Study Overview

Objective: To evaluate whether the addition of the potent androgen-receptor inhibitor (ARA) darolutamide to the standard doublet androgen-deprivation therapy (ADT) and docetaxel in metastatic, hormone-sensitive prostate cancer (mHSPC) would increase survival.

Design: A randomized, double-blind, placebo-controlled, multicenter, phase 3 study. The results reported in this publication are from the prespecified interim analysis.

Intervention: Patients with mHSPC were randomly assigned to receive either darolutamide 600 mg twice daily or placebo. All patients received standard ADT with 6 cycles of docetaxel 75 mg/m² on day 1 every 21 days along with prednisone given within 6 weeks after randomization. Patients receiving luteinizing hormone–releasing hormone (LHRH) agonists as ADT were bridged with at least 4 weeks of first-generation antiandrogen therapy, which was discontinued before randomization. Treatments were continued until symptomatic disease progression, a change in neoplastic therapy, unacceptable toxicity, patient or physician decision, death, or nonadherence.

Setting and participants: Eligible patients included those newly diagnosed with mHSPC with metastases detected on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) and bone scan. Patients were excluded if they had regional lymph node–only involvement or if they had received more than 12 weeks of ADT before randomization. Between November 2016 and June 2018, 1306 patients (651 in the darolutamide group and 655 in the placebo group) were randomized in a 1:1 manner to receive darolutamide 600 mg twice daily or placebo in addition to ADT and docetaxel. Randomization was stratified based on the TNM staging system (M1a—nonregional lymph node–only metastasis, M1b—bone metastasis with or without lymph node, or M1c—bone metastases) as well as baseline alkaline phosphatase levels.

Main outcome measures: The primary end point for the study was overall survival. Other meaningful secondary end points included time to castration resistance, time to pain progression, time to first symptomatic skeletal event, symptomatic skeletal event-free survival, time to subsequent systemic antineoplastic therapy, time to worsening of disease-related physical symptoms, initiation of opioid therapy for ≥7 days, and safety.

Results: The baseline and demographic characteristics were well balanced between the 2 groups. Median age was 67 years. Nearly 80% of patients had bone metastasis, and approximately 17% had visceral metastasis. At the data cutoff date for the primary analysis, the median duration of therapy was 41 months for darolutamide compared with 16.7 months in the placebo group; 45.9% in the darolutamide group and 19.1% in the placebo group were receiving the allotted trial therapy at the time of the analysis. Six cycles of docetaxel were completed in approximately 85% of patients in both arms. Median overall survival follow-up was 43.7 months (darolutamide) and 42.4 months (placebo). A significant improvement in overall survival was observed in the darolutamide group. The risk of death was 32.5% lower in the darolutamide cohort than in the placebo cohort (hazard ratio [HR], 0.68; 95% CI, 0.57-0.80; P < .001). The overall survival at 4 years was 62.7% (95% CI, 58.7-66.7) in the darolutamide arm and 50.4% (95% CI, 46.3-54.6) in the placebo arm. The overall survival results remained favorable across most subgroups.

Darolutamide was associated with improvement in all key secondary endpoints. Time to castration-resistance was significantly longer in the darolutamide group (HR, 0.36; 95% CI, 0.30-0.42; P < .001). Time to pain progression was also significantly longer in the darolutamide group (HR, 0.79; 95% CI, 0.66-0.95; P = .01). Time to first symptomatic skeletal events (HR, 0.71; 95% CI, 0.54-0.94; P = .02) and time to initiation of subsequent systemic therapy (HR, 0.39; 95% CI, 0.33-0.46; P < .001) were also found to be longer in the darolutamide group.

Safety: The risk of grade 3 or higher adverse events was similar across the 2 groups. Most common adverse events were known toxic effects of docetaxel therapy and were highest during the initial period when both groups received this therapy. These side effects progressively decreased after the initial period. The most common grade 3 or 4 adverse event was neutropenia, and its frequency was similar between the darolutamide and placebo groups (33.7% and 34.2%, respectively). The most frequently reported adverse events were alopecia, neutropenia, fatigue, and anemia and were similar between the groups. Adverse events of special significance, including fatigue, falls, fractures, and cardiovascular events, were also similar between the 2 groups. Adverse events causing deaths in each arm were low and similar (4.1% in the darolutamide group and 4.0% in the placebo group). The rates of discontinuation of darolutamide or placebo were similar (13.5% and 10.6%, respectively).

Conclusion: Among patients with mHSPC, overall survival was significantly longer among patients who received darolutamide plus ADT and docetaxel than among those who received ADT and docetaxel alone. This was observed despite a high percentage of patients in the placebo group receiving subsequent systemic therapy at the time of progression. The survival benefit of darolutamide was maintained across most subgroups. An improvement was also observed in the darolutamide arm in terms of key secondary end points. The adverse events were similar across the groups and were consistent with known safety profiles of ADT and docetaxel, and no new safety signals were identified in this trial.

Commentary

The results of the current study add to the body of literature supporting multi-agent systemic therapy in newly diagnosed mHSPC. Prior phase 3 trials of combination therapy using androgen-receptor pathway inhibitors, ADT, and docetaxel have shown conflicting results. The results from the previously reported PEACE-1 study showed improved overall survival among patients who received abiraterone with ADT and docetaxel as compared with those who received ADT and docetaxel alone.¹ However, as noted by the authors, the subgroup of patients in the ENZAMET trial who received docetaxel, enzalutamide, and ADT did not appear to have a survival advantage compared with those who received ADT and docetaxel alone.² The results from the current ARASENS trial provide compelling evidence in a population of prospectively randomized patients that combination therapy with darolutamide, docetaxel, and ADT improves overall survival in men with mHSPC. The survival advantage was maintained across subgroups analyzed in this study. Improvements were observed in regards to several key secondary end points with use of darolutamide. This benefit was maintained despite many patients receiving subsequent therapy at the time of progression. Importantly, there did not appear to be a significant increase in toxicity with triplet therapy. However, it is important to note that this cohort of patients appeared largely asymptomatic at the time of enrollment, with 70% of patients having an Eastern Cooperative Oncology Group performance status of 0.

Additionally, the average age in this study was 67 years, with only about 15% of the population being older than 75 years. In the reported subgroup analysis, those older than 75 years appeared to derive a similar benefit in overall survival, however. Whether triplet therapy should be universally adopted in all patients remains unclear. For example, there is a subset of patients with mHSPC with favorable- risk disease (ie, those with recurrent metastatic disease, node-only disease). In this population, the risk-benefit analysis is less clear, and whether these patients should receive this combination is not certain. Nevertheless, the results of this well-designed study are compelling and certainly represent a potential new standard treatment option for men with mHSPC. One of the strengths of this study was its large sample size that allowed for vigorous statistical analysis to evaluate the efficacy of darolutamide in combination with ADT and docetaxel.

Application for Clinical Practice

The ARASENS study provides convincing evidence that in men with mHSPC, the addition of darolutamide to docetaxel and ADT improves overall survival. This combination appeared to be well tolerated, with no evidence of increased toxicity noted. Certainly, this combination represents a potential new standard treatment option in this population; however, further understanding of which subgroups of men benefit from enhanced therapy is needed to aid in proper patient selection. 

—Santosh Kagathur, MD, and Daniel Isaac, DO, MS
Michigan State University, East Lansing, MI

Study Overview

Objective: To evaluate whether the addition of the potent androgen-receptor inhibitor (ARA) darolutamide to the standard doublet androgen-deprivation therapy (ADT) and docetaxel in metastatic, hormone-sensitive prostate cancer (mHSPC) would increase survival.

Design: A randomized, double-blind, placebo-controlled, multicenter, phase 3 study. The results reported in this publication are from the prespecified interim analysis.

Intervention: Patients with mHSPC were randomly assigned to receive either darolutamide 600 mg twice daily or placebo. All patients received standard ADT with 6 cycles of docetaxel 75 mg/m² on day 1 every 21 days along with prednisone given within 6 weeks after randomization. Patients receiving luteinizing hormone–releasing hormone (LHRH) agonists as ADT were bridged with at least 4 weeks of first-generation antiandrogen therapy, which was discontinued before randomization. Treatments were continued until symptomatic disease progression, a change in neoplastic therapy, unacceptable toxicity, patient or physician decision, death, or nonadherence.

Setting and participants: Eligible patients included those newly diagnosed with mHSPC with metastases detected on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) and bone scan. Patients were excluded if they had regional lymph node–only involvement or if they had received more than 12 weeks of ADT before randomization. Between November 2016 and June 2018, 1306 patients (651 in the darolutamide group and 655 in the placebo group) were randomized in a 1:1 manner to receive darolutamide 600 mg twice daily or placebo in addition to ADT and docetaxel. Randomization was stratified based on the TNM staging system (M1a—nonregional lymph node–only metastasis, M1b—bone metastasis with or without lymph node, or M1c—bone metastases) as well as baseline alkaline phosphatase levels.

Main outcome measures: The primary end point for the study was overall survival. Other meaningful secondary end points included time to castration resistance, time to pain progression, time to first symptomatic skeletal event, symptomatic skeletal event-free survival, time to subsequent systemic antineoplastic therapy, time to worsening of disease-related physical symptoms, initiation of opioid therapy for ≥7 days, and safety.

Results: The baseline and demographic characteristics were well balanced between the 2 groups. Median age was 67 years. Nearly 80% of patients had bone metastasis, and approximately 17% had visceral metastasis. At the data cutoff date for the primary analysis, the median duration of therapy was 41 months for darolutamide compared with 16.7 months in the placebo group; 45.9% in the darolutamide group and 19.1% in the placebo group were receiving the allotted trial therapy at the time of the analysis. Six cycles of docetaxel were completed in approximately 85% of patients in both arms. Median overall survival follow-up was 43.7 months (darolutamide) and 42.4 months (placebo). A significant improvement in overall survival was observed in the darolutamide group. The risk of death was 32.5% lower in the darolutamide cohort than in the placebo cohort (hazard ratio [HR], 0.68; 95% CI, 0.57-0.80; P < .001). The overall survival at 4 years was 62.7% (95% CI, 58.7-66.7) in the darolutamide arm and 50.4% (95% CI, 46.3-54.6) in the placebo arm. The overall survival results remained favorable across most subgroups.

Darolutamide was associated with improvement in all key secondary endpoints. Time to castration-resistance was significantly longer in the darolutamide group (HR, 0.36; 95% CI, 0.30-0.42; P < .001). Time to pain progression was also significantly longer in the darolutamide group (HR, 0.79; 95% CI, 0.66-0.95; P = .01). Time to first symptomatic skeletal events (HR, 0.71; 95% CI, 0.54-0.94; P = .02) and time to initiation of subsequent systemic therapy (HR, 0.39; 95% CI, 0.33-0.46; P < .001) were also found to be longer in the darolutamide group.

Safety: The risk of grade 3 or higher adverse events was similar across the 2 groups. Most common adverse events were known toxic effects of docetaxel therapy and were highest during the initial period when both groups received this therapy. These side effects progressively decreased after the initial period. The most common grade 3 or 4 adverse event was neutropenia, and its frequency was similar between the darolutamide and placebo groups (33.7% and 34.2%, respectively). The most frequently reported adverse events were alopecia, neutropenia, fatigue, and anemia and were similar between the groups. Adverse events of special significance, including fatigue, falls, fractures, and cardiovascular events, were also similar between the 2 groups. Adverse events causing deaths in each arm were low and similar (4.1% in the darolutamide group and 4.0% in the placebo group). The rates of discontinuation of darolutamide or placebo were similar (13.5% and 10.6%, respectively).

Conclusion: Among patients with mHSPC, overall survival was significantly longer among patients who received darolutamide plus ADT and docetaxel than among those who received ADT and docetaxel alone. This was observed despite a high percentage of patients in the placebo group receiving subsequent systemic therapy at the time of progression. The survival benefit of darolutamide was maintained across most subgroups. An improvement was also observed in the darolutamide arm in terms of key secondary end points. The adverse events were similar across the groups and were consistent with known safety profiles of ADT and docetaxel, and no new safety signals were identified in this trial.

Commentary

The results of the current study add to the body of literature supporting multi-agent systemic therapy in newly diagnosed mHSPC. Prior phase 3 trials of combination therapy using androgen-receptor pathway inhibitors, ADT, and docetaxel have shown conflicting results. The results from the previously reported PEACE-1 study showed improved overall survival among patients who received abiraterone with ADT and docetaxel as compared with those who received ADT and docetaxel alone.¹ However, as noted by the authors, the subgroup of patients in the ENZAMET trial who received docetaxel, enzalutamide, and ADT did not appear to have a survival advantage compared with those who received ADT and docetaxel alone.² The results from the current ARASENS trial provide compelling evidence in a population of prospectively randomized patients that combination therapy with darolutamide, docetaxel, and ADT improves overall survival in men with mHSPC. The survival advantage was maintained across subgroups analyzed in this study. Improvements were observed in regards to several key secondary end points with use of darolutamide. This benefit was maintained despite many patients receiving subsequent therapy at the time of progression. Importantly, there did not appear to be a significant increase in toxicity with triplet therapy. However, it is important to note that this cohort of patients appeared largely asymptomatic at the time of enrollment, with 70% of patients having an Eastern Cooperative Oncology Group performance status of 0.

Additionally, the average age in this study was 67 years, with only about 15% of the population being older than 75 years. In the reported subgroup analysis, those older than 75 years appeared to derive a similar benefit in overall survival, however. Whether triplet therapy should be universally adopted in all patients remains unclear. For example, there is a subset of patients with mHSPC with favorable- risk disease (ie, those with recurrent metastatic disease, node-only disease). In this population, the risk-benefit analysis is less clear, and whether these patients should receive this combination is not certain. Nevertheless, the results of this well-designed study are compelling and certainly represent a potential new standard treatment option for men with mHSPC. One of the strengths of this study was its large sample size that allowed for vigorous statistical analysis to evaluate the efficacy of darolutamide in combination with ADT and docetaxel.

Application for Clinical Practice

The ARASENS study provides convincing evidence that in men with mHSPC, the addition of darolutamide to docetaxel and ADT improves overall survival. This combination appeared to be well tolerated, with no evidence of increased toxicity noted. Certainly, this combination represents a potential new standard treatment option in this population; however, further understanding of which subgroups of men benefit from enhanced therapy is needed to aid in proper patient selection. 

—Santosh Kagathur, MD, and Daniel Isaac, DO, MS
Michigan State University, East Lansing, MI

Study Overview

Objective: To evaluate whether the addition of the potent androgen-receptor inhibitor (ARA) darolutamide to the standard doublet androgen-deprivation therapy (ADT) and docetaxel in metastatic, hormone-sensitive prostate cancer (mHSPC) would increase survival.

Design: A randomized, double-blind, placebo-controlled, multicenter, phase 3 study. The results reported in this publication are from the prespecified interim analysis.

Intervention: Patients with mHSPC were randomly assigned to receive either darolutamide 600 mg twice daily or placebo. All patients received standard ADT with 6 cycles of docetaxel 75 mg/m² on day 1 every 21 days along with prednisone given within 6 weeks after randomization. Patients receiving luteinizing hormone–releasing hormone (LHRH) agonists as ADT were bridged with at least 4 weeks of first-generation antiandrogen therapy, which was discontinued before randomization. Treatments were continued until symptomatic disease progression, a change in neoplastic therapy, unacceptable toxicity, patient or physician decision, death, or nonadherence.

Setting and participants: Eligible patients included those newly diagnosed with mHSPC with metastases detected on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) and bone scan. Patients were excluded if they had regional lymph node–only involvement or if they had received more than 12 weeks of ADT before randomization. Between November 2016 and June 2018, 1306 patients (651 in the darolutamide group and 655 in the placebo group) were randomized in a 1:1 manner to receive darolutamide 600 mg twice daily or placebo in addition to ADT and docetaxel. Randomization was stratified based on the TNM staging system (M1a—nonregional lymph node–only metastasis, M1b—bone metastasis with or without lymph node, or M1c—bone metastases) as well as baseline alkaline phosphatase levels.

Main outcome measures: The primary end point for the study was overall survival. Other meaningful secondary end points included time to castration resistance, time to pain progression, time to first symptomatic skeletal event, symptomatic skeletal event-free survival, time to subsequent systemic antineoplastic therapy, time to worsening of disease-related physical symptoms, initiation of opioid therapy for ≥7 days, and safety.

Results: The baseline and demographic characteristics were well balanced between the 2 groups. Median age was 67 years. Nearly 80% of patients had bone metastasis, and approximately 17% had visceral metastasis. At the data cutoff date for the primary analysis, the median duration of therapy was 41 months for darolutamide compared with 16.7 months in the placebo group; 45.9% in the darolutamide group and 19.1% in the placebo group were receiving the allotted trial therapy at the time of the analysis. Six cycles of docetaxel were completed in approximately 85% of patients in both arms. Median overall survival follow-up was 43.7 months (darolutamide) and 42.4 months (placebo). A significant improvement in overall survival was observed in the darolutamide group. The risk of death was 32.5% lower in the darolutamide cohort than in the placebo cohort (hazard ratio [HR], 0.68; 95% CI, 0.57-0.80; P < .001). The overall survival at 4 years was 62.7% (95% CI, 58.7-66.7) in the darolutamide arm and 50.4% (95% CI, 46.3-54.6) in the placebo arm. The overall survival results remained favorable across most subgroups.

