risk assessment, although they acknowledge that more work is needed. This work is based on one screening program in one country, and similar studies in different settings are needed.

Reacting to the findings, Laura Biganzoli, MD, co-chair of the European Breast Cancer Conference and director of the Breast Centre at Santo Stefano Hospital, Prato, Italy, commented, “We know that breast screening programs are beneficial, but we also know that some people will experience potential harms caused by false-positives or overdiagnosis.”

“This research shows how we might be able to identify people with a high risk of breast cancer, but equally how we could identify those with a low risk. So it’s an important step toward personalized screening,” Dr. Biganzoli said.

This study was supported by a grant from Instituto de Salud Carlos III FEDER (grant PI/00047). No relevant financial relationships declared.

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

A new model for predicting breast cancer risk that is based on standard clinical measures could be used to develop personalized breast screening strategies that are more effective than the current “one size fits all” approach, say researchers.

“Several breast cancer risk prediction models have been created, but we believe this is one of the first models designed to guide breast screening strategies over a person’s lifetime using real data from a screening program,” said study author Javier Louro, PhD, Hospital del Mar Medical Research Institute, Barcelona, Spain.

“Our model might be considered a key for designing personalized screening aimed at reducing the harms and increasing the benefits of mammographic screening,” he said in a statement.

Someone with a low risk “might be offered screening with standard mammography every 3 or 4 years instead of 2 years,” Dr. Louro explained.

“Someone with medium risk might be offered screening with advanced 3D mammography every 3 years, while those at a high risk might be offered a new screening test with mammography or MRI every year.”

However, he cautioned that “all of these strategies are still theoretical and should be studied with regard to their effectiveness.”

Dr. Louro was talking about the new model at the 13th European Breast Cancer Conference.
 

Details of the new prediction model

To develop the new model, Louro and colleagues conducted a retrospective study of 57,411 women who underwent mammography in four counties in Norway between 2007 and 2019 as part of the BreastScreen Norway program, and followed them up to 2022.

The team gathered data on age, breast density, family history of breast cancer, body mass index, age at menarche, alcohol habit, exercise, pregnancy, hormone replacement therapy, and benign breast disease, and compared women with and those without a breast cancer diagnosis.

All of these 10 variables used were found to significantly explain part of the variability in the breast cancer risk.

Overall, the 4-year breast cancer risk predicted by the resulting model varied across the participants, from 0.22% to 7.43%, at a median of 1.10%.

Bootstrap resampling analysis revealed that the model overestimated the risk for breast cancer, at an expected-to-observed ratio of 1.10.

The largest effect on risk was from breast density on mammography. Women with dense breasts were at much higher risk: the adjusted hazard ratio was 1.71 for women with Volpara Density Grade 4 vs Grade 2 and was 1.37 when compared with Grade 3.

Exercise had a large impact on breast cancer risk, the researchers found. Women who exercised for 4 or more hours per week had an adjusted hazard ratio of 0.65 for breast cancer risk compared with women who never exercised. Although this effect of exercise reducing the risk for breast cancer is now widely known, it is not usually included in models that predict breast cancer risk, the team pointed out.

The team concluded that their prediction model could be used to personalize breast screening for women according to their risk assessment, although they acknowledge that more work is needed. This work is based on one screening program in one country, and similar studies in different settings are needed.

Reacting to the findings, Laura Biganzoli, MD, co-chair of the European Breast Cancer Conference and director of the Breast Centre at Santo Stefano Hospital, Prato, Italy, commented, “We know that breast screening programs are beneficial, but we also know that some people will experience potential harms caused by false-positives or overdiagnosis.”

“This research shows how we might be able to identify people with a high risk of breast cancer, but equally how we could identify those with a low risk. So it’s an important step toward personalized screening,” Dr. Biganzoli said.

This study was supported by a grant from Instituto de Salud Carlos III FEDER (grant PI/00047). No relevant financial relationships declared.

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

A woman who had breast cancer for 23 years, and who had gone through 12 different lines of therapy, has shown a dramatic response to a novel cancer vaccine in a clinical trial.

A recent 6-month follow-up showed no evidence of new or recurrent disease, and scans showed regression of a distant bulky left adrenal metastasis, as well as at other sites.

A small site of residual hypermetabolism remains in the sternum, but this is thought to be related to scar tissue.

The patient, Stephanie Gangi, told Medscape Medical News that, before she entered into the trial for the novel cancer vaccine, she was “mentally and physically exhausted.” She had benefited from being diagnosed with hormone-positive breast cancer just as its treatment was evolving and progressing, which meant that, every time a treatment failed, “there was the next thing to try, which was great and kept me going.”

“But I will admit that, by age 66, and more than 20 years of cancer treatments, I was exhausted.”

Ms. Gangi, a New York City-based poet, essayist, and fiction writer, said she was “cautiously optimistic” about the cancer vaccine, but the “overriding thought was I wanted to avoid chemotherapy.”

“I was not really signing on for great outcomes, I was signing on for something that might keep chemo at bay. The biggest impact so far for me has been that, for the first time in more than a decade, I am not on any medication. That’s really amazing…and that means no side effects,” she said.

Ms. Gangi stopped the vaccine treatment this past July, and just over 3 months later, she is still “wrapping her head around” the fact that her cancer has regressed. “I’ve had breast cancer a long time,” she said, “and you can’t just snap your fingers and be fine.”

Although the two scans that she has had since the trial ended have been “astonishing,” she underlined that this is not about a ‘cure,’ but rather “clearing tumors for the first time in many years.”

“Cancer is sneaky and sinister, and it figures out how to circumvent all kinds of treatments,” she said, adding nevertheless that she is “happy and hopeful, and my family is thrilled, of course.”

Ms. Gangi was classed as having had a partial response to the cancer vaccine, one of a few in a small phase 1/2 trial at the Icahn School of Medicine at Mount Sinai in New York. One other patient also had a partial response, and one patient had a complete response.

However, six patients have progressive disease, and one has stable disease.  

These results come from an interim analysis of 10 patients from the trial, and show a 30% response rate. They were presented at the recent annual meeting of the Society for Immunotherapy of Cancer.

The vaccine that was being tested combines local low-dose radiation, intramural Flt3L, which stimulates dendritic cells, and intravenous poly-ICLC, an immune stimulating factor, with the PD-1 inhibitor pembrolizumab (Keytruda).

The result is that, instead of making a vaccine in a laboratory and administering it, “we’re actually formulating it within the body,” lead author Thomas Marron, MD, PhD, professor of medicine (hematology and medical oncology) at Mount Sinai, said in an interview.

“What people don’t realize,” he said, is that bulky tumor sites contain “a lot of dead tumor, because they grow so fast and in a haphazard way.” This means that the immune system can be recruited to recognize the dead tumor and “gobble up the dead stuff that’s already there,” he added.

The hope is that the immune system will then kill not only “the tumor you are injecting into, but also tumors elsewhere in the body,” Dr. Marron said. “So you’re basically using your body’s own immune system and on and off switches to vaccinate the patient against their cancer.”

Another patient in the trial who had a complete response to the vaccine was William Morrison, with non-Hodgkin lymphoma (NHL).

Mr. Morrison was diagnosed in 2017, at which time he was enrolled onto a phase 1 trial of an earlier version of this novel vaccine treatment regimen. “Basically, they didn’t get the results they were hoping for, and I still had the lymphoma,” he said. In 2018, his indolent follicular lymphoma transformed into an aggressive diffuse large B-cell lymphoma, for which Mr. Morrison was given six cycles of chemotherapy. This put him into remission and cleared his lymphoma.

“But the remission lasted for maybe a little over a year,” he said.

The cancer came back, and at that point he was given the opportunity to enroll in the Mount Sinai trial. At the end of the treatment, “everything was clear.”

“I’ve been for PET scans every 6 months, and I just had a scan done the other week, and everything has been fine…I’ve been pretty excited. I was pretty lucky.”

“This recent one really has worked wonders,” he said, “When they gave me the good news the other day. I felt like a big weight had been lifted.”

Mr. Morrison also said that he did not experience any serious adverse events while being treated with the vaccine. “Other than a few minor things, I tolerated it pretty well,” he said.

In contrast, Ms. Gangi said she experienced “intense” flu-like symptoms that started in the first few days after the treatment and lasted for a couple of days.
 

Need to improve response rate

The current trial achieved responses in 30% of patients, which “is great, [but] we want to be at 100%,” said Dr. Marron.

“What we’re doing in the laboratory right now is using this as an opportunity to study what it is that’s special about those three people who responded and what’s not happening in the other seven people, and we have some initial data that we’re analyzing,” he said.