Darolutamide was associated with improvement in all key secondary endpoints. Time to castration-resistance was significantly longer in the darolutamide group (HR, 0.36; 95% CI, 0.30-0.42; P < .001). Time to pain progression was also significantly longer in the darolutamide group (HR, 0.79; 95% CI, 0.66-0.95; P = .01). Time to first symptomatic skeletal events (HR, 0.71; 95% CI, 0.54-0.94; P = .02) and time to initiation of subsequent systemic therapy (HR, 0.39; 95% CI, 0.33-0.46; P < .001) were also found to be longer in the darolutamide group.

Safety: The risk of grade 3 or higher adverse events was similar across the 2 groups. Most common adverse events were known toxic effects of docetaxel therapy and were highest during the initial period when both groups received this therapy. These side effects progressively decreased after the initial period. The most common grade 3 or 4 adverse event was neutropenia, and its frequency was similar between the darolutamide and placebo groups (33.7% and 34.2%, respectively). The most frequently reported adverse events were alopecia, neutropenia, fatigue, and anemia and were similar between the groups. Adverse events of special significance, including fatigue, falls, fractures, and cardiovascular events, were also similar between the 2 groups. Adverse events causing deaths in each arm were low and similar (4.1% in the darolutamide group and 4.0% in the placebo group). The rates of discontinuation of darolutamide or placebo were similar (13.5% and 10.6%, respectively).

Conclusion: Among patients with mHSPC, overall survival was significantly longer among patients who received darolutamide plus ADT and docetaxel than among those who received ADT and docetaxel alone. This was observed despite a high percentage of patients in the placebo group receiving subsequent systemic therapy at the time of progression. The survival benefit of darolutamide was maintained across most subgroups. An improvement was also observed in the darolutamide arm in terms of key secondary end points. The adverse events were similar across the groups and were consistent with known safety profiles of ADT and docetaxel, and no new safety signals were identified in this trial.

Commentary

The results of the current study add to the body of literature supporting multi-agent systemic therapy in newly diagnosed mHSPC. Prior phase 3 trials of combination therapy using androgen-receptor pathway inhibitors, ADT, and docetaxel have shown conflicting results. The results from the previously reported PEACE-1 study showed improved overall survival among patients who received abiraterone with ADT and docetaxel as compared with those who received ADT and docetaxel alone.¹ However, as noted by the authors, the subgroup of patients in the ENZAMET trial who received docetaxel, enzalutamide, and ADT did not appear to have a survival advantage compared with those who received ADT and docetaxel alone.² The results from the current ARASENS trial provide compelling evidence in a population of prospectively randomized patients that combination therapy with darolutamide, docetaxel, and ADT improves overall survival in men with mHSPC. The survival advantage was maintained across subgroups analyzed in this study. Improvements were observed in regards to several key secondary end points with use of darolutamide. This benefit was maintained despite many patients receiving subsequent therapy at the time of progression. Importantly, there did not appear to be a significant increase in toxicity with triplet therapy. However, it is important to note that this cohort of patients appeared largely asymptomatic at the time of enrollment, with 70% of patients having an Eastern Cooperative Oncology Group performance status of 0.

Additionally, the average age in this study was 67 years, with only about 15% of the population being older than 75 years. In the reported subgroup analysis, those older than 75 years appeared to derive a similar benefit in overall survival, however. Whether triplet therapy should be universally adopted in all patients remains unclear. For example, there is a subset of patients with mHSPC with favorable- risk disease (ie, those with recurrent metastatic disease, node-only disease). In this population, the risk-benefit analysis is less clear, and whether these patients should receive this combination is not certain. Nevertheless, the results of this well-designed study are compelling and certainly represent a potential new standard treatment option for men with mHSPC. One of the strengths of this study was its large sample size that allowed for vigorous statistical analysis to evaluate the efficacy of darolutamide in combination with ADT and docetaxel.

Application for Clinical Practice

The ARASENS study provides convincing evidence that in men with mHSPC, the addition of darolutamide to docetaxel and ADT improves overall survival. This combination appeared to be well tolerated, with no evidence of increased toxicity noted. Certainly, this combination represents a potential new standard treatment option in this population; however, further understanding of which subgroups of men benefit from enhanced therapy is needed to aid in proper patient selection. 

—Santosh Kagathur, MD, and Daniel Isaac, DO, MS
Michigan State University, East Lansing, MI

Study 1 Overview (SCOT-HEART Investigators)

Objective: To assess cardiovascular mortality and nonfatal myocardial infarction at 5 years in patients with stable chest pain referred to cardiology clinic for management with either standard care plus computed tomography angiography (CTA) or standard care alone.

Design: Multicenter, randomized, open-label prospective study.

Setting and participants: A total of 4146 patients with stable chest pain were randomized to standard care or standard care plus CTA at 12 centers across Scotland and were followed for 5 years.

Main outcome measures: The primary end point was a composite of death from coronary heart disease or nonfatal myocardial infarction. Main secondary end points were nonfatal myocardial infarction, nonfatal stroke, and frequency of invasive coronary angiography (ICA) and coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting.

Main results: The primary outcome including the composite of cardiovascular death or nonfatal myocardial infarction was lower in the CTA group than in the standard-care group at 2.3% (48 of 2073 patients) vs 3.9% (81 of 2073 patients), respectively (hazard ratio, 0.59; 95% CI, 0.41-0.84; P = .004). Although there was a higher rate of ICA and coronary revascularization in the CTA group than in the standard-care group in the first few months of follow-up, the overall rates were similar at 5 years, with ICA performed in 491 patients and 502 patients in the CTA vs standard-care groups, respectively (hazard ratio, 1.00; 95% CI, 0.88-1.13). Similarly, coronary revascularization was performed in 279 patients in the CTA group and in 267 patients in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91-1.27). There were, however, more preventive therapies initiated in patients in the CTA group than in the standard-care group (odds ratio, 1.40; 95% CI, 1.19-1.65).

Conclusion: In patients with stable chest pain, the use of CTA in addition to standard care resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years; the main contributor to this outcome was a reduced nonfatal myocardial infarction rate. There was no difference in the rate of coronary angiography or coronary revascularization between the 2 groups at 5 years.

Study 2 Overview (DISCHARGE Trial Group)

Objective: To compare the effectiveness of computed tomography (CT) with ICA as a diagnostic tool in patients with stable chest pain and intermediate pretest probability of coronary artery disease (CAD).

Design: Multicenter, randomized, assessor-blinded pragmatic prospective study.

Setting and participants: A total of 3667 patients with stable chest pain and intermediate pretest probability of CAD were enrolled at 26 centers and randomized into CT or ICA groups. Only 3561 patients were included in the modified intention-to-treat analysis, with 1808 patients and 1753 patients in the CT and ICA groups, respectively.

Main outcome measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke over 3.5 years. The main secondary outcomes were major procedure-related complications and patient-reported angina pectoris during the last 4 weeks of follow up.

Main results: The primary outcome occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 patients (3.0%) in the ICA group (hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). The secondary outcomes showed that major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 patients (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13-0.55). Rates of patient-reported angina in the final 4 weeks of follow-up were 8.8% in the CT group and 7.5% in the ICA group (odds ratio, 1.17; 95% CI, 0.92-1.48).

Conclusion: Risk of major adverse cardiovascular events from the primary outcome were similar in both the CT and ICA groups among patients with stable chest pain and intermediate pretest probability of CAD. Patients referred for CT had a lower rate of coronary angiography leading to fewer major procedure-related complications in these patients than in those referred for ICA.

Evaluation and treatment of obstructive atherosclerosis is an important part of clinical care in patients presenting with angina symptoms.¹ Thus, the initial investigation for patients with suspected obstructive CAD includes ruling out acute coronary syndrome and assessing quality of life.¹ The diagnostic test should be tailored to the pretest probability for the diagnosis of obstructive CAD.²

In the United States, stress testing traditionally has been used for the initial assessment in patients with suspected CAD,³ but recently CTA has been utilized more frequently for this purpose. Compared to a stress test, which often helps identify and assess ischemia, CTA can provide anatomical assessment, with higher sensitivity to identify CAD.⁴ Furthermore, it can distinguish nonobstructive plaques that can be challenging to identify with stress test alone.

Whether CTA is superior to stress testing as the initial assessment for CAD has been debated. The randomized PROMISE trial compared patients with stable angina who underwent functional stress testing or CTA as an initial strategy.⁵ They reported a similar outcome between the 2 groups at a median follow-up of 2 years. However, in the original SCOT-HEART trial (CT coronary angiography in patients with suspected angina due to coronary heart disease), which was published in the same year as the PROMISE trial, the patients who underwent initial assessment with CTA had a numerically lower composite end point of cardiac death and myocardial infarction at a median follow-up of 1.7 years (1.3% vs 2.0%, P = .053).⁶

Given this result, the SCOT-HEART investigators extended the follow-up to evaluate the composite end point of death from coronary heart disease or nonfatal myocardial infarction at 5 years.⁷ This trial enrolled patients who were initially referred to a cardiology clinic for evaluation of chest pain, and they were randomized to standard care plus CTA or standard care alone. At a median duration of 4.8 years, the primary outcome was lower in the CTA group (2.3%, 48 patients) than in the standard-care group (3.9%, 81 patients) (hazard ratio, 0.58; 95% CI, 0.41-0.84; P = .004). Both groups had similar rates of invasive coronary angiography and had similar coronary revascularization rates.

It is hypothesized that this lower rate of nonfatal myocardial infarction in patients with CTA plus standard care is associated with a higher rate of preventive therapies initiated in patients in the CTA-plus-standard-care group compared to standard care alone. However, the difference in the standard-care group should be noted when compared to the PROMISE trial. In the PROMISE trial, the comparator group had predominantly stress imaging (either nuclear stress test or echocardiography), while in the SCOT-HEART trial, the group had predominantly stress electrocardiogram (ECG), and only 10% of the patients underwent stress imaging. It is possible the difference seen in the rate of nonfatal myocardial infarction was due to suboptimal diagnosis of CAD with stress ECG, which has lower sensitivity compared to stress imaging.

The DISCHARGE trial investigated the effectiveness of CTA vs ICA as the initial diagnostic test in the management of patients with stable chest pain and an intermediate pretest probability of obstructive CAD.⁸ At 3.5 years of follow-up, the primary composite of cardiovascular death, myocardial infarction, or stroke was similar in both groups (2.1% vs 3.0; hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). Importantly, as fewer patients underwent ICA, the risk of procedure-related complication was lower in the CTA group than in the ICA group. However, it is important to note that only 25% of the patients diagnosed with obstructive CAD had greater than 50% vessel stenosis, which raises the question of whether an initial invasive strategy is appropriate for this population.

The strengths of these 2 studies include the large number of patients enrolled along with adequate follow-up, 5 years in the SCOT-HEART trial and 3.5 years in the DISCHARGE trial. The 2 studies overall suggest the usefulness of CTA for assessment of CAD. However, the control groups were very different in these 2 trials. In the SCOT-HEART study, the comparator group was primarily assessed by stress ECG, while in the DISCHARGE study, the comparator group was primary assessed by ICA. In the PROMISE trial, the composite end point of death, myocardial infarction, hospitalization for unstable angina, or major procedural complication was similar when the strategy of initial CTA was compared to functional testing with imaging (exercise ECG, nuclear stress testing, or echocardiography).⁵ Thus, clinical assessment is still needed when clinicians are selecting the appropriate diagnostic test for patients with suspected CAD. The most recent guidelines give similar recommendations for CTA compared to stress imaging.⁹ Whether further improvement in CTA acquisition or the addition of CT fractional flow reserve can further improve outcomes requires additional study.

Applications for Clinical Practice and System Implementation

In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful in diagnosis compared to stress ECG and in reducing utilization of low-yield ICA. Whether CTA is more useful compared to the other noninvasive stress imaging modalities in this population requires further study.

Practice Points

• In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful compared to stress ECG.
• Use of CTA can potentially reduce the use of low-yield coronary angiography.

–Thai Nguyen, MD, Albert Chan, MD, Taishi Hirai, MD
University of Missouri, Columbia, MO

Study 1 Overview (SCOT-HEART Investigators)

Objective: To assess cardiovascular mortality and nonfatal myocardial infarction at 5 years in patients with stable chest pain referred to cardiology clinic for management with either standard care plus computed tomography angiography (CTA) or standard care alone.

Design: Multicenter, randomized, open-label prospective study.

Setting and participants: A total of 4146 patients with stable chest pain were randomized to standard care or standard care plus CTA at 12 centers across Scotland and were followed for 5 years.

Main outcome measures: The primary end point was a composite of death from coronary heart disease or nonfatal myocardial infarction. Main secondary end points were nonfatal myocardial infarction, nonfatal stroke, and frequency of invasive coronary angiography (ICA) and coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting.

Main results: The primary outcome including the composite of cardiovascular death or nonfatal myocardial infarction was lower in the CTA group than in the standard-care group at 2.3% (48 of 2073 patients) vs 3.9% (81 of 2073 patients), respectively (hazard ratio, 0.59; 95% CI, 0.41-0.84; P = .004). Although there was a higher rate of ICA and coronary revascularization in the CTA group than in the standard-care group in the first few months of follow-up, the overall rates were similar at 5 years, with ICA performed in 491 patients and 502 patients in the CTA vs standard-care groups, respectively (hazard ratio, 1.00; 95% CI, 0.88-1.13). Similarly, coronary revascularization was performed in 279 patients in the CTA group and in 267 patients in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91-1.27). There were, however, more preventive therapies initiated in patients in the CTA group than in the standard-care group (odds ratio, 1.40; 95% CI, 1.19-1.65).

Conclusion: In patients with stable chest pain, the use of CTA in addition to standard care resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years; the main contributor to this outcome was a reduced nonfatal myocardial infarction rate. There was no difference in the rate of coronary angiography or coronary revascularization between the 2 groups at 5 years.

Study 2 Overview (DISCHARGE Trial Group)

Objective: To compare the effectiveness of computed tomography (CT) with ICA as a diagnostic tool in patients with stable chest pain and intermediate pretest probability of coronary artery disease (CAD).

Design: Multicenter, randomized, assessor-blinded pragmatic prospective study.

Setting and participants: A total of 3667 patients with stable chest pain and intermediate pretest probability of CAD were enrolled at 26 centers and randomized into CT or ICA groups. Only 3561 patients were included in the modified intention-to-treat analysis, with 1808 patients and 1753 patients in the CT and ICA groups, respectively.

Main outcome measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke over 3.5 years. The main secondary outcomes were major procedure-related complications and patient-reported angina pectoris during the last 4 weeks of follow up.

Main results: The primary outcome occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 patients (3.0%) in the ICA group (hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). The secondary outcomes showed that major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 patients (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13-0.55). Rates of patient-reported angina in the final 4 weeks of follow-up were 8.8% in the CT group and 7.5% in the ICA group (odds ratio, 1.17; 95% CI, 0.92-1.48).

Conclusion: Risk of major adverse cardiovascular events from the primary outcome were similar in both the CT and ICA groups among patients with stable chest pain and intermediate pretest probability of CAD. Patients referred for CT had a lower rate of coronary angiography leading to fewer major procedure-related complications in these patients than in those referred for ICA.

Evaluation and treatment of obstructive atherosclerosis is an important part of clinical care in patients presenting with angina symptoms.¹ Thus, the initial investigation for patients with suspected obstructive CAD includes ruling out acute coronary syndrome and assessing quality of life.¹ The diagnostic test should be tailored to the pretest probability for the diagnosis of obstructive CAD.²

In the United States, stress testing traditionally has been used for the initial assessment in patients with suspected CAD,³ but recently CTA has been utilized more frequently for this purpose. Compared to a stress test, which often helps identify and assess ischemia, CTA can provide anatomical assessment, with higher sensitivity to identify CAD.⁴ Furthermore, it can distinguish nonobstructive plaques that can be challenging to identify with stress test alone.

Whether CTA is superior to stress testing as the initial assessment for CAD has been debated. The randomized PROMISE trial compared patients with stable angina who underwent functional stress testing or CTA as an initial strategy.⁵ They reported a similar outcome between the 2 groups at a median follow-up of 2 years. However, in the original SCOT-HEART trial (CT coronary angiography in patients with suspected angina due to coronary heart disease), which was published in the same year as the PROMISE trial, the patients who underwent initial assessment with CTA had a numerically lower composite end point of cardiac death and myocardial infarction at a median follow-up of 1.7 years (1.3% vs 2.0%, P = .053).⁶

Given this result, the SCOT-HEART investigators extended the follow-up to evaluate the composite end point of death from coronary heart disease or nonfatal myocardial infarction at 5 years.⁷ This trial enrolled patients who were initially referred to a cardiology clinic for evaluation of chest pain, and they were randomized to standard care plus CTA or standard care alone. At a median duration of 4.8 years, the primary outcome was lower in the CTA group (2.3%, 48 patients) than in the standard-care group (3.9%, 81 patients) (hazard ratio, 0.58; 95% CI, 0.41-0.84; P = .004). Both groups had similar rates of invasive coronary angiography and had similar coronary revascularization rates.