“We are seeing that the patients who responded have a much more robust response to the Ft3L in particular…and that could suggest that maybe we need a better Ft3L, or we could think about other ways to potentially manipulate this vaccine.

“Most of the patients who are referred to me are people who have run out of options…and that usually means they’ve had many different types of chemotherapy,” Dr. Marron commented. For example, Ms. Gangi had already been through 12 different chemotherapy regimens.

Chemotherapy suppresses the immune system, but it’s not only that — also having an effect are all the other treatments aimed at reducing nausea and allergic reactions to the anti-cancer therapy, Dr. Marron explained.

“By the time that I see a patient,” Dr. Marron said, “oftentimes their immune system is not optimal. So another way in which we would hope to see better responses is by moving this vaccine earlier in the treatment paradigm, and administering it to patients as their first or second treatment.”

Senior author Joshua Brody, MD, director of the Lymphoma Immunotherapy Program at Mount Sinai’s Tisch Cancer Institute, added that it “might be easy” to incorporate the vaccine into earlier lines of therapy.

He said in an interview that both immunotherapy and radiation therapy are “standard” treatments, and the key is “adding multiple ingredients together that don’t have cumulative toxicity.”

“You can’t just chemo one plus chemo two, because they have some of the same toxicities, but the delightful thing here is this therapy had been quite safe.

“So in theory it would be fairly easy to incorporate this into earlier lines of therapy, once we can get a bit more proof of principle,” Dr. Brody said.

Approached for comment, Ann W. Silk, MD, said that the results are “particularly impressive because we know anti-PD-1 plus radiation therapy does not work in hormone-positive breast cancer or lymphoma.”

Dr. Silk, an oncologist at the Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School in Boston, said in an interview that one advantage of this vaccine is that it “is not restricted to a certain number of antigens and does not rely on an algorithm.”

“I would love to see more data in hormone-positive metastatic breast cancer patients,” she added. “I would use this approach after the hormonal treatments stop working, but before chemotherapy.”

Dr. Silk also said that the safety profile “looks quite good, and I imagine this approach would result in a much better quality of life for patients as compared to chemotherapy.”
 

Details of the trial and results

The Mount Sinai researchers had previously developed a personalized genomic cancer vaccine, PGV-001, which showed promise in a phase 1 trial in 13 patients with solid tumors or multiple myeloma and a high risk of recurrence after surgery or autologous stem cell transplant.

Next, they worked to develop the concept further to turn the tumor into its own vaccine, which involved inducing anti-tumor responses in indolent NHL, which typically responds poorly to checkpoint blockade, by combining Ft3L, low-dose irradiation, and poly-ICLC.

The next phase 1 trial showed that this approach was feasible, but preclinical modeling suggested that the addition of PD-1 blockade could improve the cure rates. The researchers therefore conducted the current trial, recruiting 10 patients with indolent NHL, metastatic breast cancer, or head and neck squamous cell carcinoma (HNSCC).

Patients were given local radiation therapy on days 1 and 2, and intramural Ft3L to the same tumor on day 9, followed by eight intravenous injections of poly-ICLC over 6 weeks. On day 23, they received their first of eight doses of pembrolizumab.

Dr. Marron explained that the radiotherapy increases the amount of dead material for the immune system to work on by “killing some of the tumor cells,” adding: “We’re not trying to kill the whole tumor with the radiation…it just starts the process of releasing some more of that dead stuff.”

He explained that Ft3L is a human growth factor that simulates dendritic cells, “which I always say are the professor cells of the immune system,” as they tell the body “what’s good and what’s bad.”

The poly-ICLC is “basically like a fake virus,” Dr. Marron said, as it “turns on those immune cells that have taken up the tumor antigen in the neighborhood” of the tumor, so they “teach the immune system that there is something bad”.

Finally, the pembrolizumab is there to “take the foot off the brake of the immune system” and “grease the wheels a bit more,” he added, even though it does not work in all patients, or in all tumor types, including indolent NHL.

The trial was planned in two phases. In the first part, six patients were enrolled to assess the safety of the approach; the phase 2 stage of the trial followed a Simon’s Two-Stage design, with the aim of recruiting seven patients of each tumor type, followed by a further 12 patients if they showed a response.

The current interim analysis that was presented at the SITC meeting focused on the first 10 patients in the phase 2 part, who were enrolled between April 2019 and July 2022. This included six patients with metastatic breast cancer, three with indolent NHL, and one with HNSCC, all of whom completed their first disease response assessment.

All patients experienced treatment-related adverse events, largely comprising low-grade injection site reactions and flu-like symptoms linked to the poly-ICLC injections.

One patient experienced grade 3 pembrolizumab-related colitis, while another had self-resolving grade 3 fever following poly-ICLC injection.

The study was sponsored by Icahn School of Medicine at Mount Sinai and conducted in collaboration with Merck Sharp & Dohme LLC and Celldex Therapeutics. No relevant financial relationships were reported.

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

A woman who had breast cancer for 23 years, and who had gone through 12 different lines of therapy, has shown a dramatic response to a novel cancer vaccine in a clinical trial.

A recent 6-month follow-up showed no evidence of new or recurrent disease, and scans showed regression of a distant bulky left adrenal metastasis, as well as at other sites.

A small site of residual hypermetabolism remains in the sternum, but this is thought to be related to scar tissue.

The patient, Stephanie Gangi, told Medscape Medical News that, before she entered into the trial for the novel cancer vaccine, she was “mentally and physically exhausted.” She had benefited from being diagnosed with hormone-positive breast cancer just as its treatment was evolving and progressing, which meant that, every time a treatment failed, “there was the next thing to try, which was great and kept me going.”

“But I will admit that, by age 66, and more than 20 years of cancer treatments, I was exhausted.”

Ms. Gangi, a New York City-based poet, essayist, and fiction writer, said she was “cautiously optimistic” about the cancer vaccine, but the “overriding thought was I wanted to avoid chemotherapy.”

“I was not really signing on for great outcomes, I was signing on for something that might keep chemo at bay. The biggest impact so far for me has been that, for the first time in more than a decade, I am not on any medication. That’s really amazing…and that means no side effects,” she said.

Ms. Gangi stopped the vaccine treatment this past July, and just over 3 months later, she is still “wrapping her head around” the fact that her cancer has regressed. “I’ve had breast cancer a long time,” she said, “and you can’t just snap your fingers and be fine.”

Although the two scans that she has had since the trial ended have been “astonishing,” she underlined that this is not about a ‘cure,’ but rather “clearing tumors for the first time in many years.”

“Cancer is sneaky and sinister, and it figures out how to circumvent all kinds of treatments,” she said, adding nevertheless that she is “happy and hopeful, and my family is thrilled, of course.”

Ms. Gangi was classed as having had a partial response to the cancer vaccine, one of a few in a small phase 1/2 trial at the Icahn School of Medicine at Mount Sinai in New York. One other patient also had a partial response, and one patient had a complete response.

However, six patients have progressive disease, and one has stable disease.  

These results come from an interim analysis of 10 patients from the trial, and show a 30% response rate. They were presented at the recent annual meeting of the Society for Immunotherapy of Cancer.

The vaccine that was being tested combines local low-dose radiation, intramural Flt3L, which stimulates dendritic cells, and intravenous poly-ICLC, an immune stimulating factor, with the PD-1 inhibitor pembrolizumab (Keytruda).

The result is that, instead of making a vaccine in a laboratory and administering it, “we’re actually formulating it within the body,” lead author Thomas Marron, MD, PhD, professor of medicine (hematology and medical oncology) at Mount Sinai, said in an interview.

“What people don’t realize,” he said, is that bulky tumor sites contain “a lot of dead tumor, because they grow so fast and in a haphazard way.” This means that the immune system can be recruited to recognize the dead tumor and “gobble up the dead stuff that’s already there,” he added.

The hope is that the immune system will then kill not only “the tumor you are injecting into, but also tumors elsewhere in the body,” Dr. Marron said. “So you’re basically using your body’s own immune system and on and off switches to vaccinate the patient against their cancer.”

Another patient in the trial who had a complete response to the vaccine was William Morrison, with non-Hodgkin lymphoma (NHL).

Mr. Morrison was diagnosed in 2017, at which time he was enrolled onto a phase 1 trial of an earlier version of this novel vaccine treatment regimen. “Basically, they didn’t get the results they were hoping for, and I still had the lymphoma,” he said. In 2018, his indolent follicular lymphoma transformed into an aggressive diffuse large B-cell lymphoma, for which Mr. Morrison was given six cycles of chemotherapy. This put him into remission and cleared his lymphoma.