It is hypothesized that this lower rate of nonfatal myocardial infarction in patients with CTA plus standard care is associated with a higher rate of preventive therapies initiated in patients in the CTA-plus-standard-care group compared to standard care alone. However, the difference in the standard-care group should be noted when compared to the PROMISE trial. In the PROMISE trial, the comparator group had predominantly stress imaging (either nuclear stress test or echocardiography), while in the SCOT-HEART trial, the group had predominantly stress electrocardiogram (ECG), and only 10% of the patients underwent stress imaging. It is possible the difference seen in the rate of nonfatal myocardial infarction was due to suboptimal diagnosis of CAD with stress ECG, which has lower sensitivity compared to stress imaging.

The DISCHARGE trial investigated the effectiveness of CTA vs ICA as the initial diagnostic test in the management of patients with stable chest pain and an intermediate pretest probability of obstructive CAD.⁸ At 3.5 years of follow-up, the primary composite of cardiovascular death, myocardial infarction, or stroke was similar in both groups (2.1% vs 3.0; hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). Importantly, as fewer patients underwent ICA, the risk of procedure-related complication was lower in the CTA group than in the ICA group. However, it is important to note that only 25% of the patients diagnosed with obstructive CAD had greater than 50% vessel stenosis, which raises the question of whether an initial invasive strategy is appropriate for this population.

The strengths of these 2 studies include the large number of patients enrolled along with adequate follow-up, 5 years in the SCOT-HEART trial and 3.5 years in the DISCHARGE trial. The 2 studies overall suggest the usefulness of CTA for assessment of CAD. However, the control groups were very different in these 2 trials. In the SCOT-HEART study, the comparator group was primarily assessed by stress ECG, while in the DISCHARGE study, the comparator group was primary assessed by ICA. In the PROMISE trial, the composite end point of death, myocardial infarction, hospitalization for unstable angina, or major procedural complication was similar when the strategy of initial CTA was compared to functional testing with imaging (exercise ECG, nuclear stress testing, or echocardiography).⁵ Thus, clinical assessment is still needed when clinicians are selecting the appropriate diagnostic test for patients with suspected CAD. The most recent guidelines give similar recommendations for CTA compared to stress imaging.⁹ Whether further improvement in CTA acquisition or the addition of CT fractional flow reserve can further improve outcomes requires additional study.

Applications for Clinical Practice and System Implementation

In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful in diagnosis compared to stress ECG and in reducing utilization of low-yield ICA. Whether CTA is more useful compared to the other noninvasive stress imaging modalities in this population requires further study.

Practice Points

• In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful compared to stress ECG.
• Use of CTA can potentially reduce the use of low-yield coronary angiography.

–Thai Nguyen, MD, Albert Chan, MD, Taishi Hirai, MD
University of Missouri, Columbia, MO

Study 1 Overview (SCOT-HEART Investigators)

Objective: To assess cardiovascular mortality and nonfatal myocardial infarction at 5 years in patients with stable chest pain referred to cardiology clinic for management with either standard care plus computed tomography angiography (CTA) or standard care alone.

Design: Multicenter, randomized, open-label prospective study.

Setting and participants: A total of 4146 patients with stable chest pain were randomized to standard care or standard care plus CTA at 12 centers across Scotland and were followed for 5 years.

Main outcome measures: The primary end point was a composite of death from coronary heart disease or nonfatal myocardial infarction. Main secondary end points were nonfatal myocardial infarction, nonfatal stroke, and frequency of invasive coronary angiography (ICA) and coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting.

Main results: The primary outcome including the composite of cardiovascular death or nonfatal myocardial infarction was lower in the CTA group than in the standard-care group at 2.3% (48 of 2073 patients) vs 3.9% (81 of 2073 patients), respectively (hazard ratio, 0.59; 95% CI, 0.41-0.84; P = .004). Although there was a higher rate of ICA and coronary revascularization in the CTA group than in the standard-care group in the first few months of follow-up, the overall rates were similar at 5 years, with ICA performed in 491 patients and 502 patients in the CTA vs standard-care groups, respectively (hazard ratio, 1.00; 95% CI, 0.88-1.13). Similarly, coronary revascularization was performed in 279 patients in the CTA group and in 267 patients in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91-1.27). There were, however, more preventive therapies initiated in patients in the CTA group than in the standard-care group (odds ratio, 1.40; 95% CI, 1.19-1.65).

Conclusion: In patients with stable chest pain, the use of CTA in addition to standard care resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years; the main contributor to this outcome was a reduced nonfatal myocardial infarction rate. There was no difference in the rate of coronary angiography or coronary revascularization between the 2 groups at 5 years.

Study 2 Overview (DISCHARGE Trial Group)

Objective: To compare the effectiveness of computed tomography (CT) with ICA as a diagnostic tool in patients with stable chest pain and intermediate pretest probability of coronary artery disease (CAD).

Design: Multicenter, randomized, assessor-blinded pragmatic prospective study.

Setting and participants: A total of 3667 patients with stable chest pain and intermediate pretest probability of CAD were enrolled at 26 centers and randomized into CT or ICA groups. Only 3561 patients were included in the modified intention-to-treat analysis, with 1808 patients and 1753 patients in the CT and ICA groups, respectively.

Main outcome measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke over 3.5 years. The main secondary outcomes were major procedure-related complications and patient-reported angina pectoris during the last 4 weeks of follow up.

Main results: The primary outcome occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 patients (3.0%) in the ICA group (hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). The secondary outcomes showed that major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 patients (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13-0.55). Rates of patient-reported angina in the final 4 weeks of follow-up were 8.8% in the CT group and 7.5% in the ICA group (odds ratio, 1.17; 95% CI, 0.92-1.48).

Conclusion: Risk of major adverse cardiovascular events from the primary outcome were similar in both the CT and ICA groups among patients with stable chest pain and intermediate pretest probability of CAD. Patients referred for CT had a lower rate of coronary angiography leading to fewer major procedure-related complications in these patients than in those referred for ICA.

Evaluation and treatment of obstructive atherosclerosis is an important part of clinical care in patients presenting with angina symptoms.¹ Thus, the initial investigation for patients with suspected obstructive CAD includes ruling out acute coronary syndrome and assessing quality of life.¹ The diagnostic test should be tailored to the pretest probability for the diagnosis of obstructive CAD.²

In the United States, stress testing traditionally has been used for the initial assessment in patients with suspected CAD,³ but recently CTA has been utilized more frequently for this purpose. Compared to a stress test, which often helps identify and assess ischemia, CTA can provide anatomical assessment, with higher sensitivity to identify CAD.⁴ Furthermore, it can distinguish nonobstructive plaques that can be challenging to identify with stress test alone.

Whether CTA is superior to stress testing as the initial assessment for CAD has been debated. The randomized PROMISE trial compared patients with stable angina who underwent functional stress testing or CTA as an initial strategy.⁵ They reported a similar outcome between the 2 groups at a median follow-up of 2 years. However, in the original SCOT-HEART trial (CT coronary angiography in patients with suspected angina due to coronary heart disease), which was published in the same year as the PROMISE trial, the patients who underwent initial assessment with CTA had a numerically lower composite end point of cardiac death and myocardial infarction at a median follow-up of 1.7 years (1.3% vs 2.0%, P = .053).⁶

Given this result, the SCOT-HEART investigators extended the follow-up to evaluate the composite end point of death from coronary heart disease or nonfatal myocardial infarction at 5 years.⁷ This trial enrolled patients who were initially referred to a cardiology clinic for evaluation of chest pain, and they were randomized to standard care plus CTA or standard care alone. At a median duration of 4.8 years, the primary outcome was lower in the CTA group (2.3%, 48 patients) than in the standard-care group (3.9%, 81 patients) (hazard ratio, 0.58; 95% CI, 0.41-0.84; P = .004). Both groups had similar rates of invasive coronary angiography and had similar coronary revascularization rates.

It is hypothesized that this lower rate of nonfatal myocardial infarction in patients with CTA plus standard care is associated with a higher rate of preventive therapies initiated in patients in the CTA-plus-standard-care group compared to standard care alone. However, the difference in the standard-care group should be noted when compared to the PROMISE trial. In the PROMISE trial, the comparator group had predominantly stress imaging (either nuclear stress test or echocardiography), while in the SCOT-HEART trial, the group had predominantly stress electrocardiogram (ECG), and only 10% of the patients underwent stress imaging. It is possible the difference seen in the rate of nonfatal myocardial infarction was due to suboptimal diagnosis of CAD with stress ECG, which has lower sensitivity compared to stress imaging.

The DISCHARGE trial investigated the effectiveness of CTA vs ICA as the initial diagnostic test in the management of patients with stable chest pain and an intermediate pretest probability of obstructive CAD.⁸ At 3.5 years of follow-up, the primary composite of cardiovascular death, myocardial infarction, or stroke was similar in both groups (2.1% vs 3.0; hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). Importantly, as fewer patients underwent ICA, the risk of procedure-related complication was lower in the CTA group than in the ICA group. However, it is important to note that only 25% of the patients diagnosed with obstructive CAD had greater than 50% vessel stenosis, which raises the question of whether an initial invasive strategy is appropriate for this population.

The strengths of these 2 studies include the large number of patients enrolled along with adequate follow-up, 5 years in the SCOT-HEART trial and 3.5 years in the DISCHARGE trial. The 2 studies overall suggest the usefulness of CTA for assessment of CAD. However, the control groups were very different in these 2 trials. In the SCOT-HEART study, the comparator group was primarily assessed by stress ECG, while in the DISCHARGE study, the comparator group was primary assessed by ICA. In the PROMISE trial, the composite end point of death, myocardial infarction, hospitalization for unstable angina, or major procedural complication was similar when the strategy of initial CTA was compared to functional testing with imaging (exercise ECG, nuclear stress testing, or echocardiography).⁵ Thus, clinical assessment is still needed when clinicians are selecting the appropriate diagnostic test for patients with suspected CAD. The most recent guidelines give similar recommendations for CTA compared to stress imaging.⁹ Whether further improvement in CTA acquisition or the addition of CT fractional flow reserve can further improve outcomes requires additional study.

Applications for Clinical Practice and System Implementation

In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful in diagnosis compared to stress ECG and in reducing utilization of low-yield ICA. Whether CTA is more useful compared to the other noninvasive stress imaging modalities in this population requires further study.

Practice Points

• In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful compared to stress ECG.
• Use of CTA can potentially reduce the use of low-yield coronary angiography.

–Thai Nguyen, MD, Albert Chan, MD, Taishi Hirai, MD
University of Missouri, Columbia, MO

Study 1 Overview (Bhasin et al)

Objective: To examine the effect of a multifactorial intervention for fall prevention on fall injury in community-dwelling older adults.

Design: This was a pragmatic, cluster randomized trial conducted in 86 primary care practices across 10 health care systems.

Setting and participants: The primary care sites were selected based on the prespecified criteria of size, ability to implement the intervention, proximity to other practices, accessibility to electronic health records, and access to community-based exercise programs. The primary care practices were randomly assigned to intervention or control.

Eligibility criteria for participants at those practices included age 70 years or older, dwelling in the community, and having an increased risk of falls, as determined by a history of fall-related injury in the past year, 2 or more falls in the past year, or being afraid of falling because of problems with balance or walking. Exclusion criteria were inability to provide consent or lack of proxy consent for participants who were determined to have cognitive impairment based on screening, and inability to speak English or Spanish. A total of 2802 participants were enrolled in the intervention group, and 2649 participants were enrolled in the control group.

Intervention: The intervention contained 5 components: a standardized assessment of 7 modifiable risk factors for fall injuries; standardized protocol-driven recommendations for management of risk factors; an individualized care plan focused on 1 to 3 risk factors; implementation of care plans, including referrals to community-based programs; and follow-up care conducted by telephone or in person. The modifiable risk factors included impairment of strength, gait, or balance; use of medications related to falls; postural hypotension; problems with feet or footwear; visual impairment; osteoporosis or vitamin D deficiency; and home safety hazards. The intervention was delivered by nurses who had completed online training modules and face-to-face training sessions focused on the intervention and motivational interviewing along with continuing education, in partnership with participants and their primary care providers. In the control group, participants received enhanced usual care, including an informational pamphlet, and were encouraged to discuss fall prevention with their primary care provider, including the results of their screening evaluation.

Main outcome measures: The primary outcome of the study was the first serious fall injury in a time-to-event analysis, defined as a fall resulting in a fracture (other than thoracic or lumbar vertebral fracture), joint dislocation, cut requiring closure, head injury requiring hospitalization, sprain or strain, bruising or swelling, or other serious injury. The secondary outcome was first patient-reported fall injury, also in a time-to-event analysis, ascertained by telephone interviews conducted every 4 months. Other outcomes included hospital admissions, emergency department visits, and other health care utilization. Adjudication of fall events and injuries was conducted by a team blinded to treatment assignment and verified using administrative claims data, encounter data, or electronic health record review.

Main results: The intervention and control groups were similar in terms of sex and age: 62.5% vs 61.5% of participants were women, and mean (SD) age was 79.9 (5.7) years and 79.5 (5.8) years, respectively. Other demographic characteristics were similar between groups. For the primary outcome, the rate of first serious injury was 4.9 per 100 person-years in the intervention group and 5.3 per 100 person-years in the control group, with a hazard ratio of 0.92 (95% CI, 0.80-1.06; P = .25). For the secondary outcome of patient-reported fall injury, there were 25.6 events per 100 person-years in the intervention group and 28.6 in the control group, with a hazard ratio of 0.90 (95% CI, 0.83-0.99; P =0.004). Rates of hospitalization and other secondary outcomes were similar between groups.

Conclusion: The multifactorial STRIDE intervention did not reduce the rate of serious fall injury when compared to enhanced usual care. The intervention did result in lower rates of fall injury by patient report, but no other significant outcomes were seen.

Study 2 Overview (Stark et al)

Objective: To examine the effect of a behavioral home hazard removal intervention for fall prevention on risk of fall in community-dwelling older adults.

Design: This randomized clinical trial was conducted at a single site in St. Louis, Missouri. Participants were community-dwelling older adults who received services from the Area Agency on Aging (AAA). Inclusion criteria included age 65 years and older, having 1 or more falls in the previous 12 months or being worried about falling by self report, and currently receiving services from an AAA. Exclusion criteria included living in an institution or being severely cognitively impaired and unable to follow directions or report falls. Participants who met the criteria were contacted by phone and invited to participate. A total of 310 participants were enrolled in the study, with an equal number of participants assigned to the intervention and control groups.

Intervention: The intervention included hazard identification and removal after a comprehensive assessment of participants, their behaviors, and the environment; this assessment took place during the first visit, which lasted approximately 80 minutes. A home hazard removal plan was developed, and in the second session, which lasted approximately 40 minutes, remediation of hazards was carried out. A third session for home modification that lasted approximately 30 minutes was conducted, if needed. At 6 months after the intervention, a booster session to identify and remediate any new home hazards and address issues was conducted. Specific interventions, as identified by the assessment, included minor home repair such as grab bars, adaptive equipment, task modification, and education. Shared decision making that enabled older adults to control changes in their homes, self-management strategies to improve awareness, and motivational enhancement strategies to improve acceptance were employed. Scripted algorithms and checklists were used to deliver the intervention. For usual care, an annual assessment and referrals to community services, if needed, were conducted in the AAA.

Main outcome measures: The primary outcome of the study was the number of days to first fall in 12 months. Falls were defined as unintentional movements to the floor, ground, or object below knee level, and falls were recorded through a daily journal for 12 months. Participants were contacted by phone if they did not return the journal or reported a fall. Participants were interviewed to verify falls and determine whether a fall was injurious. Secondary outcomes included rate of falls per person per 12 months; daily activity performance measured using the Older Americans Resources and Services Activities of Daily Living scale; falls self-efficacy, which measures confidence performing daily activities without falling; and quality of life using the SF-36 at 12 months.

Main results: Most of the study participants were women (74%), and mean (SD) age was 75 (7.4) years. Study retention was similar between the intervention and control groups, with 82% completing the study in the intervention group compared with 81% in the control group. Fidelity to the intervention, as measured by a checklist by the interventionist, was 99%, and adherence to home modification, as measured by number of home modifications in use by self report, was high at 92% at 6 months and 91% at 12 months. For the primary outcome, fall hazard was not different between the intervention and control groups (hazard ratio, 0.9; 95% CI, 0.66-1.27). For the secondary outcomes, the rate of falling was lower in the intervention group compared with the control group, with a relative risk of 0.62 (95% CI, 0.40-0.95). There was no difference in other secondary outcomes of daily activity performance, falls self-efficacy, or quality of life.

Conclusion: Despite high adherence to home modifications and fidelity to the intervention, this home hazard removal program did not reduce the risk of falling when compared to usual care. It did reduce the rate of falls, although no other effects were observed.