“But the remission lasted for maybe a little over a year,” he said.

The cancer came back, and at that point he was given the opportunity to enroll in the Mount Sinai trial. At the end of the treatment, “everything was clear.”

“I’ve been for PET scans every 6 months, and I just had a scan done the other week, and everything has been fine…I’ve been pretty excited. I was pretty lucky.”

“This recent one really has worked wonders,” he said, “When they gave me the good news the other day. I felt like a big weight had been lifted.”

Mr. Morrison also said that he did not experience any serious adverse events while being treated with the vaccine. “Other than a few minor things, I tolerated it pretty well,” he said.

In contrast, Ms. Gangi said she experienced “intense” flu-like symptoms that started in the first few days after the treatment and lasted for a couple of days.
 

Need to improve response rate

The current trial achieved responses in 30% of patients, which “is great, [but] we want to be at 100%,” said Dr. Marron.

“What we’re doing in the laboratory right now is using this as an opportunity to study what it is that’s special about those three people who responded and what’s not happening in the other seven people, and we have some initial data that we’re analyzing,” he said.

“We are seeing that the patients who responded have a much more robust response to the Ft3L in particular…and that could suggest that maybe we need a better Ft3L, or we could think about other ways to potentially manipulate this vaccine.

“Most of the patients who are referred to me are people who have run out of options…and that usually means they’ve had many different types of chemotherapy,” Dr. Marron commented. For example, Ms. Gangi had already been through 12 different chemotherapy regimens.

Chemotherapy suppresses the immune system, but it’s not only that — also having an effect are all the other treatments aimed at reducing nausea and allergic reactions to the anti-cancer therapy, Dr. Marron explained.

“By the time that I see a patient,” Dr. Marron said, “oftentimes their immune system is not optimal. So another way in which we would hope to see better responses is by moving this vaccine earlier in the treatment paradigm, and administering it to patients as their first or second treatment.”

Senior author Joshua Brody, MD, director of the Lymphoma Immunotherapy Program at Mount Sinai’s Tisch Cancer Institute, added that it “might be easy” to incorporate the vaccine into earlier lines of therapy.

He said in an interview that both immunotherapy and radiation therapy are “standard” treatments, and the key is “adding multiple ingredients together that don’t have cumulative toxicity.”

“You can’t just chemo one plus chemo two, because they have some of the same toxicities, but the delightful thing here is this therapy had been quite safe.

“So in theory it would be fairly easy to incorporate this into earlier lines of therapy, once we can get a bit more proof of principle,” Dr. Brody said.

Approached for comment, Ann W. Silk, MD, said that the results are “particularly impressive because we know anti-PD-1 plus radiation therapy does not work in hormone-positive breast cancer or lymphoma.”

Dr. Silk, an oncologist at the Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School in Boston, said in an interview that one advantage of this vaccine is that it “is not restricted to a certain number of antigens and does not rely on an algorithm.”

“I would love to see more data in hormone-positive metastatic breast cancer patients,” she added. “I would use this approach after the hormonal treatments stop working, but before chemotherapy.”

Dr. Silk also said that the safety profile “looks quite good, and I imagine this approach would result in a much better quality of life for patients as compared to chemotherapy.”
 

Details of the trial and results

The Mount Sinai researchers had previously developed a personalized genomic cancer vaccine, PGV-001, which showed promise in a phase 1 trial in 13 patients with solid tumors or multiple myeloma and a high risk of recurrence after surgery or autologous stem cell transplant.

Next, they worked to develop the concept further to turn the tumor into its own vaccine, which involved inducing anti-tumor responses in indolent NHL, which typically responds poorly to checkpoint blockade, by combining Ft3L, low-dose irradiation, and poly-ICLC.

The next phase 1 trial showed that this approach was feasible, but preclinical modeling suggested that the addition of PD-1 blockade could improve the cure rates. The researchers therefore conducted the current trial, recruiting 10 patients with indolent NHL, metastatic breast cancer, or head and neck squamous cell carcinoma (HNSCC).

Patients were given local radiation therapy on days 1 and 2, and intramural Ft3L to the same tumor on day 9, followed by eight intravenous injections of poly-ICLC over 6 weeks. On day 23, they received their first of eight doses of pembrolizumab.

Dr. Marron explained that the radiotherapy increases the amount of dead material for the immune system to work on by “killing some of the tumor cells,” adding: “We’re not trying to kill the whole tumor with the radiation…it just starts the process of releasing some more of that dead stuff.”

He explained that Ft3L is a human growth factor that simulates dendritic cells, “which I always say are the professor cells of the immune system,” as they tell the body “what’s good and what’s bad.”

The poly-ICLC is “basically like a fake virus,” Dr. Marron said, as it “turns on those immune cells that have taken up the tumor antigen in the neighborhood” of the tumor, so they “teach the immune system that there is something bad”.

Finally, the pembrolizumab is there to “take the foot off the brake of the immune system” and “grease the wheels a bit more,” he added, even though it does not work in all patients, or in all tumor types, including indolent NHL.

The trial was planned in two phases. In the first part, six patients were enrolled to assess the safety of the approach; the phase 2 stage of the trial followed a Simon’s Two-Stage design, with the aim of recruiting seven patients of each tumor type, followed by a further 12 patients if they showed a response.

The current interim analysis that was presented at the SITC meeting focused on the first 10 patients in the phase 2 part, who were enrolled between April 2019 and July 2022. This included six patients with metastatic breast cancer, three with indolent NHL, and one with HNSCC, all of whom completed their first disease response assessment.

All patients experienced treatment-related adverse events, largely comprising low-grade injection site reactions and flu-like symptoms linked to the poly-ICLC injections.

One patient experienced grade 3 pembrolizumab-related colitis, while another had self-resolving grade 3 fever following poly-ICLC injection.

The study was sponsored by Icahn School of Medicine at Mount Sinai and conducted in collaboration with Merck Sharp & Dohme LLC and Celldex Therapeutics. No relevant financial relationships were reported.

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

A woman who had breast cancer for 23 years, and who had gone through 12 different lines of therapy, has shown a dramatic response to a novel cancer vaccine in a clinical trial.

A recent 6-month follow-up showed no evidence of new or recurrent disease, and scans showed regression of a distant bulky left adrenal metastasis, as well as at other sites.

A small site of residual hypermetabolism remains in the sternum, but this is thought to be related to scar tissue.

The patient, Stephanie Gangi, told Medscape Medical News that, before she entered into the trial for the novel cancer vaccine, she was “mentally and physically exhausted.” She had benefited from being diagnosed with hormone-positive breast cancer just as its treatment was evolving and progressing, which meant that, every time a treatment failed, “there was the next thing to try, which was great and kept me going.”

“But I will admit that, by age 66, and more than 20 years of cancer treatments, I was exhausted.”

Ms. Gangi, a New York City-based poet, essayist, and fiction writer, said she was “cautiously optimistic” about the cancer vaccine, but the “overriding thought was I wanted to avoid chemotherapy.”

“I was not really signing on for great outcomes, I was signing on for something that might keep chemo at bay. The biggest impact so far for me has been that, for the first time in more than a decade, I am not on any medication. That’s really amazing…and that means no side effects,” she said.

Ms. Gangi stopped the vaccine treatment this past July, and just over 3 months later, she is still “wrapping her head around” the fact that her cancer has regressed. “I’ve had breast cancer a long time,” she said, “and you can’t just snap your fingers and be fine.”

Although the two scans that she has had since the trial ended have been “astonishing,” she underlined that this is not about a ‘cure,’ but rather “clearing tumors for the first time in many years.”

“Cancer is sneaky and sinister, and it figures out how to circumvent all kinds of treatments,” she said, adding nevertheless that she is “happy and hopeful, and my family is thrilled, of course.”

Ms. Gangi was classed as having had a partial response to the cancer vaccine, one of a few in a small phase 1/2 trial at the Icahn School of Medicine at Mount Sinai in New York. One other patient also had a partial response, and one patient had a complete response.

However, six patients have progressive disease, and one has stable disease.  

These results come from an interim analysis of 10 patients from the trial, and show a 30% response rate. They were presented at the recent annual meeting of the Society for Immunotherapy of Cancer.

The vaccine that was being tested combines local low-dose radiation, intramural Flt3L, which stimulates dendritic cells, and intravenous poly-ICLC, an immune stimulating factor, with the PD-1 inhibitor pembrolizumab (Keytruda).

The result is that, instead of making a vaccine in a laboratory and administering it, “we’re actually formulating it within the body,” lead author Thomas Marron, MD, PhD, professor of medicine (hematology and medical oncology) at Mount Sinai, said in an interview.