Commentary

Observational studies have identified factors that contribute to falls,¹ and over the past 30 years a number of intervention trials designed to reduce the risk of falling have been conducted. A recent Cochrane review, published prior to the Bhasin et al and Stark et al trials, looked at the effect of multifactorial interventions for fall prevention across 62 trials that included 19,935 older adults living in the community. The review concluded that multifactorial interventions may reduce the rate of falls, but this conclusion was based on low-quality evidence and there was significant heterogeneity across the studies.²

The STRIDE randomized trial represents the latest effort to address the evidence gap around fall prevention, with the STRIDE investigators hoping this would be the definitive trial that leads to practice change in fall prevention. Smaller trials that have demonstrated effectiveness were brought to scale in this large randomized trial that included 86 practices and more than 5000 participants. The investigators used risk of injurious falls as the primary outcome, as this outcome is considered the most clinically meaningful for the study population. The results, however, were disappointing: the multifactorial intervention in STRIDE did not result in a reduction of risk of injurious falls. Challenges in the implementation of this large trial may have contributed to its results; falls care managers, key to this multifactorial intervention, reported difficulties in navigating complex relationships with patients, families, study staff, and primary care practices during the study. Barriers reported included clinical space limitations, variable buy-in from providers, and turnover of practice staff and providers.³ Such implementation factors may have resulted in the divergent results between smaller clinical trials and this large-scale trial conducted across multiple settings.

The second study, by Stark et al, examined a home modification program and its effect on risk of falls. A prior Cochrane review examining the effect of home safety assessment and modification indicates that these strategies are effective in reducing the rate of falls as well as the risk of falling.⁴ The results of the current trial showed a reduction in the rate of falls but not in the risk of falling; however, this study did not examine outcomes of serious injurious falls, which may be more clinically meaningful. The Stark et al study adds to the existing literature showing that home modification may have an impact on fall rates. One noteworthy aspect of the Stark et al trial is the high adherence rate to home modification in a community-based approach; perhaps the investigators’ approach can be translated to real-world use.

Applications for Clinical Practice and System Implementation

The role of exercise programs in reducing fall rates is well established,⁵ but neither of these studies focused on exercise interventions. STRIDE offered community-based exercise program referral, but there is variability in such programs and study staff reported challenges in matching participants with appropriate exercise programs.³ Further studies that examine combinations of multifactorial falls risk reduction, exercise, and home safety, with careful consideration of implementation challenges to assure fidelity and adherence to the intervention, are needed to ascertain the best strategy for fall prevention for older adults at risk.

Given the results of these trials, it is difficult to recommend one falls prevention intervention over another. Clinicians should continue to identify falls risk factors using standardized assessments and determine which factors are modifiable.

Practice Points

• Incorporating assessments of falls risk in primary care is feasible, and such assessments can identify important risk factors.
• Clinicians and health systems should identify avenues, such as developing programmatic approaches, to providing home safety assessment and intervention, exercise options, medication review, and modification of other risk factors.
• Ensuring delivery of these elements reliably through programmatic approaches with adequate follow-up is key to preventing falls in this population.

—William W. Hung, MD, MPH

Study 1 Overview (Bhasin et al)

Objective: To examine the effect of a multifactorial intervention for fall prevention on fall injury in community-dwelling older adults.

Design: This was a pragmatic, cluster randomized trial conducted in 86 primary care practices across 10 health care systems.

Setting and participants: The primary care sites were selected based on the prespecified criteria of size, ability to implement the intervention, proximity to other practices, accessibility to electronic health records, and access to community-based exercise programs. The primary care practices were randomly assigned to intervention or control.

Eligibility criteria for participants at those practices included age 70 years or older, dwelling in the community, and having an increased risk of falls, as determined by a history of fall-related injury in the past year, 2 or more falls in the past year, or being afraid of falling because of problems with balance or walking. Exclusion criteria were inability to provide consent or lack of proxy consent for participants who were determined to have cognitive impairment based on screening, and inability to speak English or Spanish. A total of 2802 participants were enrolled in the intervention group, and 2649 participants were enrolled in the control group.

Intervention: The intervention contained 5 components: a standardized assessment of 7 modifiable risk factors for fall injuries; standardized protocol-driven recommendations for management of risk factors; an individualized care plan focused on 1 to 3 risk factors; implementation of care plans, including referrals to community-based programs; and follow-up care conducted by telephone or in person. The modifiable risk factors included impairment of strength, gait, or balance; use of medications related to falls; postural hypotension; problems with feet or footwear; visual impairment; osteoporosis or vitamin D deficiency; and home safety hazards. The intervention was delivered by nurses who had completed online training modules and face-to-face training sessions focused on the intervention and motivational interviewing along with continuing education, in partnership with participants and their primary care providers. In the control group, participants received enhanced usual care, including an informational pamphlet, and were encouraged to discuss fall prevention with their primary care provider, including the results of their screening evaluation.

Main outcome measures: The primary outcome of the study was the first serious fall injury in a time-to-event analysis, defined as a fall resulting in a fracture (other than thoracic or lumbar vertebral fracture), joint dislocation, cut requiring closure, head injury requiring hospitalization, sprain or strain, bruising or swelling, or other serious injury. The secondary outcome was first patient-reported fall injury, also in a time-to-event analysis, ascertained by telephone interviews conducted every 4 months. Other outcomes included hospital admissions, emergency department visits, and other health care utilization. Adjudication of fall events and injuries was conducted by a team blinded to treatment assignment and verified using administrative claims data, encounter data, or electronic health record review.

Main results: The intervention and control groups were similar in terms of sex and age: 62.5% vs 61.5% of participants were women, and mean (SD) age was 79.9 (5.7) years and 79.5 (5.8) years, respectively. Other demographic characteristics were similar between groups. For the primary outcome, the rate of first serious injury was 4.9 per 100 person-years in the intervention group and 5.3 per 100 person-years in the control group, with a hazard ratio of 0.92 (95% CI, 0.80-1.06; P = .25). For the secondary outcome of patient-reported fall injury, there were 25.6 events per 100 person-years in the intervention group and 28.6 in the control group, with a hazard ratio of 0.90 (95% CI, 0.83-0.99; P =0.004). Rates of hospitalization and other secondary outcomes were similar between groups.

Conclusion: The multifactorial STRIDE intervention did not reduce the rate of serious fall injury when compared to enhanced usual care. The intervention did result in lower rates of fall injury by patient report, but no other significant outcomes were seen.

Study 2 Overview (Stark et al)

Objective: To examine the effect of a behavioral home hazard removal intervention for fall prevention on risk of fall in community-dwelling older adults.

Design: This randomized clinical trial was conducted at a single site in St. Louis, Missouri. Participants were community-dwelling older adults who received services from the Area Agency on Aging (AAA). Inclusion criteria included age 65 years and older, having 1 or more falls in the previous 12 months or being worried about falling by self report, and currently receiving services from an AAA. Exclusion criteria included living in an institution or being severely cognitively impaired and unable to follow directions or report falls. Participants who met the criteria were contacted by phone and invited to participate. A total of 310 participants were enrolled in the study, with an equal number of participants assigned to the intervention and control groups.

Intervention: The intervention included hazard identification and removal after a comprehensive assessment of participants, their behaviors, and the environment; this assessment took place during the first visit, which lasted approximately 80 minutes. A home hazard removal plan was developed, and in the second session, which lasted approximately 40 minutes, remediation of hazards was carried out. A third session for home modification that lasted approximately 30 minutes was conducted, if needed. At 6 months after the intervention, a booster session to identify and remediate any new home hazards and address issues was conducted. Specific interventions, as identified by the assessment, included minor home repair such as grab bars, adaptive equipment, task modification, and education. Shared decision making that enabled older adults to control changes in their homes, self-management strategies to improve awareness, and motivational enhancement strategies to improve acceptance were employed. Scripted algorithms and checklists were used to deliver the intervention. For usual care, an annual assessment and referrals to community services, if needed, were conducted in the AAA.

Main outcome measures: The primary outcome of the study was the number of days to first fall in 12 months. Falls were defined as unintentional movements to the floor, ground, or object below knee level, and falls were recorded through a daily journal for 12 months. Participants were contacted by phone if they did not return the journal or reported a fall. Participants were interviewed to verify falls and determine whether a fall was injurious. Secondary outcomes included rate of falls per person per 12 months; daily activity performance measured using the Older Americans Resources and Services Activities of Daily Living scale; falls self-efficacy, which measures confidence performing daily activities without falling; and quality of life using the SF-36 at 12 months.

Main results: Most of the study participants were women (74%), and mean (SD) age was 75 (7.4) years. Study retention was similar between the intervention and control groups, with 82% completing the study in the intervention group compared with 81% in the control group. Fidelity to the intervention, as measured by a checklist by the interventionist, was 99%, and adherence to home modification, as measured by number of home modifications in use by self report, was high at 92% at 6 months and 91% at 12 months. For the primary outcome, fall hazard was not different between the intervention and control groups (hazard ratio, 0.9; 95% CI, 0.66-1.27). For the secondary outcomes, the rate of falling was lower in the intervention group compared with the control group, with a relative risk of 0.62 (95% CI, 0.40-0.95). There was no difference in other secondary outcomes of daily activity performance, falls self-efficacy, or quality of life.

Conclusion: Despite high adherence to home modifications and fidelity to the intervention, this home hazard removal program did not reduce the risk of falling when compared to usual care. It did reduce the rate of falls, although no other effects were observed.

Commentary

Observational studies have identified factors that contribute to falls,¹ and over the past 30 years a number of intervention trials designed to reduce the risk of falling have been conducted. A recent Cochrane review, published prior to the Bhasin et al and Stark et al trials, looked at the effect of multifactorial interventions for fall prevention across 62 trials that included 19,935 older adults living in the community. The review concluded that multifactorial interventions may reduce the rate of falls, but this conclusion was based on low-quality evidence and there was significant heterogeneity across the studies.²

The STRIDE randomized trial represents the latest effort to address the evidence gap around fall prevention, with the STRIDE investigators hoping this would be the definitive trial that leads to practice change in fall prevention. Smaller trials that have demonstrated effectiveness were brought to scale in this large randomized trial that included 86 practices and more than 5000 participants. The investigators used risk of injurious falls as the primary outcome, as this outcome is considered the most clinically meaningful for the study population. The results, however, were disappointing: the multifactorial intervention in STRIDE did not result in a reduction of risk of injurious falls. Challenges in the implementation of this large trial may have contributed to its results; falls care managers, key to this multifactorial intervention, reported difficulties in navigating complex relationships with patients, families, study staff, and primary care practices during the study. Barriers reported included clinical space limitations, variable buy-in from providers, and turnover of practice staff and providers.³ Such implementation factors may have resulted in the divergent results between smaller clinical trials and this large-scale trial conducted across multiple settings.

The second study, by Stark et al, examined a home modification program and its effect on risk of falls. A prior Cochrane review examining the effect of home safety assessment and modification indicates that these strategies are effective in reducing the rate of falls as well as the risk of falling.⁴ The results of the current trial showed a reduction in the rate of falls but not in the risk of falling; however, this study did not examine outcomes of serious injurious falls, which may be more clinically meaningful. The Stark et al study adds to the existing literature showing that home modification may have an impact on fall rates. One noteworthy aspect of the Stark et al trial is the high adherence rate to home modification in a community-based approach; perhaps the investigators’ approach can be translated to real-world use.

Applications for Clinical Practice and System Implementation

The role of exercise programs in reducing fall rates is well established,⁵ but neither of these studies focused on exercise interventions. STRIDE offered community-based exercise program referral, but there is variability in such programs and study staff reported challenges in matching participants with appropriate exercise programs.³ Further studies that examine combinations of multifactorial falls risk reduction, exercise, and home safety, with careful consideration of implementation challenges to assure fidelity and adherence to the intervention, are needed to ascertain the best strategy for fall prevention for older adults at risk.

Given the results of these trials, it is difficult to recommend one falls prevention intervention over another. Clinicians should continue to identify falls risk factors using standardized assessments and determine which factors are modifiable.

Practice Points

• Incorporating assessments of falls risk in primary care is feasible, and such assessments can identify important risk factors.
• Clinicians and health systems should identify avenues, such as developing programmatic approaches, to providing home safety assessment and intervention, exercise options, medication review, and modification of other risk factors.
• Ensuring delivery of these elements reliably through programmatic approaches with adequate follow-up is key to preventing falls in this population.

—William W. Hung, MD, MPH

Study 1 Overview (Bhasin et al)

Objective: To examine the effect of a multifactorial intervention for fall prevention on fall injury in community-dwelling older adults.

Design: This was a pragmatic, cluster randomized trial conducted in 86 primary care practices across 10 health care systems.

Setting and participants: The primary care sites were selected based on the prespecified criteria of size, ability to implement the intervention, proximity to other practices, accessibility to electronic health records, and access to community-based exercise programs. The primary care practices were randomly assigned to intervention or control.

Eligibility criteria for participants at those practices included age 70 years or older, dwelling in the community, and having an increased risk of falls, as determined by a history of fall-related injury in the past year, 2 or more falls in the past year, or being afraid of falling because of problems with balance or walking. Exclusion criteria were inability to provide consent or lack of proxy consent for participants who were determined to have cognitive impairment based on screening, and inability to speak English or Spanish. A total of 2802 participants were enrolled in the intervention group, and 2649 participants were enrolled in the control group.

Intervention: The intervention contained 5 components: a standardized assessment of 7 modifiable risk factors for fall injuries; standardized protocol-driven recommendations for management of risk factors; an individualized care plan focused on 1 to 3 risk factors; implementation of care plans, including referrals to community-based programs; and follow-up care conducted by telephone or in person. The modifiable risk factors included impairment of strength, gait, or balance; use of medications related to falls; postural hypotension; problems with feet or footwear; visual impairment; osteoporosis or vitamin D deficiency; and home safety hazards. The intervention was delivered by nurses who had completed online training modules and face-to-face training sessions focused on the intervention and motivational interviewing along with continuing education, in partnership with participants and their primary care providers. In the control group, participants received enhanced usual care, including an informational pamphlet, and were encouraged to discuss fall prevention with their primary care provider, including the results of their screening evaluation.

Main outcome measures: The primary outcome of the study was the first serious fall injury in a time-to-event analysis, defined as a fall resulting in a fracture (other than thoracic or lumbar vertebral fracture), joint dislocation, cut requiring closure, head injury requiring hospitalization, sprain or strain, bruising or swelling, or other serious injury. The secondary outcome was first patient-reported fall injury, also in a time-to-event analysis, ascertained by telephone interviews conducted every 4 months. Other outcomes included hospital admissions, emergency department visits, and other health care utilization. Adjudication of fall events and injuries was conducted by a team blinded to treatment assignment and verified using administrative claims data, encounter data, or electronic health record review.

Main results: The intervention and control groups were similar in terms of sex and age: 62.5% vs 61.5% of participants were women, and mean (SD) age was 79.9 (5.7) years and 79.5 (5.8) years, respectively. Other demographic characteristics were similar between groups. For the primary outcome, the rate of first serious injury was 4.9 per 100 person-years in the intervention group and 5.3 per 100 person-years in the control group, with a hazard ratio of 0.92 (95% CI, 0.80-1.06; P = .25). For the secondary outcome of patient-reported fall injury, there were 25.6 events per 100 person-years in the intervention group and 28.6 in the control group, with a hazard ratio of 0.90 (95% CI, 0.83-0.99; P =0.004). Rates of hospitalization and other secondary outcomes were similar between groups.

Conclusion: The multifactorial STRIDE intervention did not reduce the rate of serious fall injury when compared to enhanced usual care. The intervention did result in lower rates of fall injury by patient report, but no other significant outcomes were seen.

Study 2 Overview (Stark et al)

Objective: To examine the effect of a behavioral home hazard removal intervention for fall prevention on risk of fall in community-dwelling older adults.

Design: This randomized clinical trial was conducted at a single site in St. Louis, Missouri. Participants were community-dwelling older adults who received services from the Area Agency on Aging (AAA). Inclusion criteria included age 65 years and older, having 1 or more falls in the previous 12 months or being worried about falling by self report, and currently receiving services from an AAA. Exclusion criteria included living in an institution or being severely cognitively impaired and unable to follow directions or report falls. Participants who met the criteria were contacted by phone and invited to participate. A total of 310 participants were enrolled in the study, with an equal number of participants assigned to the intervention and control groups.

Intervention: The intervention included hazard identification and removal after a comprehensive assessment of participants, their behaviors, and the environment; this assessment took place during the first visit, which lasted approximately 80 minutes. A home hazard removal plan was developed, and in the second session, which lasted approximately 40 minutes, remediation of hazards was carried out. A third session for home modification that lasted approximately 30 minutes was conducted, if needed. At 6 months after the intervention, a booster session to identify and remediate any new home hazards and address issues was conducted. Specific interventions, as identified by the assessment, included minor home repair such as grab bars, adaptive equipment, task modification, and education. Shared decision making that enabled older adults to control changes in their homes, self-management strategies to improve awareness, and motivational enhancement strategies to improve acceptance were employed. Scripted algorithms and checklists were used to deliver the intervention. For usual care, an annual assessment and referrals to community services, if needed, were conducted in the AAA.

Main outcome measures: The primary outcome of the study was the number of days to first fall in 12 months. Falls were defined as unintentional movements to the floor, ground, or object below knee level, and falls were recorded through a daily journal for 12 months. Participants were contacted by phone if they did not return the journal or reported a fall. Participants were interviewed to verify falls and determine whether a fall was injurious. Secondary outcomes included rate of falls per person per 12 months; daily activity performance measured using the Older Americans Resources and Services Activities of Daily Living scale; falls self-efficacy, which measures confidence performing daily activities without falling; and quality of life using the SF-36 at 12 months.

Main results: Most of the study participants were women (74%), and mean (SD) age was 75 (7.4) years. Study retention was similar between the intervention and control groups, with 82% completing the study in the intervention group compared with 81% in the control group. Fidelity to the intervention, as measured by a checklist by the interventionist, was 99%, and adherence to home modification, as measured by number of home modifications in use by self report, was high at 92% at 6 months and 91% at 12 months. For the primary outcome, fall hazard was not different between the intervention and control groups (hazard ratio, 0.9; 95% CI, 0.66-1.27). For the secondary outcomes, the rate of falling was lower in the intervention group compared with the control group, with a relative risk of 0.62 (95% CI, 0.40-0.95). There was no difference in other secondary outcomes of daily activity performance, falls self-efficacy, or quality of life.

Conclusion: Despite high adherence to home modifications and fidelity to the intervention, this home hazard removal program did not reduce the risk of falling when compared to usual care. It did reduce the rate of falls, although no other effects were observed.

Commentary

Observational studies have identified factors that contribute to falls,¹ and over the past 30 years a number of intervention trials designed to reduce the risk of falling have been conducted. A recent Cochrane review, published prior to the Bhasin et al and Stark et al trials, looked at the effect of multifactorial interventions for fall prevention across 62 trials that included 19,935 older adults living in the community. The review concluded that multifactorial interventions may reduce the rate of falls, but this conclusion was based on low-quality evidence and there was significant heterogeneity across the studies.²

The STRIDE randomized trial represents the latest effort to address the evidence gap around fall prevention, with the STRIDE investigators hoping this would be the definitive trial that leads to practice change in fall prevention. Smaller trials that have demonstrated effectiveness were brought to scale in this large randomized trial that included 86 practices and more than 5000 participants. The investigators used risk of injurious falls as the primary outcome, as this outcome is considered the most clinically meaningful for the study population. The results, however, were disappointing: the multifactorial intervention in STRIDE did not result in a reduction of risk of injurious falls. Challenges in the implementation of this large trial may have contributed to its results; falls care managers, key to this multifactorial intervention, reported difficulties in navigating complex relationships with patients, families, study staff, and primary care practices during the study. Barriers reported included clinical space limitations, variable buy-in from providers, and turnover of practice staff and providers.³ Such implementation factors may have resulted in the divergent results between smaller clinical trials and this large-scale trial conducted across multiple settings.

The second study, by Stark et al, examined a home modification program and its effect on risk of falls. A prior Cochrane review examining the effect of home safety assessment and modification indicates that these strategies are effective in reducing the rate of falls as well as the risk of falling.⁴ The results of the current trial showed a reduction in the rate of falls but not in the risk of falling; however, this study did not examine outcomes of serious injurious falls, which may be more clinically meaningful. The Stark et al study adds to the existing literature showing that home modification may have an impact on fall rates. One noteworthy aspect of the Stark et al trial is the high adherence rate to home modification in a community-based approach; perhaps the investigators’ approach can be translated to real-world use.

Applications for Clinical Practice and System Implementation

The role of exercise programs in reducing fall rates is well established,⁵ but neither of these studies focused on exercise interventions. STRIDE offered community-based exercise program referral, but there is variability in such programs and study staff reported challenges in matching participants with appropriate exercise programs.³ Further studies that examine combinations of multifactorial falls risk reduction, exercise, and home safety, with careful consideration of implementation challenges to assure fidelity and adherence to the intervention, are needed to ascertain the best strategy for fall prevention for older adults at risk.

Given the results of these trials, it is difficult to recommend one falls prevention intervention over another. Clinicians should continue to identify falls risk factors using standardized assessments and determine which factors are modifiable.

Practice Points

• Incorporating assessments of falls risk in primary care is feasible, and such assessments can identify important risk factors.
• Clinicians and health systems should identify avenues, such as developing programmatic approaches, to providing home safety assessment and intervention, exercise options, medication review, and modification of other risk factors.
• Ensuring delivery of these elements reliably through programmatic approaches with adequate follow-up is key to preventing falls in this population.

—William W. Hung, MD, MPH

SAN DIEGO – Patients with acute cholangitis are twice as likely to be readmitted within 30 days if they don’t get a cholecystectomy in the same hospital admission for which they get biliary decompression, researchers say.

The readmissions result mostly from sepsis and recurrence of the acute cholangitis, said Ahmad Khan, MD, MS, a gastroenterology fellow at Case Western Reserve University in Cleveland, at Digestive Diseases Week^® (DDW) 2022. “These added readmissions can cause a significant burden in terms of costs and extra days of hospitalization in these patients.”

Acute cholangitis in patients without bile duct stents is most often caused by biliary calculi, benign biliary stricture, or malignancy. A gastrointestinal emergency, it requires treatment with biliary decompression followed by cholecystectomy, but the cholecystectomy is considered an elective procedure.

Surgeons may delay it if the patient is very sick, or simply for scheduling reasons, Dr. Khan said. “There are some areas where the surgeons may be too busy,” he said. Or if the patient first presents at the end of the week, some surgeons will send the patient home so they don’t have to operate on the weekend, he said.

To understand the consequences of these decisions, Dr. Khan and his colleagues analyzed data from 2016 to 2018 from the National Readmission Database of the U.S. Agency for Healthcare Research and Quality.

They found that 11% of patients who went home before returning for a cholecystectomy had to be readmitted versus only 5.5% of those who got a cholecystectomy during the same (index) admission as their biliary decompression.

Patients who got cholecystectomies during their index admissions were slightly younger and healthier: Their mean age was 67.29 years and 20.59% had three or more comorbidities at index admission versus 70.77 years of age and 39.80% with three or more comorbidities at index admission for those who got their cholecystectomies later.

The researchers did not find any significant differences in the hospitals’ characteristics, such as being urban or academic, between the two groups.

Mortality was higher for those who received their cholecystectomy after returning home, but they spent less time in the hospital at lower total cost. The differences in outcomes between the index admission and readmission were all statistically significant (P < .01).

This observational study could not determine cause and effect, but it justifies a prospective trial that could more definitely determine which approach results in better outcomes, Dr. Khan said.

That patients are less likely to need readmission if they return home without a gall bladder after treatment for acute cholangitis “makes sense,” said session comoderator Richard Sterling, MD, MSc, chief of hepatology at Virginia Commonwealth University in Richmond.

“Should you do it immediately or can you wait a day or 2? They didn’t really address when during that admission, so we still don’t know the optimal sequence of events.”

If a patient has so many comorbidities that the surgeon and anesthesiologist don’t think the patient could survive a cholecystectomy, then the surgeon might do a cholecystostomy instead, he said.

Dr. Khan said he hopes to delve deeper into the data to determine what factors might have influenced the surgeons’ decisions to delay the cholecystectomy. “I want to see, of the patients who did not get same-admission cholecystectomies, how many had diabetes, how many had coronary artery disease, how many were on blood thinners, and things like that.”

Neither Dr. Khan nor Dr. Sterling reported any relevant financial interests.

SAN DIEGO – Patients with acute cholangitis are twice as likely to be readmitted within 30 days if they don’t get a cholecystectomy in the same hospital admission for which they get biliary decompression, researchers say.

The readmissions result mostly from sepsis and recurrence of the acute cholangitis, said Ahmad Khan, MD, MS, a gastroenterology fellow at Case Western Reserve University in Cleveland, at Digestive Diseases Week^® (DDW) 2022. “These added readmissions can cause a significant burden in terms of costs and extra days of hospitalization in these patients.”

Acute cholangitis in patients without bile duct stents is most often caused by biliary calculi, benign biliary stricture, or malignancy. A gastrointestinal emergency, it requires treatment with biliary decompression followed by cholecystectomy, but the cholecystectomy is considered an elective procedure.

Surgeons may delay it if the patient is very sick, or simply for scheduling reasons, Dr. Khan said. “There are some areas where the surgeons may be too busy,” he said. Or if the patient first presents at the end of the week, some surgeons will send the patient home so they don’t have to operate on the weekend, he said.

To understand the consequences of these decisions, Dr. Khan and his colleagues analyzed data from 2016 to 2018 from the National Readmission Database of the U.S. Agency for Healthcare Research and Quality.

They found that 11% of patients who went home before returning for a cholecystectomy had to be readmitted versus only 5.5% of those who got a cholecystectomy during the same (index) admission as their biliary decompression.

Patients who got cholecystectomies during their index admissions were slightly younger and healthier: Their mean age was 67.29 years and 20.59% had three or more comorbidities at index admission versus 70.77 years of age and 39.80% with three or more comorbidities at index admission for those who got their cholecystectomies later.

The researchers did not find any significant differences in the hospitals’ characteristics, such as being urban or academic, between the two groups.

Mortality was higher for those who received their cholecystectomy after returning home, but they spent less time in the hospital at lower total cost. The differences in outcomes between the index admission and readmission were all statistically significant (P < .01).

This observational study could not determine cause and effect, but it justifies a prospective trial that could more definitely determine which approach results in better outcomes, Dr. Khan said.

That patients are less likely to need readmission if they return home without a gall bladder after treatment for acute cholangitis “makes sense,” said session comoderator Richard Sterling, MD, MSc, chief of hepatology at Virginia Commonwealth University in Richmond.

“Should you do it immediately or can you wait a day or 2? They didn’t really address when during that admission, so we still don’t know the optimal sequence of events.”

If a patient has so many comorbidities that the surgeon and anesthesiologist don’t think the patient could survive a cholecystectomy, then the surgeon might do a cholecystostomy instead, he said.

Dr. Khan said he hopes to delve deeper into the data to determine what factors might have influenced the surgeons’ decisions to delay the cholecystectomy. “I want to see, of the patients who did not get same-admission cholecystectomies, how many had diabetes, how many had coronary artery disease, how many were on blood thinners, and things like that.”

Neither Dr. Khan nor Dr. Sterling reported any relevant financial interests.

SAN DIEGO – Patients with acute cholangitis are twice as likely to be readmitted within 30 days if they don’t get a cholecystectomy in the same hospital admission for which they get biliary decompression, researchers say.

The readmissions result mostly from sepsis and recurrence of the acute cholangitis, said Ahmad Khan, MD, MS, a gastroenterology fellow at Case Western Reserve University in Cleveland, at Digestive Diseases Week^® (DDW) 2022. “These added readmissions can cause a significant burden in terms of costs and extra days of hospitalization in these patients.”

Acute cholangitis in patients without bile duct stents is most often caused by biliary calculi, benign biliary stricture, or malignancy. A gastrointestinal emergency, it requires treatment with biliary decompression followed by cholecystectomy, but the cholecystectomy is considered an elective procedure.

Surgeons may delay it if the patient is very sick, or simply for scheduling reasons, Dr. Khan said. “There are some areas where the surgeons may be too busy,” he said. Or if the patient first presents at the end of the week, some surgeons will send the patient home so they don’t have to operate on the weekend, he said.

To understand the consequences of these decisions, Dr. Khan and his colleagues analyzed data from 2016 to 2018 from the National Readmission Database of the U.S. Agency for Healthcare Research and Quality.

They found that 11% of patients who went home before returning for a cholecystectomy had to be readmitted versus only 5.5% of those who got a cholecystectomy during the same (index) admission as their biliary decompression.

Patients who got cholecystectomies during their index admissions were slightly younger and healthier: Their mean age was 67.29 years and 20.59% had three or more comorbidities at index admission versus 70.77 years of age and 39.80% with three or more comorbidities at index admission for those who got their cholecystectomies later.

The researchers did not find any significant differences in the hospitals’ characteristics, such as being urban or academic, between the two groups.

Mortality was higher for those who received their cholecystectomy after returning home, but they spent less time in the hospital at lower total cost. The differences in outcomes between the index admission and readmission were all statistically significant (P < .01).

This observational study could not determine cause and effect, but it justifies a prospective trial that could more definitely determine which approach results in better outcomes, Dr. Khan said.

That patients are less likely to need readmission if they return home without a gall bladder after treatment for acute cholangitis “makes sense,” said session comoderator Richard Sterling, MD, MSc, chief of hepatology at Virginia Commonwealth University in Richmond.

“Should you do it immediately or can you wait a day or 2? They didn’t really address when during that admission, so we still don’t know the optimal sequence of events.”

If a patient has so many comorbidities that the surgeon and anesthesiologist don’t think the patient could survive a cholecystectomy, then the surgeon might do a cholecystostomy instead, he said.

Dr. Khan said he hopes to delve deeper into the data to determine what factors might have influenced the surgeons’ decisions to delay the cholecystectomy. “I want to see, of the patients who did not get same-admission cholecystectomies, how many had diabetes, how many had coronary artery disease, how many were on blood thinners, and things like that.”

Neither Dr. Khan nor Dr. Sterling reported any relevant financial interests.

Sparring among professional mixed martial arts (MMA) practitioners may have both positive and negative effects on the brain, early research suggests.

Investigators found sparring, defined as strategically hitting opponents with kicks, punches, and other strikes during practice sessions, is linked to increased white matter hyperintensities in the brain, pointing to possible vascular damage from repeated head trauma. However, the study results also show sparring was associated with a larger bilateral caudate which, in theory, is neuroprotective.

“From our preliminary study, sparring practice in MMA fighters may have a ‘double-edged sword’ effect on the brain,” study investigator Aaron Esagoff, a second-year medical student at Johns Hopkins University School of Medicine, Baltimore, told this news organization.

Growing popularity

MMA is a full-contact combat sport that has become increasingly popular over the past 15 years. It combines techniques from boxing, wrestling, karate, judo, and jujitsu.

To prepare for fights, MMA practitioners incorporate sparring and grappling, which use techniques such as chokes and locks to submit an opponent. Head protection is sometimes incorporated during practice, but is not the norm during a fight, said Mr. Esagoff.

The study investigated sparring during practice rather than fights because, he said, MMA competitors only fight a few times a year but spend hundreds of hours training. “So the health effects of training are going to be really important,” he said.

As with other combat sports, MMA involves hits to the head. Previous research has shown repetitive head trauma can lead to neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Alzheimer’s disease, Mr. Esagoff noted.

Previous studies have also linked more professional fights and years of fighting to a decrease in brain volume among MMA fighters, he added.

The new analysis was conducted as part of the Professional Fighters Brain Health Study, a longitudinal cohort study of MMA professional fighters. It included 92 fighters with data available on MRI and habits regarding practicing. The mean age of the participants was 30 years, 62% were White, and 85% were men.

The study examined sparring but did not include grappling because of “several challenges” with the current data analysis, Mr. Esagoff said. Researchers adjusted for age, sex, education, race, number of fights, total intracranial volume, and type of MRI scanner used.
 

A ‘highly strategic’ sport

Results showed a strong association between the number of sparring rounds per week and increased white matter hyperintensity volume (mcL) on MRI (P = .039).

This suggests white matter damage, possibly a result of direct neuronal injury, vascular damage, or immune modulation, said Mr. Esagoff. However, another mechanism may be involved, he added.

There was also a significant association between sparring and increased size of the caudate nucleus, an area of the brain involved in movement, learning, and memory (P = .014 for right caudate volume, P = .012 for left caudate volume).

There are some theories that might explain this finding, said Mr. Esagoff. For example, individuals who spar more may get better at avoiding impacts and injuries during a fight, which might in turn affect the size of the caudate.

The controlled movements and techniques used during sparring could also affect the caudate. “Some research has shown that behavior, learning, and/or exercise may increase the size of certain brain regions,” Mr. Esagoff said.

He noted the “highly strategic” nature of combat sports – and used the example of Brazilian jiu-jitsu. That sport “is known as human chess because it takes a thoughtful approach to defeat a larger opponent with base, leverage, and technique,” he said.

However, Mr. Esagoff stressed that while it is possible movements involved in MMA increase caudate size, this is just a theory at this point.

A study limitation was that fighters volunteered to participate and may not represent all fighters. As well, the study was cross-sectional and looked at only one point in time, so it cannot infer causation.

Overall, the new findings should help inform fighters, governing bodies, and the public about the potential risks and benefits of different styles of MMA fighting and practice, although more research is needed, said Mr. Esagoff.

He and his team now plan to conduct a longer-term study and investigate effects of grappling on brain structure and function in addition to sparring.
 

Jury still out

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry and incoming chair of the APA’s Council on Communications, said the jury “is clearly still out” when it comes to the investigation of brain impacts.

“We don’t know quite what these changes fully correlate to,” said Dr. Liu, who moderated a press briefing highlighting the study.

He underlined the importance of protecting athletes vulnerable to head trauma, be they professionals or those involved at the youth sports level.

Dr. Liu also noted the “extreme popularity” and rapid growth of MMA around the world, which he said provides an opportunity for researchers to study these professional fighters.

“This is a unique population that signed up in the midst of hundreds of hours of sparring to advance neuroscience, and that’s quite amazing,” he said.

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

Sparring among professional mixed martial arts (MMA) practitioners may have both positive and negative effects on the brain, early research suggests.

Investigators found sparring, defined as strategically hitting opponents with kicks, punches, and other strikes during practice sessions, is linked to increased white matter hyperintensities in the brain, pointing to possible vascular damage from repeated head trauma. However, the study results also show sparring was associated with a larger bilateral caudate which, in theory, is neuroprotective.