“What people don’t realize,” he said, is that bulky tumor sites contain “a lot of dead tumor, because they grow so fast and in a haphazard way.” This means that the immune system can be recruited to recognize the dead tumor and “gobble up the dead stuff that’s already there,” he added.

The hope is that the immune system will then kill not only “the tumor you are injecting into, but also tumors elsewhere in the body,” Dr. Marron said. “So you’re basically using your body’s own immune system and on and off switches to vaccinate the patient against their cancer.”

Another patient in the trial who had a complete response to the vaccine was William Morrison, with non-Hodgkin lymphoma (NHL).

Mr. Morrison was diagnosed in 2017, at which time he was enrolled onto a phase 1 trial of an earlier version of this novel vaccine treatment regimen. “Basically, they didn’t get the results they were hoping for, and I still had the lymphoma,” he said. In 2018, his indolent follicular lymphoma transformed into an aggressive diffuse large B-cell lymphoma, for which Mr. Morrison was given six cycles of chemotherapy. This put him into remission and cleared his lymphoma.

“But the remission lasted for maybe a little over a year,” he said.

The cancer came back, and at that point he was given the opportunity to enroll in the Mount Sinai trial. At the end of the treatment, “everything was clear.”

“I’ve been for PET scans every 6 months, and I just had a scan done the other week, and everything has been fine…I’ve been pretty excited. I was pretty lucky.”

“This recent one really has worked wonders,” he said, “When they gave me the good news the other day. I felt like a big weight had been lifted.”

Mr. Morrison also said that he did not experience any serious adverse events while being treated with the vaccine. “Other than a few minor things, I tolerated it pretty well,” he said.

In contrast, Ms. Gangi said she experienced “intense” flu-like symptoms that started in the first few days after the treatment and lasted for a couple of days.
 

Need to improve response rate

The current trial achieved responses in 30% of patients, which “is great, [but] we want to be at 100%,” said Dr. Marron.

“What we’re doing in the laboratory right now is using this as an opportunity to study what it is that’s special about those three people who responded and what’s not happening in the other seven people, and we have some initial data that we’re analyzing,” he said.

“We are seeing that the patients who responded have a much more robust response to the Ft3L in particular…and that could suggest that maybe we need a better Ft3L, or we could think about other ways to potentially manipulate this vaccine.

“Most of the patients who are referred to me are people who have run out of options…and that usually means they’ve had many different types of chemotherapy,” Dr. Marron commented. For example, Ms. Gangi had already been through 12 different chemotherapy regimens.

Chemotherapy suppresses the immune system, but it’s not only that — also having an effect are all the other treatments aimed at reducing nausea and allergic reactions to the anti-cancer therapy, Dr. Marron explained.

“By the time that I see a patient,” Dr. Marron said, “oftentimes their immune system is not optimal. So another way in which we would hope to see better responses is by moving this vaccine earlier in the treatment paradigm, and administering it to patients as their first or second treatment.”

Senior author Joshua Brody, MD, director of the Lymphoma Immunotherapy Program at Mount Sinai’s Tisch Cancer Institute, added that it “might be easy” to incorporate the vaccine into earlier lines of therapy.

He said in an interview that both immunotherapy and radiation therapy are “standard” treatments, and the key is “adding multiple ingredients together that don’t have cumulative toxicity.”

“You can’t just chemo one plus chemo two, because they have some of the same toxicities, but the delightful thing here is this therapy had been quite safe.

“So in theory it would be fairly easy to incorporate this into earlier lines of therapy, once we can get a bit more proof of principle,” Dr. Brody said.

Approached for comment, Ann W. Silk, MD, said that the results are “particularly impressive because we know anti-PD-1 plus radiation therapy does not work in hormone-positive breast cancer or lymphoma.”

Dr. Silk, an oncologist at the Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School in Boston, said in an interview that one advantage of this vaccine is that it “is not restricted to a certain number of antigens and does not rely on an algorithm.”

“I would love to see more data in hormone-positive metastatic breast cancer patients,” she added. “I would use this approach after the hormonal treatments stop working, but before chemotherapy.”

Dr. Silk also said that the safety profile “looks quite good, and I imagine this approach would result in a much better quality of life for patients as compared to chemotherapy.”
 

Details of the trial and results

The Mount Sinai researchers had previously developed a personalized genomic cancer vaccine, PGV-001, which showed promise in a phase 1 trial in 13 patients with solid tumors or multiple myeloma and a high risk of recurrence after surgery or autologous stem cell transplant.

Next, they worked to develop the concept further to turn the tumor into its own vaccine, which involved inducing anti-tumor responses in indolent NHL, which typically responds poorly to checkpoint blockade, by combining Ft3L, low-dose irradiation, and poly-ICLC.

The next phase 1 trial showed that this approach was feasible, but preclinical modeling suggested that the addition of PD-1 blockade could improve the cure rates. The researchers therefore conducted the current trial, recruiting 10 patients with indolent NHL, metastatic breast cancer, or head and neck squamous cell carcinoma (HNSCC).

Patients were given local radiation therapy on days 1 and 2, and intramural Ft3L to the same tumor on day 9, followed by eight intravenous injections of poly-ICLC over 6 weeks. On day 23, they received their first of eight doses of pembrolizumab.

Dr. Marron explained that the radiotherapy increases the amount of dead material for the immune system to work on by “killing some of the tumor cells,” adding: “We’re not trying to kill the whole tumor with the radiation…it just starts the process of releasing some more of that dead stuff.”

He explained that Ft3L is a human growth factor that simulates dendritic cells, “which I always say are the professor cells of the immune system,” as they tell the body “what’s good and what’s bad.”

The poly-ICLC is “basically like a fake virus,” Dr. Marron said, as it “turns on those immune cells that have taken up the tumor antigen in the neighborhood” of the tumor, so they “teach the immune system that there is something bad”.

Finally, the pembrolizumab is there to “take the foot off the brake of the immune system” and “grease the wheels a bit more,” he added, even though it does not work in all patients, or in all tumor types, including indolent NHL.

The trial was planned in two phases. In the first part, six patients were enrolled to assess the safety of the approach; the phase 2 stage of the trial followed a Simon’s Two-Stage design, with the aim of recruiting seven patients of each tumor type, followed by a further 12 patients if they showed a response.

The current interim analysis that was presented at the SITC meeting focused on the first 10 patients in the phase 2 part, who were enrolled between April 2019 and July 2022. This included six patients with metastatic breast cancer, three with indolent NHL, and one with HNSCC, all of whom completed their first disease response assessment.

All patients experienced treatment-related adverse events, largely comprising low-grade injection site reactions and flu-like symptoms linked to the poly-ICLC injections.

One patient experienced grade 3 pembrolizumab-related colitis, while another had self-resolving grade 3 fever following poly-ICLC injection.

The study was sponsored by Icahn School of Medicine at Mount Sinai and conducted in collaboration with Merck Sharp & Dohme LLC and Celldex Therapeutics. No relevant financial relationships were reported.

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

Medical residents have cleared many hurdles to get where they are, as detailed in Medscape’s Residents Salary and Debt Report 2022 which explains their challenges with compensation and school loans as well as long hours and problematic personal relationships.

Whereas 72% of residents described themselves as “very satisfied” or “satisfied” with their professional training experience, only 27% felt that highly about how well they’re paid. Satisfaction levels increased somewhat farther into residency, reaching 35% in year 5.

Respondents to the survey described mixed feelings about residency, with some concluding it is a rite of passage.
 

Do residents have it easier today?

If so, is that rite of passage getting any easier? You’ll get different answers from residents and physicians.

Medscape asked respondents whether their journey to residency was made easier once the Step 1 exam was converted to pass-fail, and interviews brought online, because of the COVID-19 pandemic.

Many residents conceded their journey became easier, less stressful, and less expensive under the new Step 1 formats. One respondent said he was freed up to focus more intently on higher-yield academic goals such as research.

Another respondent called the pass/fail change a “total game-changer,” as it lets applicants apply to all specialties while having other qualifications than test scores considered. A resident who took Step 1 before pass/fail was instituted described the “insurmountable stress associated with studying for Step 1 to get the highest score you possibly could.”

But not all residents liked the difficulty in being able to differentiate themselves, beyond med school pedigrees, in the absence of Step 1 scores.

Meanwhile, some doctors posting comments to the Medscape report strongly disagreed with the idea that residency life is getting harder. They depict residency as a rite of passage under the best of circumstances.

“Whatever issues there may be [today’s residents] are still making eight times what I got and, from what I’ve seen, we had a lot more independent responsibilities,” one physician commenter said.