“From our preliminary study, sparring practice in MMA fighters may have a ‘double-edged sword’ effect on the brain,” study investigator Aaron Esagoff, a second-year medical student at Johns Hopkins University School of Medicine, Baltimore, told this news organization.

Growing popularity

MMA is a full-contact combat sport that has become increasingly popular over the past 15 years. It combines techniques from boxing, wrestling, karate, judo, and jujitsu.

To prepare for fights, MMA practitioners incorporate sparring and grappling, which use techniques such as chokes and locks to submit an opponent. Head protection is sometimes incorporated during practice, but is not the norm during a fight, said Mr. Esagoff.

The study investigated sparring during practice rather than fights because, he said, MMA competitors only fight a few times a year but spend hundreds of hours training. “So the health effects of training are going to be really important,” he said.

As with other combat sports, MMA involves hits to the head. Previous research has shown repetitive head trauma can lead to neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Alzheimer’s disease, Mr. Esagoff noted.

Previous studies have also linked more professional fights and years of fighting to a decrease in brain volume among MMA fighters, he added.

The new analysis was conducted as part of the Professional Fighters Brain Health Study, a longitudinal cohort study of MMA professional fighters. It included 92 fighters with data available on MRI and habits regarding practicing. The mean age of the participants was 30 years, 62% were White, and 85% were men.

The study examined sparring but did not include grappling because of “several challenges” with the current data analysis, Mr. Esagoff said. Researchers adjusted for age, sex, education, race, number of fights, total intracranial volume, and type of MRI scanner used.
 

A ‘highly strategic’ sport

Results showed a strong association between the number of sparring rounds per week and increased white matter hyperintensity volume (mcL) on MRI (P = .039).

This suggests white matter damage, possibly a result of direct neuronal injury, vascular damage, or immune modulation, said Mr. Esagoff. However, another mechanism may be involved, he added.

There was also a significant association between sparring and increased size of the caudate nucleus, an area of the brain involved in movement, learning, and memory (P = .014 for right caudate volume, P = .012 for left caudate volume).

There are some theories that might explain this finding, said Mr. Esagoff. For example, individuals who spar more may get better at avoiding impacts and injuries during a fight, which might in turn affect the size of the caudate.

The controlled movements and techniques used during sparring could also affect the caudate. “Some research has shown that behavior, learning, and/or exercise may increase the size of certain brain regions,” Mr. Esagoff said.

He noted the “highly strategic” nature of combat sports – and used the example of Brazilian jiu-jitsu. That sport “is known as human chess because it takes a thoughtful approach to defeat a larger opponent with base, leverage, and technique,” he said.

However, Mr. Esagoff stressed that while it is possible movements involved in MMA increase caudate size, this is just a theory at this point.

A study limitation was that fighters volunteered to participate and may not represent all fighters. As well, the study was cross-sectional and looked at only one point in time, so it cannot infer causation.

Overall, the new findings should help inform fighters, governing bodies, and the public about the potential risks and benefits of different styles of MMA fighting and practice, although more research is needed, said Mr. Esagoff.

He and his team now plan to conduct a longer-term study and investigate effects of grappling on brain structure and function in addition to sparring.
 

Jury still out

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry and incoming chair of the APA’s Council on Communications, said the jury “is clearly still out” when it comes to the investigation of brain impacts.

“We don’t know quite what these changes fully correlate to,” said Dr. Liu, who moderated a press briefing highlighting the study.

He underlined the importance of protecting athletes vulnerable to head trauma, be they professionals or those involved at the youth sports level.

Dr. Liu also noted the “extreme popularity” and rapid growth of MMA around the world, which he said provides an opportunity for researchers to study these professional fighters.

“This is a unique population that signed up in the midst of hundreds of hours of sparring to advance neuroscience, and that’s quite amazing,” he said.

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

Sparring among professional mixed martial arts (MMA) practitioners may have both positive and negative effects on the brain, early research suggests.

Investigators found sparring, defined as strategically hitting opponents with kicks, punches, and other strikes during practice sessions, is linked to increased white matter hyperintensities in the brain, pointing to possible vascular damage from repeated head trauma. However, the study results also show sparring was associated with a larger bilateral caudate which, in theory, is neuroprotective.

“From our preliminary study, sparring practice in MMA fighters may have a ‘double-edged sword’ effect on the brain,” study investigator Aaron Esagoff, a second-year medical student at Johns Hopkins University School of Medicine, Baltimore, told this news organization.

Growing popularity

MMA is a full-contact combat sport that has become increasingly popular over the past 15 years. It combines techniques from boxing, wrestling, karate, judo, and jujitsu.

To prepare for fights, MMA practitioners incorporate sparring and grappling, which use techniques such as chokes and locks to submit an opponent. Head protection is sometimes incorporated during practice, but is not the norm during a fight, said Mr. Esagoff.

The study investigated sparring during practice rather than fights because, he said, MMA competitors only fight a few times a year but spend hundreds of hours training. “So the health effects of training are going to be really important,” he said.

As with other combat sports, MMA involves hits to the head. Previous research has shown repetitive head trauma can lead to neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Alzheimer’s disease, Mr. Esagoff noted.

Previous studies have also linked more professional fights and years of fighting to a decrease in brain volume among MMA fighters, he added.

The new analysis was conducted as part of the Professional Fighters Brain Health Study, a longitudinal cohort study of MMA professional fighters. It included 92 fighters with data available on MRI and habits regarding practicing. The mean age of the participants was 30 years, 62% were White, and 85% were men.

The study examined sparring but did not include grappling because of “several challenges” with the current data analysis, Mr. Esagoff said. Researchers adjusted for age, sex, education, race, number of fights, total intracranial volume, and type of MRI scanner used.
 

A ‘highly strategic’ sport

Results showed a strong association between the number of sparring rounds per week and increased white matter hyperintensity volume (mcL) on MRI (P = .039).

This suggests white matter damage, possibly a result of direct neuronal injury, vascular damage, or immune modulation, said Mr. Esagoff. However, another mechanism may be involved, he added.

There was also a significant association between sparring and increased size of the caudate nucleus, an area of the brain involved in movement, learning, and memory (P = .014 for right caudate volume, P = .012 for left caudate volume).

There are some theories that might explain this finding, said Mr. Esagoff. For example, individuals who spar more may get better at avoiding impacts and injuries during a fight, which might in turn affect the size of the caudate.

The controlled movements and techniques used during sparring could also affect the caudate. “Some research has shown that behavior, learning, and/or exercise may increase the size of certain brain regions,” Mr. Esagoff said.

He noted the “highly strategic” nature of combat sports – and used the example of Brazilian jiu-jitsu. That sport “is known as human chess because it takes a thoughtful approach to defeat a larger opponent with base, leverage, and technique,” he said.

However, Mr. Esagoff stressed that while it is possible movements involved in MMA increase caudate size, this is just a theory at this point.

A study limitation was that fighters volunteered to participate and may not represent all fighters. As well, the study was cross-sectional and looked at only one point in time, so it cannot infer causation.

Overall, the new findings should help inform fighters, governing bodies, and the public about the potential risks and benefits of different styles of MMA fighting and practice, although more research is needed, said Mr. Esagoff.

He and his team now plan to conduct a longer-term study and investigate effects of grappling on brain structure and function in addition to sparring.
 

Jury still out

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry and incoming chair of the APA’s Council on Communications, said the jury “is clearly still out” when it comes to the investigation of brain impacts.

“We don’t know quite what these changes fully correlate to,” said Dr. Liu, who moderated a press briefing highlighting the study.

He underlined the importance of protecting athletes vulnerable to head trauma, be they professionals or those involved at the youth sports level.

Dr. Liu also noted the “extreme popularity” and rapid growth of MMA around the world, which he said provides an opportunity for researchers to study these professional fighters.

“This is a unique population that signed up in the midst of hundreds of hours of sparring to advance neuroscience, and that’s quite amazing,” he said.

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

The U.S. Food and Drug Administration is easing rules to allow infant formula imports from the United Kingdom, which would bring about 2 million cans to the U.S. in coming weeks.

Kendal Nutricare will be able to offer certain infant formula products under the Kendamil brand to ease the nationwide formula shortage.

“Importantly, we anticipate additional infant formula products may be safely and quickly imported in the U.S. in the near-term, based on ongoing discussions with manufacturers and suppliers worldwide,” Robert Califf, MD, the FDA commissioner, said in a statement.

Kendal Nutricare has more than 40,000 cans in stock for immediate dispatch, the FDA said, and the U.S. Department of Health and Human Services is talking to the company about the best ways to get the products to the U.S. as quickly as possible.

Kendamil has set up a website for consumers to receive updates and find products once they arrive in the U.S.

After an evaluation, the FDA said it had no safety or nutrition concerns about the products. The evaluation reviewed the company’s microbiological testing, labeling, and information about facility production and inspection history.

On May 24, the FDA announced that Abbott Nutrition will release about 300,000 cans of its EleCare specialty amino acid-based formula to families that need urgent, life-sustaining supplies. The products had more tests for microbes before release.

Although some EleCare products were included in Abbott’s infant formula recall earlier this year, the cans that will be released were in different lots, have never been released, and have been maintained in storage, the FDA said.

“These EleCare product lots were not part of the recall but have been on hold due to concerns that they were produced under unsanitary conditions observed at Abbott Nutrition’s Sturgis, Michigan, facility,” the FDA wrote.

The FDA encourages parents and caregivers to talk with their health care providers to weigh the potential risk of bacterial infection with the critical need for the product, based on its special dietary formulation for infants with severe food allergies or gut disorders.

The FDA also said that Abbott confirmed the EleCare products will be the first formula produced at the Sturgis facility when it restarts production soon. Other specialty metabolic formulas will follow.

Abbott plans to restart production at the Sturgis facility on June 4, the company said in a statement, noting that the early batches of EleCare would be available to consumers around June 20.

The products being released now are EleCare (for infants under 1 year) and EleCare Jr. (for ages 1 and older). Those who want to request products should contact their health care providers or call Abbott directly at 800-881-0876.

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

The U.S. Food and Drug Administration is easing rules to allow infant formula imports from the United Kingdom, which would bring about 2 million cans to the U.S. in coming weeks.

Kendal Nutricare will be able to offer certain infant formula products under the Kendamil brand to ease the nationwide formula shortage.

“Importantly, we anticipate additional infant formula products may be safely and quickly imported in the U.S. in the near-term, based on ongoing discussions with manufacturers and suppliers worldwide,” Robert Califf, MD, the FDA commissioner, said in a statement.

Kendal Nutricare has more than 40,000 cans in stock for immediate dispatch, the FDA said, and the U.S. Department of Health and Human Services is talking to the company about the best ways to get the products to the U.S. as quickly as possible.

Kendamil has set up a website for consumers to receive updates and find products once they arrive in the U.S.

After an evaluation, the FDA said it had no safety or nutrition concerns about the products. The evaluation reviewed the company’s microbiological testing, labeling, and information about facility production and inspection history.

On May 24, the FDA announced that Abbott Nutrition will release about 300,000 cans of its EleCare specialty amino acid-based formula to families that need urgent, life-sustaining supplies. The products had more tests for microbes before release.

Although some EleCare products were included in Abbott’s infant formula recall earlier this year, the cans that will be released were in different lots, have never been released, and have been maintained in storage, the FDA said.

“These EleCare product lots were not part of the recall but have been on hold due to concerns that they were produced under unsanitary conditions observed at Abbott Nutrition’s Sturgis, Michigan, facility,” the FDA wrote.

The FDA encourages parents and caregivers to talk with their health care providers to weigh the potential risk of bacterial infection with the critical need for the product, based on its special dietary formulation for infants with severe food allergies or gut disorders.

The FDA also said that Abbott confirmed the EleCare products will be the first formula produced at the Sturgis facility when it restarts production soon. Other specialty metabolic formulas will follow.

Abbott plans to restart production at the Sturgis facility on June 4, the company said in a statement, noting that the early batches of EleCare would be available to consumers around June 20.

The products being released now are EleCare (for infants under 1 year) and EleCare Jr. (for ages 1 and older). Those who want to request products should contact their health care providers or call Abbott directly at 800-881-0876.

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

The U.S. Food and Drug Administration is easing rules to allow infant formula imports from the United Kingdom, which would bring about 2 million cans to the U.S. in coming weeks.

Kendal Nutricare will be able to offer certain infant formula products under the Kendamil brand to ease the nationwide formula shortage.

“Importantly, we anticipate additional infant formula products may be safely and quickly imported in the U.S. in the near-term, based on ongoing discussions with manufacturers and suppliers worldwide,” Robert Califf, MD, the FDA commissioner, said in a statement.

Kendal Nutricare has more than 40,000 cans in stock for immediate dispatch, the FDA said, and the U.S. Department of Health and Human Services is talking to the company about the best ways to get the products to the U.S. as quickly as possible.

Kendamil has set up a website for consumers to receive updates and find products once they arrive in the U.S.

After an evaluation, the FDA said it had no safety or nutrition concerns about the products. The evaluation reviewed the company’s microbiological testing, labeling, and information about facility production and inspection history.

On May 24, the FDA announced that Abbott Nutrition will release about 300,000 cans of its EleCare specialty amino acid-based formula to families that need urgent, life-sustaining supplies. The products had more tests for microbes before release.

Although some EleCare products were included in Abbott’s infant formula recall earlier this year, the cans that will be released were in different lots, have never been released, and have been maintained in storage, the FDA said.

“These EleCare product lots were not part of the recall but have been on hold due to concerns that they were produced under unsanitary conditions observed at Abbott Nutrition’s Sturgis, Michigan, facility,” the FDA wrote.

The FDA encourages parents and caregivers to talk with their health care providers to weigh the potential risk of bacterial infection with the critical need for the product, based on its special dietary formulation for infants with severe food allergies or gut disorders.

The FDA also said that Abbott confirmed the EleCare products will be the first formula produced at the Sturgis facility when it restarts production soon. Other specialty metabolic formulas will follow.

Abbott plans to restart production at the Sturgis facility on June 4, the company said in a statement, noting that the early batches of EleCare would be available to consumers around June 20.

The products being released now are EleCare (for infants under 1 year) and EleCare Jr. (for ages 1 and older). Those who want to request products should contact their health care providers or call Abbott directly at 800-881-0876.

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

A limited association exists between the use of isotretinoin for severe acne and worsening of a patient’s baseline inflammatory bowel disease, results from a small retrospective study suggests.

“Early studies of isotretinoin for use in severe acne suggested the drug may serve as a trigger for new-onset inflammatory bowel disease (IBD),” researchers led by Christina G. Lopez, MD, of the Lewis Katz School of Medicine at Temple University, Philadelphia, wrote in an article published online , in the Journal of the American Academy of Dermatology. “While more recent studies have suggested no such causal relationship, little is known about the medication’s effect on patients with a preexisting IBD diagnosis.”

To investigate this topic further, the researchers identified 19 patients who were diagnosed with IBD and treated with isotretinoin between Jan. 1, 2006, and Jan. 1, 2020, at Mass General Brigham Hospitals, Boston. They determined severity of disease and degree of antecedent management of IBD by evaluating flaring two years prior to starting isotretinoin. The patients were considered to have a flare caused by isotretinoin if the IBD flare occurred during or up to 3 months following course completion.

The mean age of the 19 patients was 35 years, 26% were female, and 95% were White. Nearly half of the patients (42%) had ulcerative colitis, 37% had Crohn’s disease, and 21% had both. The researchers found that nine patients had flared two years before starting isotretinoin. Of these, five (56%) flared and four (44%) did not flare during treatment or within three months of completing the course of isotretinoin.

Of the 10 patients who did not flare two years before starting isotretinoin, seven (70%) did not flare during treatment and three (30%) flared during or within three months following completion of isotretinoin use. The researchers found no statistically significant association between isotretinoin use and flaring among patients with IBD (P = .76).

Dr. Lopez and her colleagues also assessed IBD maintenance therapy with respect to IBD flares in the study population. They observed no statistically significant association between the use of maintenance IBD therapy and the likelihood of having flares during isotretinoin treatment (P = .15).

“The results suggest limited association between isotretinoin and the worsening of a patient’s baseline IBD,” the authors concluded. They acknowledged certain limitations of the study, including its small sample size and retrospective design, and they called for larger and prospective studies to assess the relationship of IBD flaring in this population of patients.

Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, who was asked to comment on the results, characterized the trial as “an important study highlighting how we continue to understand the safe use of isotretinoin in the IBD cohort.”

Isotretinoin, she added, “continues to be a highly important treatment for acne and in patients such as these where oral antibiotics are relatively contraindicated due to risk of exacerbating their bowel disease.” Such data are reassuring, “albeit future studies with larger patient pools are desirable,” she added. “Future studies could also help to elucidate if diet, smoking, sleep, exercise, and medication adherence are potential confounding factors along with whether the cumulative isotretinoin dose has any effect on IBD flares in those who are susceptible.”

Neither the researchers nor Dr. Sodha had financial conflicts. The other authors were from Brigham and Women’s Hospital, Harvard University, Boston, and the University of Massachusetts, Worcester.

A limited association exists between the use of isotretinoin for severe acne and worsening of a patient’s baseline inflammatory bowel disease, results from a small retrospective study suggests.

“Early studies of isotretinoin for use in severe acne suggested the drug may serve as a trigger for new-onset inflammatory bowel disease (IBD),” researchers led by Christina G. Lopez, MD, of the Lewis Katz School of Medicine at Temple University, Philadelphia, wrote in an article published online , in the Journal of the American Academy of Dermatology. “While more recent studies have suggested no such causal relationship, little is known about the medication’s effect on patients with a preexisting IBD diagnosis.”

To investigate this topic further, the researchers identified 19 patients who were diagnosed with IBD and treated with isotretinoin between Jan. 1, 2006, and Jan. 1, 2020, at Mass General Brigham Hospitals, Boston. They determined severity of disease and degree of antecedent management of IBD by evaluating flaring two years prior to starting isotretinoin. The patients were considered to have a flare caused by isotretinoin if the IBD flare occurred during or up to 3 months following course completion.

The mean age of the 19 patients was 35 years, 26% were female, and 95% were White. Nearly half of the patients (42%) had ulcerative colitis, 37% had Crohn’s disease, and 21% had both. The researchers found that nine patients had flared two years before starting isotretinoin. Of these, five (56%) flared and four (44%) did not flare during treatment or within three months of completing the course of isotretinoin.

Of the 10 patients who did not flare two years before starting isotretinoin, seven (70%) did not flare during treatment and three (30%) flared during or within three months following completion of isotretinoin use. The researchers found no statistically significant association between isotretinoin use and flaring among patients with IBD (P = .76).

Dr. Lopez and her colleagues also assessed IBD maintenance therapy with respect to IBD flares in the study population. They observed no statistically significant association between the use of maintenance IBD therapy and the likelihood of having flares during isotretinoin treatment (P = .15).

“The results suggest limited association between isotretinoin and the worsening of a patient’s baseline IBD,” the authors concluded. They acknowledged certain limitations of the study, including its small sample size and retrospective design, and they called for larger and prospective studies to assess the relationship of IBD flaring in this population of patients.

Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, who was asked to comment on the results, characterized the trial as “an important study highlighting how we continue to understand the safe use of isotretinoin in the IBD cohort.”

Isotretinoin, she added, “continues to be a highly important treatment for acne and in patients such as these where oral antibiotics are relatively contraindicated due to risk of exacerbating their bowel disease.” Such data are reassuring, “albeit future studies with larger patient pools are desirable,” she added. “Future studies could also help to elucidate if diet, smoking, sleep, exercise, and medication adherence are potential confounding factors along with whether the cumulative isotretinoin dose has any effect on IBD flares in those who are susceptible.”

Neither the researchers nor Dr. Sodha had financial conflicts. The other authors were from Brigham and Women’s Hospital, Harvard University, Boston, and the University of Massachusetts, Worcester.

A limited association exists between the use of isotretinoin for severe acne and worsening of a patient’s baseline inflammatory bowel disease, results from a small retrospective study suggests.

“Early studies of isotretinoin for use in severe acne suggested the drug may serve as a trigger for new-onset inflammatory bowel disease (IBD),” researchers led by Christina G. Lopez, MD, of the Lewis Katz School of Medicine at Temple University, Philadelphia, wrote in an article published online , in the Journal of the American Academy of Dermatology. “While more recent studies have suggested no such causal relationship, little is known about the medication’s effect on patients with a preexisting IBD diagnosis.”

To investigate this topic further, the researchers identified 19 patients who were diagnosed with IBD and treated with isotretinoin between Jan. 1, 2006, and Jan. 1, 2020, at Mass General Brigham Hospitals, Boston. They determined severity of disease and degree of antecedent management of IBD by evaluating flaring two years prior to starting isotretinoin. The patients were considered to have a flare caused by isotretinoin if the IBD flare occurred during or up to 3 months following course completion.

The mean age of the 19 patients was 35 years, 26% were female, and 95% were White. Nearly half of the patients (42%) had ulcerative colitis, 37% had Crohn’s disease, and 21% had both. The researchers found that nine patients had flared two years before starting isotretinoin. Of these, five (56%) flared and four (44%) did not flare during treatment or within three months of completing the course of isotretinoin.

Of the 10 patients who did not flare two years before starting isotretinoin, seven (70%) did not flare during treatment and three (30%) flared during or within three months following completion of isotretinoin use. The researchers found no statistically significant association between isotretinoin use and flaring among patients with IBD (P = .76).

Dr. Lopez and her colleagues also assessed IBD maintenance therapy with respect to IBD flares in the study population. They observed no statistically significant association between the use of maintenance IBD therapy and the likelihood of having flares during isotretinoin treatment (P = .15).

“The results suggest limited association between isotretinoin and the worsening of a patient’s baseline IBD,” the authors concluded. They acknowledged certain limitations of the study, including its small sample size and retrospective design, and they called for larger and prospective studies to assess the relationship of IBD flaring in this population of patients.

Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington, who was asked to comment on the results, characterized the trial as “an important study highlighting how we continue to understand the safe use of isotretinoin in the IBD cohort.”

Isotretinoin, she added, “continues to be a highly important treatment for acne and in patients such as these where oral antibiotics are relatively contraindicated due to risk of exacerbating their bowel disease.” Such data are reassuring, “albeit future studies with larger patient pools are desirable,” she added. “Future studies could also help to elucidate if diet, smoking, sleep, exercise, and medication adherence are potential confounding factors along with whether the cumulative isotretinoin dose has any effect on IBD flares in those who are susceptible.”

Neither the researchers nor Dr. Sodha had financial conflicts. The other authors were from Brigham and Women’s Hospital, Harvard University, Boston, and the University of Massachusetts, Worcester.

As the parents of the 19 children shot dead Tuesday in Uvalde, Tex., by a teen gunman grapple with unspeakable grief and funeral preparations, the survivors and their families are dealing with their own angst and likely much more.

While the parents understandably feel lucky that their children made it out, what about the long-term effect on their children of witnessing that carnage, of seeing classmates, friends, and teachers die violently as they stood by helpless and fearful?

The outcome over the next few days, months, and years depends on many factors, but how parents address the trauma both immediately and long-term can make a huge difference, experts say.
 

Posttraumatic growth

Best long-term case scenario? Survivors can experience what experts call posttraumatic growth – reaching out to give back to society, to make the world a better place, and changing who they are and their view of the world.

A prime example of posttraumatic growth: A month after a teen gunman killed 17 students at Marjory Stoneman Douglas High School in Parkland, Fla., on Valentine’s Day 2018, an army of survivors from that day’s bloodbath headed to Washington, D.C., for the now-famous March for Our Lives. The student-led demonstration, with hundreds of thousands of supporters marching, called for gun control legislation and an end to gun violence. It remains a vibrant, nonprofit organization still advocating for universal background checks and increased support of mental health services.
 

No sign of future violence

While most children and teens who witness school violence won’t become high-profile activists, as survivors of Parkland and the numerous other school shootings have, neither will they become the next active shooter, mental health experts say. They can’t point to a study that follows the gun violence victims that shows who does OK and who doesn’t, but they know immediate support and therapy can go a long way to recovery.

“I can’t tell you how any particular child will do,” says Robin Gurwitch, PhD, psychologist and professor at Duke University Medical Center, Durham, N.C. “I can tell you the majority of kids will be OK.”

However, that doesn’t mean a surviving child won’t have behavior and other issues, she says. Research does suggest the next few days, weeks, or months will be rough.

What parents and other caretakers do in the days after the violence will help predict the long-term outcome. Dr. Gurwitch and other experts say it’s important to first focus on what they call “psychological first aid,” then phase in therapy such as trauma-focused cognitive behavioral therapy, if and when it’s needed.
 

First, ‘psychological first aid’

“Psychological first aid is designed to minimize the impact down the road,” Dr. Gurwitch says. “Validate that they are feeling scared or worried.”

Some may be angry, another understandable emotion. In the first few days of witnessing violence – or even just hearing about it – parents should expect clinginess, sleep problems, behavior meltdowns, and irritability, she says.

“Those kinds of changes are likely to last a few weeks,” she says.

If day-to-day functioning is very difficult, “don’t wait for those to pass,” Dr. Gurwitch says. “Reach out for help. Resources will be available. Check with your pediatrician or family physician.”

At home, parents can address specific problems related to the experience, Dr. Gurwitch says. If it’s sleep, she says, parents and kids can work together to figure out how to ease sleep, such as listening to their favorite music before bedtime.

While parents may be inclined to baby the kids after the violence, Dr. Gurwitch says it’s important to maintain routines. So it’s not cruel to insist they do their chores.
 

Expect change

Things won’t be the same.

“Anytime we go through a particular traumatic event, we are changed,” Dr. Gurwitch says. ‘’The question is, what do we do about it? How do we incorporate that change into who we are and have become?”

Also important is figuring out how to make meaning out of what happened.

“I am so impressed by the families at Sandy Hook (the Connecticut elementary school where a gunman killed 26 in 2012),” she says.

They set up foundations and did other advocacy work.

“These types of events are life-changing events,” agrees David Schonfeld, MD, a pediatrician and director of the National Center for Schools Crisis and Bereavement at Children’s Hospital Los Angeles, California. “They will change who children are as people, but it doesn’t mean they are damaged for life. They will remember it as long as they live, and it will also change who they are as a person.”

While people tend to stress the potential negative effects – and there certainly are some – ‘’some individuals actually emerge from these events with a renewed sense of purpose.’’

He tells parents: “Yes, your child has changed, and you can’t go back. But it doesn’t mean they are destined to never be able to cope [with trauma].”
 

Research

The effects of gun violence on children can be serious and dramatic, research shows.

• Exposure to neighborhood gun violence is linked with an increase in children’s mental health issues,  have found. Children living within two or three blocks of gun violence had nearly twice the risk of going to the emergency department with a mental health complaint in the 14 days following the shooting.  
• Exposure to gun violence should be classified, along with maltreatment, household dysfunction, and other issues known to impact children negatively, as an adverse childhood experience, other experts 
• Direct gun violence exposure, witnessing it, and hearing gunshots are all associated with children being victimized in other ways, another  found. And that poly-victimization, as it is called, was strongly associated with having posttraumatic symptoms.

Adverse Childhood Events, as these sorts of experiences are known, can have long-lasting effects on physical and mental health, as well as on even the economic future of a person, says Hansa Bhargava, MD, a pediatrician and chief medical officer of Medscape, WebMD’s sister site for medical professionals.

“Kids who have suffered through violent events can have brain development affected, as well as their immune systems,” she says. “They are more likely to have chronic disease, substance use disorder, sexually transmitted diseases, teen pregnancy, and lifelong depression. A high risk of [posttraumatic stress disorder] is likely for them and their families.”
 

The impact of family support

The gun violence and deaths are likely to remind children of other losses they have experienced, Dr. Schonfeld says, and that can make coping more difficult.

If the trauma from the Tuesday shootings is ‘’layered” on top of trauma from COVID-19 deaths or other trauma such as domestic violence, those children may have a more difficult time, says Allan Chrisman, MD, professor emeritus of psychiatry and behavioral sciences at Duke University Health System. However, protective factors such as the family response and the community response can build resilience in survivors, he says.

“The way in which parents handle it for themselves will have a huge impact on the kids,” Dr. Chrisman says. “The worst outcomes are linked with [parents saying], ‘We don’t want to talk about it.’ ”

The parents are understandably upset, Dr. Gurwitch says. It’s OK to show sadness, anger, and other emotions, but she tells parents: “It’s not OK to completely decompose.” It’s important for the children to see that parents can pull themselves together.
 

Longer-term effects

As time goes on, ‘’a very large percentage will have posttraumatic reactions,” Dr. Schonfeld says. “Those reactions tend to improve over time.”

While people talk about PTSD directly after an incident such as a school shooting, it isn’t officially diagnosed as PTSD until the symptoms describing PTSD have persisted for a month, Dr. Schonfeld says. However, ‘’that doesn’t mean you don’t have a problem” that needs attention from a mental health professional.

“As a country we are already struggling with a mental health crisis,” Dr. Bhargava says. “Events such as this serve to exacerbate even more crisis in a group of innocent children whose only crime was to attend school. We must address the ‘epidemic’ of gun violence and school shootings head on. For the sake of our children and their health. For all of us.”
 

Therapy that works

Cognitive behavioral therapy (CBT) approaches are effective in reducing the trauma, Dr. Gurwitch says.

She often recommends one type of CBT, called trauma-focused cognitive behavioral therapy. This approach involves children and parents and focuses on safety, coping skills, and gradual exposure. It’s a structured and short-term treatment of about eight to 25 sessions.

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

As the parents of the 19 children shot dead Tuesday in Uvalde, Tex., by a teen gunman grapple with unspeakable grief and funeral preparations, the survivors and their families are dealing with their own angst and likely much more.

While the parents understandably feel lucky that their children made it out, what about the long-term effect on their children of witnessing that carnage, of seeing classmates, friends, and teachers die violently as they stood by helpless and fearful?

The outcome over the next few days, months, and years depends on many factors, but how parents address the trauma both immediately and long-term can make a huge difference, experts say.
 

Posttraumatic growth

Best long-term case scenario? Survivors can experience what experts call posttraumatic growth – reaching out to give back to society, to make the world a better place, and changing who they are and their view of the world.

A prime example of posttraumatic growth: A month after a teen gunman killed 17 students at Marjory Stoneman Douglas High School in Parkland, Fla., on Valentine’s Day 2018, an army of survivors from that day’s bloodbath headed to Washington, D.C., for the now-famous March for Our Lives. The student-led demonstration, with hundreds of thousands of supporters marching, called for gun control legislation and an end to gun violence. It remains a vibrant, nonprofit organization still advocating for universal background checks and increased support of mental health services.
 

No sign of future violence

While most children and teens who witness school violence won’t become high-profile activists, as survivors of Parkland and the numerous other school shootings have, neither will they become the next active shooter, mental health experts say. They can’t point to a study that follows the gun violence victims that shows who does OK and who doesn’t, but they know immediate support and therapy can go a long way to recovery.

“I can’t tell you how any particular child will do,” says Robin Gurwitch, PhD, psychologist and professor at Duke University Medical Center, Durham, N.C. “I can tell you the majority of kids will be OK.”

However, that doesn’t mean a surviving child won’t have behavior and other issues, she says. Research does suggest the next few days, weeks, or months will be rough.

What parents and other caretakers do in the days after the violence will help predict the long-term outcome. Dr. Gurwitch and other experts say it’s important to first focus on what they call “psychological first aid,” then phase in therapy such as trauma-focused cognitive behavioral therapy, if and when it’s needed.
 

First, ‘psychological first aid’

“Psychological first aid is designed to minimize the impact down the road,” Dr. Gurwitch says. “Validate that they are feeling scared or worried.”

Some may be angry, another understandable emotion. In the first few days of witnessing violence – or even just hearing about it – parents should expect clinginess, sleep problems, behavior meltdowns, and irritability, she says.

“Those kinds of changes are likely to last a few weeks,” she says.

If day-to-day functioning is very difficult, “don’t wait for those to pass,” Dr. Gurwitch says. “Reach out for help. Resources will be available. Check with your pediatrician or family physician.”

At home, parents can address specific problems related to the experience, Dr. Gurwitch says. If it’s sleep, she says, parents and kids can work together to figure out how to ease sleep, such as listening to their favorite music before bedtime.

While parents may be inclined to baby the kids after the violence, Dr. Gurwitch says it’s important to maintain routines. So it’s not cruel to insist they do their chores.
 

Expect change

Things won’t be the same.

“Anytime we go through a particular traumatic event, we are changed,” Dr. Gurwitch says. ‘’The question is, what do we do about it? How do we incorporate that change into who we are and have become?”

Also important is figuring out how to make meaning out of what happened.

“I am so impressed by the families at Sandy Hook (the Connecticut elementary school where a gunman killed 26 in 2012),” she says.

They set up foundations and did other advocacy work.

“These types of events are life-changing events,” agrees David Schonfeld, MD, a pediatrician and director of the National Center for Schools Crisis and Bereavement at Children’s Hospital Los Angeles, California. “They will change who children are as people, but it doesn’t mean they are damaged for life. They will remember it as long as they live, and it will also change who they are as a person.”

While people tend to stress the potential negative effects – and there certainly are some – ‘’some individuals actually emerge from these events with a renewed sense of purpose.’’

He tells parents: “Yes, your child has changed, and you can’t go back. But it doesn’t mean they are destined to never be able to cope [with trauma].”
 

Research

The effects of gun violence on children can be serious and dramatic, research shows.

• Exposure to neighborhood gun violence is linked with an increase in children’s mental health issues,  have found. Children living within two or three blocks of gun violence had nearly twice the risk of going to the emergency department with a mental health complaint in the 14 days following the shooting.  
• Exposure to gun violence should be classified, along with maltreatment, household dysfunction, and other issues known to impact children negatively, as an adverse childhood experience, other experts 
• Direct gun violence exposure, witnessing it, and hearing gunshots are all associated with children being victimized in other ways, another  found. And that poly-victimization, as it is called, was strongly associated with having posttraumatic symptoms.

Adverse Childhood Events, as these sorts of experiences are known, can have long-lasting effects on physical and mental health, as well as on even the economic future of a person, says Hansa Bhargava, MD, a pediatrician and chief medical officer of Medscape, WebMD’s sister site for medical professionals.