Other doctors were more sympathetic and worried about the future price to be paid for hardships during residency. “Compensation should not be tied to the willingness to sacrifice the most beautiful years of life,” one commentator wrote.
 

Online interviews: Pros and cons

Many resident respondents celebrated the opportunity to interview for residency programs online. Some who traveled to in-person interviews before the pandemic said they racked up as much as $10,000 in travel costs, adding to their debt loads.

But not everyone was a fan. Other residents sniped that peers can apply to more residencies and “hoard” interviews, making the competition that much harder.

And how useful are online interviews to a prospective resident? “Virtual interviews are terrible for getting a true sense for a program or even the people,” a 1st-year family medicine resident complained. And it’s harder for an applicant “to shine when you’re on Zoom,” a 1st-year internal medicine resident opined.
 

Whether to report harassment

In survey, respondents were asked whether they ever witnessed sexual abuse, harassment, or misconduct; and if so, what they did about it. Among those who did, many opted to take no action, fearing retaliation or retribution. “I saw a resident made out to be a ‘problem resident’ when reporting it and then ultimately fired,” one respondent recounted.

Other residents said they felt unsure about the protocol, whom to report to, or even what constituted harassment or misconduct. “I didn’t realize [an incident] was harassment until later,” one resident said. Others thought “minor” or “subtle” incidents did not warrant action; “they are typically microaggressions and appear accepted within the culture of the institution.”

Residents’ confusion heightened when the perpetrator was a patient. “I’m not sure what to do about that,” a respondent acknowledged. An emergency medicine resident added, “most of the time … it is the patients who are acting inappropriately, saying inappropriate things, etc. There is no way to file a complaint like that.”
 

Rewards and challenges for residents

Among the most rewarding parts of residency that respondents described were developing specific skills such as surgical techniques, job security, and “learning a little day by day” in the words of a 1st-year gastroenterology resident.

Others felt gratified by the chances to help patients and families, their teams, and to advance social justice and health equity.

But challenges abound – chiefly money struggles. A 3rd-year psychiatry resident lamented “being financially strapped in the prime of my life from student loans and low wages.”

Stress and emotional fatigue also came up often as major challenges. “Constantly being told to do more, more presentations, more papers, more research, more studying,” a 5th-year neurosurgery resident bemoaned. “Being expected to be at the top of my game despite being sleep-deprived, depressed, and burned out,” a 3rd-year ob.gyn. resident groused.

But some physician commenters urged residents to look for long-term growth behind the challenges. “Yes, it was hard, but the experience was phenomenal, and I am glad I did it,” one doctor said.

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

Medical residents have cleared many hurdles to get where they are, as detailed in Medscape’s Residents Salary and Debt Report 2022 which explains their challenges with compensation and school loans as well as long hours and problematic personal relationships.

Whereas 72% of residents described themselves as “very satisfied” or “satisfied” with their professional training experience, only 27% felt that highly about how well they’re paid. Satisfaction levels increased somewhat farther into residency, reaching 35% in year 5.

Respondents to the survey described mixed feelings about residency, with some concluding it is a rite of passage.
 

Do residents have it easier today?

If so, is that rite of passage getting any easier? You’ll get different answers from residents and physicians.

Medscape asked respondents whether their journey to residency was made easier once the Step 1 exam was converted to pass-fail, and interviews brought online, because of the COVID-19 pandemic.

Many residents conceded their journey became easier, less stressful, and less expensive under the new Step 1 formats. One respondent said he was freed up to focus more intently on higher-yield academic goals such as research.

Another respondent called the pass/fail change a “total game-changer,” as it lets applicants apply to all specialties while having other qualifications than test scores considered. A resident who took Step 1 before pass/fail was instituted described the “insurmountable stress associated with studying for Step 1 to get the highest score you possibly could.”

But not all residents liked the difficulty in being able to differentiate themselves, beyond med school pedigrees, in the absence of Step 1 scores.

Meanwhile, some doctors posting comments to the Medscape report strongly disagreed with the idea that residency life is getting harder. They depict residency as a rite of passage under the best of circumstances.

“Whatever issues there may be [today’s residents] are still making eight times what I got and, from what I’ve seen, we had a lot more independent responsibilities,” one physician commenter said.

Other doctors were more sympathetic and worried about the future price to be paid for hardships during residency. “Compensation should not be tied to the willingness to sacrifice the most beautiful years of life,” one commentator wrote.
 

Online interviews: Pros and cons

Many resident respondents celebrated the opportunity to interview for residency programs online. Some who traveled to in-person interviews before the pandemic said they racked up as much as $10,000 in travel costs, adding to their debt loads.

But not everyone was a fan. Other residents sniped that peers can apply to more residencies and “hoard” interviews, making the competition that much harder.

And how useful are online interviews to a prospective resident? “Virtual interviews are terrible for getting a true sense for a program or even the people,” a 1st-year family medicine resident complained. And it’s harder for an applicant “to shine when you’re on Zoom,” a 1st-year internal medicine resident opined.
 

Whether to report harassment

In survey, respondents were asked whether they ever witnessed sexual abuse, harassment, or misconduct; and if so, what they did about it. Among those who did, many opted to take no action, fearing retaliation or retribution. “I saw a resident made out to be a ‘problem resident’ when reporting it and then ultimately fired,” one respondent recounted.

Other residents said they felt unsure about the protocol, whom to report to, or even what constituted harassment or misconduct. “I didn’t realize [an incident] was harassment until later,” one resident said. Others thought “minor” or “subtle” incidents did not warrant action; “they are typically microaggressions and appear accepted within the culture of the institution.”

Residents’ confusion heightened when the perpetrator was a patient. “I’m not sure what to do about that,” a respondent acknowledged. An emergency medicine resident added, “most of the time … it is the patients who are acting inappropriately, saying inappropriate things, etc. There is no way to file a complaint like that.”
 

Rewards and challenges for residents

Among the most rewarding parts of residency that respondents described were developing specific skills such as surgical techniques, job security, and “learning a little day by day” in the words of a 1st-year gastroenterology resident.

Others felt gratified by the chances to help patients and families, their teams, and to advance social justice and health equity.

But challenges abound – chiefly money struggles. A 3rd-year psychiatry resident lamented “being financially strapped in the prime of my life from student loans and low wages.”

Stress and emotional fatigue also came up often as major challenges. “Constantly being told to do more, more presentations, more papers, more research, more studying,” a 5th-year neurosurgery resident bemoaned. “Being expected to be at the top of my game despite being sleep-deprived, depressed, and burned out,” a 3rd-year ob.gyn. resident groused.

But some physician commenters urged residents to look for long-term growth behind the challenges. “Yes, it was hard, but the experience was phenomenal, and I am glad I did it,” one doctor said.

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

Medical residents have cleared many hurdles to get where they are, as detailed in Medscape’s Residents Salary and Debt Report 2022 which explains their challenges with compensation and school loans as well as long hours and problematic personal relationships.

Whereas 72% of residents described themselves as “very satisfied” or “satisfied” with their professional training experience, only 27% felt that highly about how well they’re paid. Satisfaction levels increased somewhat farther into residency, reaching 35% in year 5.

Respondents to the survey described mixed feelings about residency, with some concluding it is a rite of passage.
 

Do residents have it easier today?

If so, is that rite of passage getting any easier? You’ll get different answers from residents and physicians.

Medscape asked respondents whether their journey to residency was made easier once the Step 1 exam was converted to pass-fail, and interviews brought online, because of the COVID-19 pandemic.

Many residents conceded their journey became easier, less stressful, and less expensive under the new Step 1 formats. One respondent said he was freed up to focus more intently on higher-yield academic goals such as research.

Another respondent called the pass/fail change a “total game-changer,” as it lets applicants apply to all specialties while having other qualifications than test scores considered. A resident who took Step 1 before pass/fail was instituted described the “insurmountable stress associated with studying for Step 1 to get the highest score you possibly could.”

But not all residents liked the difficulty in being able to differentiate themselves, beyond med school pedigrees, in the absence of Step 1 scores.

Meanwhile, some doctors posting comments to the Medscape report strongly disagreed with the idea that residency life is getting harder. They depict residency as a rite of passage under the best of circumstances.

“Whatever issues there may be [today’s residents] are still making eight times what I got and, from what I’ve seen, we had a lot more independent responsibilities,” one physician commenter said.

Other doctors were more sympathetic and worried about the future price to be paid for hardships during residency. “Compensation should not be tied to the willingness to sacrifice the most beautiful years of life,” one commentator wrote.
 

Online interviews: Pros and cons

Many resident respondents celebrated the opportunity to interview for residency programs online. Some who traveled to in-person interviews before the pandemic said they racked up as much as $10,000 in travel costs, adding to their debt loads.

But not everyone was a fan. Other residents sniped that peers can apply to more residencies and “hoard” interviews, making the competition that much harder.

And how useful are online interviews to a prospective resident? “Virtual interviews are terrible for getting a true sense for a program or even the people,” a 1st-year family medicine resident complained. And it’s harder for an applicant “to shine when you’re on Zoom,” a 1st-year internal medicine resident opined.
 

Whether to report harassment

In survey, respondents were asked whether they ever witnessed sexual abuse, harassment, or misconduct; and if so, what they did about it. Among those who did, many opted to take no action, fearing retaliation or retribution. “I saw a resident made out to be a ‘problem resident’ when reporting it and then ultimately fired,” one respondent recounted.

Other residents said they felt unsure about the protocol, whom to report to, or even what constituted harassment or misconduct. “I didn’t realize [an incident] was harassment until later,” one resident said. Others thought “minor” or “subtle” incidents did not warrant action; “they are typically microaggressions and appear accepted within the culture of the institution.”

Residents’ confusion heightened when the perpetrator was a patient. “I’m not sure what to do about that,” a respondent acknowledged. An emergency medicine resident added, “most of the time … it is the patients who are acting inappropriately, saying inappropriate things, etc. There is no way to file a complaint like that.”
 

Rewards and challenges for residents

Among the most rewarding parts of residency that respondents described were developing specific skills such as surgical techniques, job security, and “learning a little day by day” in the words of a 1st-year gastroenterology resident.

Others felt gratified by the chances to help patients and families, their teams, and to advance social justice and health equity.

But challenges abound – chiefly money struggles. A 3rd-year psychiatry resident lamented “being financially strapped in the prime of my life from student loans and low wages.”

Stress and emotional fatigue also came up often as major challenges. “Constantly being told to do more, more presentations, more papers, more research, more studying,” a 5th-year neurosurgery resident bemoaned. “Being expected to be at the top of my game despite being sleep-deprived, depressed, and burned out,” a 3rd-year ob.gyn. resident groused.

But some physician commenters urged residents to look for long-term growth behind the challenges. “Yes, it was hard, but the experience was phenomenal, and I am glad I did it,” one doctor said.

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

Emergencies happen anywhere, anytime – and sometimes physicians find themselves in situations where they are the only ones who can help. “Is There a Doctor in the House?” is a new series telling these stories.

When the plane crashed, I was asleep. I had arrived the evening before with my wife and three sons at a house on Kezar Lake on the Maine–New Hampshire border. We were going to spend a week there with my wife’s four brothers and their families. I was woken by people screaming my name. I jumped out of bed and ran downstairs. My kids had been watching a float plane circling and gliding along the lake. It had crashed into the water and flipped upside down. My oldest brother-in-law jumped into his ski boat and we sped out to the scene.

All we can see are the plane’s pontoons. The rest is underwater. A woman has already surfaced, screaming. I dive in.

I find the woman’s husband and 3-year-old son struggling to get free from the plane through the smashed windshield. They manage to get to the surface. The pilot is dead, impaled through the chest by the left wing strut.

The big problem: A little girl, whom I would learn later is named Lauren, remained trapped. The water is murky but I can see her, a 5- or 6-year-old girl with this long hair, strapped in upside down and unconscious.

The mom and I dive down over and over, pulling and ripping at the door. We cannot get it open. Finally, I’m able to bend the door open enough where I can reach in, but I can’t undo the seatbelt. In my mind, I’m debating, should I try and go through the front windshield? I’m getting really tired, I can tell there’s fuel in the water, and I don’t want to drown in the plane. So I pop up to the surface and yell, “Does anyone have a knife?”

My brother-in-law shoots back to shore in the boat, screaming, “Get a knife!” My niece gets in the boat with one. I’m standing on the pontoon, and my niece is in the front of the boat calling, “Uncle Todd! Uncle Todd!” and she throws the knife. It goes way over my head. I can’t even jump for it, it’s so high.

I have to get the knife. So, I dive into the water to try and find it. Somehow, the black knife has landed on the white wing, 4 or 5 feet under the water. Pure luck. It could have sunk down a hundred feet into the lake. I grab the knife and hand it to the mom, Beth. She’s able to cut the seatbelt, and we both pull Lauren to the surface.

I lay her out on the pontoon. She has no pulse and her pupils are fixed and dilated. Her mom is yelling, “She’s dead, isn’t she?” I start CPR. My skin and eyes are burning from the airplane fuel in the water. I get her breathing, and her heart comes back very quickly. Lauren starts to vomit and I’m trying to keep her airway clear. She’s breathing spontaneously and she has a pulse, so I decide it’s time to move her to shore.

We pull the boat up to the dock and Lauren’s now having anoxic seizures. Her brain has been without oxygen, and now she’s getting perfused again. We get her to shore and lay her on the lawn. I’m still doing mouth-to-mouth, but she’s seizing like crazy, and I don’t have any way to control that. Beth is crying and wants to hold her daughter gently while I’m working.

Someone had called 911, and finally this dude shows up with an ambulance, and it’s like something out of World War II. All he has is an oxygen tank, but the mask is old and cracked. It’s too big for Lauren, but it sort of fits me, so I’m sucking in oxygen and blowing it into the girl’s mouth. I’m doing whatever I can, but I don’t have an IV to start. I have no fluids. I got nothing.

As it happens, I’d done my emergency medicine training at Maine Medical Center, so I tell someone to call them and get a Life Flight chopper. We have to drive somewhere where the chopper can land, so we take the ambulance to the parking lot of the closest store called the Wicked Good Store. That’s a common thing in Maine. Everything is “wicked good.”

The whole town is there by that point. The chopper arrives. The ambulance doors pop open and a woman says, “Todd?” And I say, “Heather?”

Heather is an emergency flight nurse whom I’d trained with many years ago. There’s immediate trust. She has all the right equipment. We put in breathing tubes and IVs. We stop Lauren from seizing. The kid is soon stable.

There is only one extra seat in the chopper, so I tell Beth to go. They take off.

Suddenly, I begin to doubt my decision. Lauren had been underwater for 15 minutes at minimum. I know how long that is. Did I do the right thing? Did I resuscitate a brain-dead child? I didn’t think about it at the time, but if that patient had come to me in the emergency department, I’m honestly not sure what I would have done.

So, I go home. And I don’t get a call. The FAA and sheriff arrive to take statements from us. I don’t hear from anyone.

The next day I start calling. No one will tell me anything, so I finally get to one of the pediatric ICU attendings who had trained me. He says Lauren literally woke up and said, “I have to go pee.” And that was it. She was 100% normal. I couldn’t believe it.

Here’s a theory: In kids, there’s something called the glottic reflex. I think her glottic reflex went off as soon as she hit the water, which basically closed her airway. So when she passed out, she could never get enough water in her lungs and still had enough air in there to keep her alive. Later, I got a call from her uncle. He could barely get the words out because he was in tears. He said Lauren was doing beautifully.  

Three days later, I drove to Lauren’s house with my wife and kids. I had her read to me. I watched her play on the jungle gym for motor function. All sorts of stuff. She was totally normal.

Beth told us that the night before the accident, her mother had given the women in her family what she called a “miracle bracelet,” a bracelet that is supposed to give you one miracle in your life. Beth said she had the bracelet on her wrist the day of the accident, and now it’s gone. “Saving Lauren’s life was my miracle,” she said.

Funny thing: For 20 years, I ran all the EMS, police, fire, ambulance, in Boulder, Colo., where I live. I wrote all the protocols, and I would never advise any of my paramedics to dive into jet fuel to save someone. That was risky. But at the time, it was totally automatic. I think it taught me not to give up in certain situations, because you really don’t know.

Dr. Dorfman is an emergency medicine physician in Boulder, Colo., and medical director at Cedalion Health.
 

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

Emergencies happen anywhere, anytime – and sometimes physicians find themselves in situations where they are the only ones who can help. “Is There a Doctor in the House?” is a new series telling these stories.

When the plane crashed, I was asleep. I had arrived the evening before with my wife and three sons at a house on Kezar Lake on the Maine–New Hampshire border. We were going to spend a week there with my wife’s four brothers and their families. I was woken by people screaming my name. I jumped out of bed and ran downstairs. My kids had been watching a float plane circling and gliding along the lake. It had crashed into the water and flipped upside down. My oldest brother-in-law jumped into his ski boat and we sped out to the scene.

All we can see are the plane’s pontoons. The rest is underwater. A woman has already surfaced, screaming. I dive in.

I find the woman’s husband and 3-year-old son struggling to get free from the plane through the smashed windshield. They manage to get to the surface. The pilot is dead, impaled through the chest by the left wing strut.

The big problem: A little girl, whom I would learn later is named Lauren, remained trapped. The water is murky but I can see her, a 5- or 6-year-old girl with this long hair, strapped in upside down and unconscious.

The mom and I dive down over and over, pulling and ripping at the door. We cannot get it open. Finally, I’m able to bend the door open enough where I can reach in, but I can’t undo the seatbelt. In my mind, I’m debating, should I try and go through the front windshield? I’m getting really tired, I can tell there’s fuel in the water, and I don’t want to drown in the plane. So I pop up to the surface and yell, “Does anyone have a knife?”

My brother-in-law shoots back to shore in the boat, screaming, “Get a knife!” My niece gets in the boat with one. I’m standing on the pontoon, and my niece is in the front of the boat calling, “Uncle Todd! Uncle Todd!” and she throws the knife. It goes way over my head. I can’t even jump for it, it’s so high.

I have to get the knife. So, I dive into the water to try and find it. Somehow, the black knife has landed on the white wing, 4 or 5 feet under the water. Pure luck. It could have sunk down a hundred feet into the lake. I grab the knife and hand it to the mom, Beth. She’s able to cut the seatbelt, and we both pull Lauren to the surface.

I lay her out on the pontoon. She has no pulse and her pupils are fixed and dilated. Her mom is yelling, “She’s dead, isn’t she?” I start CPR. My skin and eyes are burning from the airplane fuel in the water. I get her breathing, and her heart comes back very quickly. Lauren starts to vomit and I’m trying to keep her airway clear. She’s breathing spontaneously and she has a pulse, so I decide it’s time to move her to shore.

We pull the boat up to the dock and Lauren’s now having anoxic seizures. Her brain has been without oxygen, and now she’s getting perfused again. We get her to shore and lay her on the lawn. I’m still doing mouth-to-mouth, but she’s seizing like crazy, and I don’t have any way to control that. Beth is crying and wants to hold her daughter gently while I’m working.

Someone had called 911, and finally this dude shows up with an ambulance, and it’s like something out of World War II. All he has is an oxygen tank, but the mask is old and cracked. It’s too big for Lauren, but it sort of fits me, so I’m sucking in oxygen and blowing it into the girl’s mouth. I’m doing whatever I can, but I don’t have an IV to start. I have no fluids. I got nothing.

As it happens, I’d done my emergency medicine training at Maine Medical Center, so I tell someone to call them and get a Life Flight chopper. We have to drive somewhere where the chopper can land, so we take the ambulance to the parking lot of the closest store called the Wicked Good Store. That’s a common thing in Maine. Everything is “wicked good.”

The whole town is there by that point. The chopper arrives. The ambulance doors pop open and a woman says, “Todd?” And I say, “Heather?”

Heather is an emergency flight nurse whom I’d trained with many years ago. There’s immediate trust. She has all the right equipment. We put in breathing tubes and IVs. We stop Lauren from seizing. The kid is soon stable.

There is only one extra seat in the chopper, so I tell Beth to go. They take off.

Suddenly, I begin to doubt my decision. Lauren had been underwater for 15 minutes at minimum. I know how long that is. Did I do the right thing? Did I resuscitate a brain-dead child? I didn’t think about it at the time, but if that patient had come to me in the emergency department, I’m honestly not sure what I would have done.

So, I go home. And I don’t get a call. The FAA and sheriff arrive to take statements from us. I don’t hear from anyone.

The next day I start calling. No one will tell me anything, so I finally get to one of the pediatric ICU attendings who had trained me. He says Lauren literally woke up and said, “I have to go pee.” And that was it. She was 100% normal. I couldn’t believe it.

Here’s a theory: In kids, there’s something called the glottic reflex. I think her glottic reflex went off as soon as she hit the water, which basically closed her airway. So when she passed out, she could never get enough water in her lungs and still had enough air in there to keep her alive. Later, I got a call from her uncle. He could barely get the words out because he was in tears. He said Lauren was doing beautifully.  

Three days later, I drove to Lauren’s house with my wife and kids. I had her read to me. I watched her play on the jungle gym for motor function. All sorts of stuff. She was totally normal.

Beth told us that the night before the accident, her mother had given the women in her family what she called a “miracle bracelet,” a bracelet that is supposed to give you one miracle in your life. Beth said she had the bracelet on her wrist the day of the accident, and now it’s gone. “Saving Lauren’s life was my miracle,” she said.

Funny thing: For 20 years, I ran all the EMS, police, fire, ambulance, in Boulder, Colo., where I live. I wrote all the protocols, and I would never advise any of my paramedics to dive into jet fuel to save someone. That was risky. But at the time, it was totally automatic. I think it taught me not to give up in certain situations, because you really don’t know.

Dr. Dorfman is an emergency medicine physician in Boulder, Colo., and medical director at Cedalion Health.
 

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

Emergencies happen anywhere, anytime – and sometimes physicians find themselves in situations where they are the only ones who can help. “Is There a Doctor in the House?” is a new series telling these stories.

When the plane crashed, I was asleep. I had arrived the evening before with my wife and three sons at a house on Kezar Lake on the Maine–New Hampshire border. We were going to spend a week there with my wife’s four brothers and their families. I was woken by people screaming my name. I jumped out of bed and ran downstairs. My kids had been watching a float plane circling and gliding along the lake. It had crashed into the water and flipped upside down. My oldest brother-in-law jumped into his ski boat and we sped out to the scene.

All we can see are the plane’s pontoons. The rest is underwater. A woman has already surfaced, screaming. I dive in.

I find the woman’s husband and 3-year-old son struggling to get free from the plane through the smashed windshield. They manage to get to the surface. The pilot is dead, impaled through the chest by the left wing strut.

The big problem: A little girl, whom I would learn later is named Lauren, remained trapped. The water is murky but I can see her, a 5- or 6-year-old girl with this long hair, strapped in upside down and unconscious.

The mom and I dive down over and over, pulling and ripping at the door. We cannot get it open. Finally, I’m able to bend the door open enough where I can reach in, but I can’t undo the seatbelt. In my mind, I’m debating, should I try and go through the front windshield? I’m getting really tired, I can tell there’s fuel in the water, and I don’t want to drown in the plane. So I pop up to the surface and yell, “Does anyone have a knife?”

My brother-in-law shoots back to shore in the boat, screaming, “Get a knife!” My niece gets in the boat with one. I’m standing on the pontoon, and my niece is in the front of the boat calling, “Uncle Todd! Uncle Todd!” and she throws the knife. It goes way over my head. I can’t even jump for it, it’s so high.

I have to get the knife. So, I dive into the water to try and find it. Somehow, the black knife has landed on the white wing, 4 or 5 feet under the water. Pure luck. It could have sunk down a hundred feet into the lake. I grab the knife and hand it to the mom, Beth. She’s able to cut the seatbelt, and we both pull Lauren to the surface.

I lay her out on the pontoon. She has no pulse and her pupils are fixed and dilated. Her mom is yelling, “She’s dead, isn’t she?” I start CPR. My skin and eyes are burning from the airplane fuel in the water. I get her breathing, and her heart comes back very quickly. Lauren starts to vomit and I’m trying to keep her airway clear. She’s breathing spontaneously and she has a pulse, so I decide it’s time to move her to shore.

We pull the boat up to the dock and Lauren’s now having anoxic seizures. Her brain has been without oxygen, and now she’s getting perfused again. We get her to shore and lay her on the lawn. I’m still doing mouth-to-mouth, but she’s seizing like crazy, and I don’t have any way to control that. Beth is crying and wants to hold her daughter gently while I’m working.

Someone had called 911, and finally this dude shows up with an ambulance, and it’s like something out of World War II. All he has is an oxygen tank, but the mask is old and cracked. It’s too big for Lauren, but it sort of fits me, so I’m sucking in oxygen and blowing it into the girl’s mouth. I’m doing whatever I can, but I don’t have an IV to start. I have no fluids. I got nothing.

As it happens, I’d done my emergency medicine training at Maine Medical Center, so I tell someone to call them and get a Life Flight chopper. We have to drive somewhere where the chopper can land, so we take the ambulance to the parking lot of the closest store called the Wicked Good Store. That’s a common thing in Maine. Everything is “wicked good.”

The whole town is there by that point. The chopper arrives. The ambulance doors pop open and a woman says, “Todd?” And I say, “Heather?”

Heather is an emergency flight nurse whom I’d trained with many years ago. There’s immediate trust. She has all the right equipment. We put in breathing tubes and IVs. We stop Lauren from seizing. The kid is soon stable.

There is only one extra seat in the chopper, so I tell Beth to go. They take off.

Suddenly, I begin to doubt my decision. Lauren had been underwater for 15 minutes at minimum. I know how long that is. Did I do the right thing? Did I resuscitate a brain-dead child? I didn’t think about it at the time, but if that patient had come to me in the emergency department, I’m honestly not sure what I would have done.

So, I go home. And I don’t get a call. The FAA and sheriff arrive to take statements from us. I don’t hear from anyone.

The next day I start calling. No one will tell me anything, so I finally get to one of the pediatric ICU attendings who had trained me. He says Lauren literally woke up and said, “I have to go pee.” And that was it. She was 100% normal. I couldn’t believe it.

Here’s a theory: In kids, there’s something called the glottic reflex. I think her glottic reflex went off as soon as she hit the water, which basically closed her airway. So when she passed out, she could never get enough water in her lungs and still had enough air in there to keep her alive. Later, I got a call from her uncle. He could barely get the words out because he was in tears. He said Lauren was doing beautifully.  

Three days later, I drove to Lauren’s house with my wife and kids. I had her read to me. I watched her play on the jungle gym for motor function. All sorts of stuff. She was totally normal.

Beth told us that the night before the accident, her mother had given the women in her family what she called a “miracle bracelet,” a bracelet that is supposed to give you one miracle in your life. Beth said she had the bracelet on her wrist the day of the accident, and now it’s gone. “Saving Lauren’s life was my miracle,” she said.

Funny thing: For 20 years, I ran all the EMS, police, fire, ambulance, in Boulder, Colo., where I live. I wrote all the protocols, and I would never advise any of my paramedics to dive into jet fuel to save someone. That was risky. But at the time, it was totally automatic. I think it taught me not to give up in certain situations, because you really don’t know.

Dr. Dorfman is an emergency medicine physician in Boulder, Colo., and medical director at Cedalion Health.
 

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

PHILADELPHIA – What works in the clinic can also work in community settings: Patients who are overweight or obese with knee osteoarthritis can find relief from pain through diet and exercise programs conducted in recreation centers, local gyms, fitness centers, and other places close to home, according to investigators in a pragmatic randomized trial.

The Weight Loss and Exercise for Communities With Arthritis in North Carolina (WE-CAN) study was modeled after the successful Intensive Diet and Exercise for Arthritis trial, which showed that adults randomized to 18 months of either a diet and exercise program or diet alone had more weight loss and larger reductions in levels of the inflammatory cytokine interleukin-6 than patients randomized to exercise alone, and that diet alone was associated with greater reductions in knee compressive force than exercise alone.

That study was conducted by Stephen P. Messier, PhD, and colleagues at Wake Forest University, Winston-Salem, N.C.. As previously reported, the investigators also saw continued benefits for participants years after the original trial.

With the WE-CAN trial, results of which were reported at the annual meeting of the American College of Rheumatology, Dr. Messier and colleagues took the intervention one step further, randomizing 823 community-dwelling adults who were overweight or obese (body mass index [BMI], ≥ 27 kg/m2) with knee OA to either an 18-month diet and exercise intervention or attention control group consisting of five 1-hour face-to-face meetings over 18 months, plus information packets and phone sessions during alternate months.

“Compared to the control group, diet plus exercise had a statistically significant but modest reduction in pain. Diet plus exercise was 20% more likely to attain a clinically important 2-point improvement in pain,” Dr. Messier said in an oral abstract session at ACR.
 

Real-world setting

The primary goal of WE-CAN was to “determine whether adaptation of a diet and exercise academic center–based efficacy trial to community settings results in a statistically significant reduction in pain relative to an attention control.”

Ariel Skelley/Getty Images

A total of 3,751 potential candidates were screened, and 823 were randomized and assigned to either a diet and exercise arm (414) or attention control arm (409). Of the patients randomized, 336 in the diet/exercise arm and 322 in the control arm attended the final 18-month follow-up visit.

The exercise component consisted of a 15-minute walking period, followed by a 20-minute weight-training period, and ending with a second 15-minute walking period. The diet goal was 10% or greater weight loss, aided by a distribution of low-calorie recipes to produce a reduced-calorie diet of the patient’s choice, with the option to include nutritional powder to make low-calories shakes as meal replacements, one or two per day for the first 6 months, with the option of one per day for the remaining months.

The pragmatic components included the use of established community facilities in both urban and rural counties in North Carolina, broad inclusion criteria, patient-centered outcomes, use of community-based staff to deliver the treatment, nonphysicians trained by study physicians to perform knee exams, and various means of communication, Dr. Messier said.

Participants in each arm were closely matched by demographic and clinical characteristics, with a mean age of 64.5 years in the diet/exercise group and 64.7 years in the attention control group, respective mean weight of 100.7 kg and 101.1 kg, and respective BMI of 36.7 and 36.9. Women comprised about 77% of participants in each group.
 

Endpoints met

The trial met its primary endpoint of a significantly greater reduction in pain at 18 months in the diet and exercise group as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and scored on a scale of 0 (no pain) to 20 (worst pain).

In an analysis adjusted for sex, BMI, and baseline values, there was a 32% reduction in pain scores from baseline in the active intervention arm versus 24% in the control arm (P = .02).

In all, 60.2% of participants assigned to diet and exercise had a minimum reduction in pain scores of at least 2 points at 18 months, compared with 49.7% of participants assigned to the attention control group. This translated into a relative risk for achieving at least a 2-point improvement with diet and exercise was 1.20 (P = .01).

Among participants who remained in the study for the entire 18 months, there were significant improvements in the diet and exercise group compared with controls in the prespecified secondary endpoints of weight change (–8 kg vs. –2 kg), waist circumference, WOMAC function, 6-minute walk distance, and mean Short Form–36 health-related quality of life subscale (P < .001 for all comparisons).

Dr. Messier acknowledged that the diagnosis of knee OA was based only on ACR clinical criteria and was not confirmed with imaging. In addition, offering patients the option of free meal replacement limited the pragmatic nature of the intervention.

He also noted that the 24% reduction in pain seen in the control group suggests that interacting with patients can improve clinical outcomes.
 

‘Tour de force’

In the question-and-answer session following Dr. Messier’s presentation, David T. Felson, MD, a rheumatologist at Boston Medical Center, called in and said the study was “a tour de force” and congratulated Dr. Messier and colleagues on “a lovely study.”

Richard Mark Kirkner/MDedge News

Dr. Felson asked whether the investigators had conducted a mediation analysis to determine what proportion of the improvement was attributable to weight loss, and whether patients assigned to exercise were sticking with it throughout the study.

Dr. Messier replied that they had not yet done a mediation analysis but were continuing to examine the data. Regarding the exercise question, he noted that “the adherence was over 80% for 6 months and over 70% for the whole 18 months, so they did a really nice job.”

In an interview, session moderator Anne Davidson, MBBS, director of the rheumatology program at Northwell Health in Manhasset, N.Y., commented that the investigators managed to accomplish a very challenging task.

“In terms of recruitment of patients with engagement of community facilities and quality of data, I would say that, as far as an osteoarthritis study goes, this was really a tremendous effort on the part of all people involved,” she said.

She noted that, while the WE-CAN program may work in North Carolina, there may be barriers to implementing it elsewhere, such as large suburban areas where some patients experience food insecurity and others have difficulty with transportation and access to treatment facilities.

“The question here that remains is, as Dr. Felson asked, what is the contribution of weight loss and what is the contribution of exercise? Because if it’s just weight loss, we have a whole lot of new things coming to help with that,” she said.

The WE-CAN study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Messier disclosed that GNC, a health food and nutrition chain, donated the meal replacements used by patients. Dr. Davidson reported no relevant conflicts of interest.

PHILADELPHIA – What works in the clinic can also work in community settings: Patients who are overweight or obese with knee osteoarthritis can find relief from pain through diet and exercise programs conducted in recreation centers, local gyms, fitness centers, and other places close to home, according to investigators in a pragmatic randomized trial.

The Weight Loss and Exercise for Communities With Arthritis in North Carolina (WE-CAN) study was modeled after the successful Intensive Diet and Exercise for Arthritis trial, which showed that adults randomized to 18 months of either a diet and exercise program or diet alone had more weight loss and larger reductions in levels of the inflammatory cytokine interleukin-6 than patients randomized to exercise alone, and that diet alone was associated with greater reductions in knee compressive force than exercise alone.