“Kids who have suffered through violent events can have brain development affected, as well as their immune systems,” she says. “They are more likely to have chronic disease, substance use disorder, sexually transmitted diseases, teen pregnancy, and lifelong depression. A high risk of [posttraumatic stress disorder] is likely for them and their families.”
 

The impact of family support

The gun violence and deaths are likely to remind children of other losses they have experienced, Dr. Schonfeld says, and that can make coping more difficult.

If the trauma from the Tuesday shootings is ‘’layered” on top of trauma from COVID-19 deaths or other trauma such as domestic violence, those children may have a more difficult time, says Allan Chrisman, MD, professor emeritus of psychiatry and behavioral sciences at Duke University Health System. However, protective factors such as the family response and the community response can build resilience in survivors, he says.

“The way in which parents handle it for themselves will have a huge impact on the kids,” Dr. Chrisman says. “The worst outcomes are linked with [parents saying], ‘We don’t want to talk about it.’ ”

The parents are understandably upset, Dr. Gurwitch says. It’s OK to show sadness, anger, and other emotions, but she tells parents: “It’s not OK to completely decompose.” It’s important for the children to see that parents can pull themselves together.
 

Longer-term effects

As time goes on, ‘’a very large percentage will have posttraumatic reactions,” Dr. Schonfeld says. “Those reactions tend to improve over time.”

While people talk about PTSD directly after an incident such as a school shooting, it isn’t officially diagnosed as PTSD until the symptoms describing PTSD have persisted for a month, Dr. Schonfeld says. However, ‘’that doesn’t mean you don’t have a problem” that needs attention from a mental health professional.

“As a country we are already struggling with a mental health crisis,” Dr. Bhargava says. “Events such as this serve to exacerbate even more crisis in a group of innocent children whose only crime was to attend school. We must address the ‘epidemic’ of gun violence and school shootings head on. For the sake of our children and their health. For all of us.”
 

Therapy that works

Cognitive behavioral therapy (CBT) approaches are effective in reducing the trauma, Dr. Gurwitch says.

She often recommends one type of CBT, called trauma-focused cognitive behavioral therapy. This approach involves children and parents and focuses on safety, coping skills, and gradual exposure. It’s a structured and short-term treatment of about eight to 25 sessions.

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

As the parents of the 19 children shot dead Tuesday in Uvalde, Tex., by a teen gunman grapple with unspeakable grief and funeral preparations, the survivors and their families are dealing with their own angst and likely much more.

While the parents understandably feel lucky that their children made it out, what about the long-term effect on their children of witnessing that carnage, of seeing classmates, friends, and teachers die violently as they stood by helpless and fearful?

The outcome over the next few days, months, and years depends on many factors, but how parents address the trauma both immediately and long-term can make a huge difference, experts say.
 

Posttraumatic growth

Best long-term case scenario? Survivors can experience what experts call posttraumatic growth – reaching out to give back to society, to make the world a better place, and changing who they are and their view of the world.

A prime example of posttraumatic growth: A month after a teen gunman killed 17 students at Marjory Stoneman Douglas High School in Parkland, Fla., on Valentine’s Day 2018, an army of survivors from that day’s bloodbath headed to Washington, D.C., for the now-famous March for Our Lives. The student-led demonstration, with hundreds of thousands of supporters marching, called for gun control legislation and an end to gun violence. It remains a vibrant, nonprofit organization still advocating for universal background checks and increased support of mental health services.
 

No sign of future violence

While most children and teens who witness school violence won’t become high-profile activists, as survivors of Parkland and the numerous other school shootings have, neither will they become the next active shooter, mental health experts say. They can’t point to a study that follows the gun violence victims that shows who does OK and who doesn’t, but they know immediate support and therapy can go a long way to recovery.

“I can’t tell you how any particular child will do,” says Robin Gurwitch, PhD, psychologist and professor at Duke University Medical Center, Durham, N.C. “I can tell you the majority of kids will be OK.”

However, that doesn’t mean a surviving child won’t have behavior and other issues, she says. Research does suggest the next few days, weeks, or months will be rough.

What parents and other caretakers do in the days after the violence will help predict the long-term outcome. Dr. Gurwitch and other experts say it’s important to first focus on what they call “psychological first aid,” then phase in therapy such as trauma-focused cognitive behavioral therapy, if and when it’s needed.
 

First, ‘psychological first aid’

“Psychological first aid is designed to minimize the impact down the road,” Dr. Gurwitch says. “Validate that they are feeling scared or worried.”

Some may be angry, another understandable emotion. In the first few days of witnessing violence – or even just hearing about it – parents should expect clinginess, sleep problems, behavior meltdowns, and irritability, she says.

“Those kinds of changes are likely to last a few weeks,” she says.

If day-to-day functioning is very difficult, “don’t wait for those to pass,” Dr. Gurwitch says. “Reach out for help. Resources will be available. Check with your pediatrician or family physician.”

At home, parents can address specific problems related to the experience, Dr. Gurwitch says. If it’s sleep, she says, parents and kids can work together to figure out how to ease sleep, such as listening to their favorite music before bedtime.

While parents may be inclined to baby the kids after the violence, Dr. Gurwitch says it’s important to maintain routines. So it’s not cruel to insist they do their chores.
 

Expect change

Things won’t be the same.

“Anytime we go through a particular traumatic event, we are changed,” Dr. Gurwitch says. ‘’The question is, what do we do about it? How do we incorporate that change into who we are and have become?”

Also important is figuring out how to make meaning out of what happened.

“I am so impressed by the families at Sandy Hook (the Connecticut elementary school where a gunman killed 26 in 2012),” she says.

They set up foundations and did other advocacy work.

“These types of events are life-changing events,” agrees David Schonfeld, MD, a pediatrician and director of the National Center for Schools Crisis and Bereavement at Children’s Hospital Los Angeles, California. “They will change who children are as people, but it doesn’t mean they are damaged for life. They will remember it as long as they live, and it will also change who they are as a person.”

While people tend to stress the potential negative effects – and there certainly are some – ‘’some individuals actually emerge from these events with a renewed sense of purpose.’’

He tells parents: “Yes, your child has changed, and you can’t go back. But it doesn’t mean they are destined to never be able to cope [with trauma].”
 

Research

The effects of gun violence on children can be serious and dramatic, research shows.

• Exposure to neighborhood gun violence is linked with an increase in children’s mental health issues,  have found. Children living within two or three blocks of gun violence had nearly twice the risk of going to the emergency department with a mental health complaint in the 14 days following the shooting.  
• Exposure to gun violence should be classified, along with maltreatment, household dysfunction, and other issues known to impact children negatively, as an adverse childhood experience, other experts 
• Direct gun violence exposure, witnessing it, and hearing gunshots are all associated with children being victimized in other ways, another  found. And that poly-victimization, as it is called, was strongly associated with having posttraumatic symptoms.

Adverse Childhood Events, as these sorts of experiences are known, can have long-lasting effects on physical and mental health, as well as on even the economic future of a person, says Hansa Bhargava, MD, a pediatrician and chief medical officer of Medscape, WebMD’s sister site for medical professionals.

“Kids who have suffered through violent events can have brain development affected, as well as their immune systems,” she says. “They are more likely to have chronic disease, substance use disorder, sexually transmitted diseases, teen pregnancy, and lifelong depression. A high risk of [posttraumatic stress disorder] is likely for them and their families.”
 

The impact of family support

The gun violence and deaths are likely to remind children of other losses they have experienced, Dr. Schonfeld says, and that can make coping more difficult.

If the trauma from the Tuesday shootings is ‘’layered” on top of trauma from COVID-19 deaths or other trauma such as domestic violence, those children may have a more difficult time, says Allan Chrisman, MD, professor emeritus of psychiatry and behavioral sciences at Duke University Health System. However, protective factors such as the family response and the community response can build resilience in survivors, he says.

“The way in which parents handle it for themselves will have a huge impact on the kids,” Dr. Chrisman says. “The worst outcomes are linked with [parents saying], ‘We don’t want to talk about it.’ ”

The parents are understandably upset, Dr. Gurwitch says. It’s OK to show sadness, anger, and other emotions, but she tells parents: “It’s not OK to completely decompose.” It’s important for the children to see that parents can pull themselves together.
 

Longer-term effects

As time goes on, ‘’a very large percentage will have posttraumatic reactions,” Dr. Schonfeld says. “Those reactions tend to improve over time.”

While people talk about PTSD directly after an incident such as a school shooting, it isn’t officially diagnosed as PTSD until the symptoms describing PTSD have persisted for a month, Dr. Schonfeld says. However, ‘’that doesn’t mean you don’t have a problem” that needs attention from a mental health professional.

“As a country we are already struggling with a mental health crisis,” Dr. Bhargava says. “Events such as this serve to exacerbate even more crisis in a group of innocent children whose only crime was to attend school. We must address the ‘epidemic’ of gun violence and school shootings head on. For the sake of our children and their health. For all of us.”
 

Therapy that works

Cognitive behavioral therapy (CBT) approaches are effective in reducing the trauma, Dr. Gurwitch says.

She often recommends one type of CBT, called trauma-focused cognitive behavioral therapy. This approach involves children and parents and focuses on safety, coping skills, and gradual exposure. It’s a structured and short-term treatment of about eight to 25 sessions.

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

On the basis of the patient's history and presentation, this is likely a case of adenocarcinoma of the prostate. Although most patients with prostate cancer are diagnosed on screening, when localized symptoms do occur, they may include urinary frequency, decreased urine stream, urinary urgency, and hematuria. In some cases, these signs and symptoms may well be related to age-associated prostate enlargement or other conditions; benign prostatic hyperplasia, for example, can manifest in urinary symptoms and even elevate PSA (but because this patient does not report pain, nonbacterial prostatitis is unlikely). Symptomatic patients older than 50 years, such as the one in this case, should be screened for prostate cancer. Those with a PSA > 10 ng/mL are more than 50% likely to have prostate cancer. 

National Comprehensive Cancer Network guidelines advise that needle biopsy of the prostate is indicated for tissue diagnosis in those with elevated PSA levels, preferably via a transrectal ultrasound. MRI can be used to assess lesions that are concerning for prostate cancer prior to biopsy. Lesions are then assigned Prostate Imaging Reporting and Data System (PI-RADS) scores depending on their location within the prostatic zones. A pathologic evaluation of the biopsy specimen will determine the patient's Gleason score. PSA density and PSA doubling time should be collected as well. The clinician should ask about high-risk germline mutations and estimate life expectancy because course of treatment is largely based on risk assessment.

Standard treatments for clinically localized prostate cancer include watchful waiting, active surveillance, radical prostatectomy, and radiation therapy. Active surveillance is often recommended for those who have very-low-risk disease because of the slow growth of certain types of prostate cancer. Radical prostatectomy is a viable option for any patient with localized disease that can be completely excised surgically, provided the patient has a life expectancy of 10 or more years and no serious comorbidities. In some patients, radical prostatectomy may be followed by radiation with or without a short course of hormone treatment, depending on risk factors for recurrence. Radiation therapy is also potentially curative in localized prostate cancer and may be delivered in the form of external-beam radiation therapy or brachytherapy. For asymptomatic patients who are older and/or have other serious underlying conditions, observation may be recommended.

Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Chad R. Tracy, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: CVICO Medical Solutions.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of the patient's history and presentation, this is likely a case of adenocarcinoma of the prostate. Although most patients with prostate cancer are diagnosed on screening, when localized symptoms do occur, they may include urinary frequency, decreased urine stream, urinary urgency, and hematuria. In some cases, these signs and symptoms may well be related to age-associated prostate enlargement or other conditions; benign prostatic hyperplasia, for example, can manifest in urinary symptoms and even elevate PSA (but because this patient does not report pain, nonbacterial prostatitis is unlikely). Symptomatic patients older than 50 years, such as the one in this case, should be screened for prostate cancer. Those with a PSA > 10 ng/mL are more than 50% likely to have prostate cancer. 

National Comprehensive Cancer Network guidelines advise that needle biopsy of the prostate is indicated for tissue diagnosis in those with elevated PSA levels, preferably via a transrectal ultrasound. MRI can be used to assess lesions that are concerning for prostate cancer prior to biopsy. Lesions are then assigned Prostate Imaging Reporting and Data System (PI-RADS) scores depending on their location within the prostatic zones. A pathologic evaluation of the biopsy specimen will determine the patient's Gleason score. PSA density and PSA doubling time should be collected as well. The clinician should ask about high-risk germline mutations and estimate life expectancy because course of treatment is largely based on risk assessment.

Standard treatments for clinically localized prostate cancer include watchful waiting, active surveillance, radical prostatectomy, and radiation therapy. Active surveillance is often recommended for those who have very-low-risk disease because of the slow growth of certain types of prostate cancer. Radical prostatectomy is a viable option for any patient with localized disease that can be completely excised surgically, provided the patient has a life expectancy of 10 or more years and no serious comorbidities. In some patients, radical prostatectomy may be followed by radiation with or without a short course of hormone treatment, depending on risk factors for recurrence. Radiation therapy is also potentially curative in localized prostate cancer and may be delivered in the form of external-beam radiation therapy or brachytherapy. For asymptomatic patients who are older and/or have other serious underlying conditions, observation may be recommended.

Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Chad R. Tracy, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: CVICO Medical Solutions.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

On the basis of the patient's history and presentation, this is likely a case of adenocarcinoma of the prostate. Although most patients with prostate cancer are diagnosed on screening, when localized symptoms do occur, they may include urinary frequency, decreased urine stream, urinary urgency, and hematuria. In some cases, these signs and symptoms may well be related to age-associated prostate enlargement or other conditions; benign prostatic hyperplasia, for example, can manifest in urinary symptoms and even elevate PSA (but because this patient does not report pain, nonbacterial prostatitis is unlikely). Symptomatic patients older than 50 years, such as the one in this case, should be screened for prostate cancer. Those with a PSA > 10 ng/mL are more than 50% likely to have prostate cancer. 

National Comprehensive Cancer Network guidelines advise that needle biopsy of the prostate is indicated for tissue diagnosis in those with elevated PSA levels, preferably via a transrectal ultrasound. MRI can be used to assess lesions that are concerning for prostate cancer prior to biopsy. Lesions are then assigned Prostate Imaging Reporting and Data System (PI-RADS) scores depending on their location within the prostatic zones. A pathologic evaluation of the biopsy specimen will determine the patient's Gleason score. PSA density and PSA doubling time should be collected as well. The clinician should ask about high-risk germline mutations and estimate life expectancy because course of treatment is largely based on risk assessment.

Standard treatments for clinically localized prostate cancer include watchful waiting, active surveillance, radical prostatectomy, and radiation therapy. Active surveillance is often recommended for those who have very-low-risk disease because of the slow growth of certain types of prostate cancer. Radical prostatectomy is a viable option for any patient with localized disease that can be completely excised surgically, provided the patient has a life expectancy of 10 or more years and no serious comorbidities. In some patients, radical prostatectomy may be followed by radiation with or without a short course of hormone treatment, depending on risk factors for recurrence. Radiation therapy is also potentially curative in localized prostate cancer and may be delivered in the form of external-beam radiation therapy or brachytherapy. For asymptomatic patients who are older and/or have other serious underlying conditions, observation may be recommended.

Chad R. Tracy, MD, Professor; Director, Minimally Invasive Surgery, Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, Iowa

Chad R. Tracy, MD, has disclosed the following relevant financial relationships:

Serve(d) as a consultant for: CVICO Medical Solutions.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The Safer Alternatives for Emergency Response (SAFER) program provides a safe supply of substances to prevent drug overdose deaths, according to a new report.

The program has been operating in Vancouver, British Columbia, since April 2021. So far, the program has enrolled 58 participants who have reported benefits from having new options when other forms of treatment or harm reduction didn’t work. In addition, doctors who work with the program have reported increased medication adherence among the participants, as well as better chronic disease management.

Similar safe supply programs are being implemented or considered in other places across Canada. Since 2019, Health Canada has funded 18 safe supply pilot programs.

“When we look at the number of overdose deaths, it should be zero. These are preventable deaths,” author Christy Sutherland, MD, medical director at the PHS Community Services Society, Vancouver, which operates the SAFER program, told this news organization.

PHS Community Services Society

Safe supply programs

Between January 2016 and June 2021, more than 24,000 people died from opioid toxicity in Canada, according to the authors. A key driver of the ongoing public health crisis has been the introduction of illicit fentanyl and other dangerous substances into the unregulated drug supply.

In recent years, several harm-reduction options and substance use disorder treatment programs have been introduced in Canada to stem overdose deaths. However, they haven’t been sufficient, and the number of deaths continues to rise.

“In 2010, methadone worked, but now even high doses don’t keep people out of withdrawal due to the infiltration of fentanyl,” Dr. Sutherland said. “It’s clinically not working anymore. People are now going through benzodiazepine withdrawal and opiate withdrawal at the same time.”

The changes have led doctors to call for programs that provide legal and regulated sources of psychoactive substances, also known as “safe supply” programs. In particular, low-barrier and flexible options are necessary to meet the needs of various people in the community.

In Vancouver, the SAFER program provides medications that are prescribed off-label as substitutes to the illicit drug supply. A multidisciplinary team oversees the program, including doctors, nurses, pharmacists, social workers, and people who have experience living with substance use.

The program’s approach is akin to the use of medications as treatments for substance use disorder, such as opioid-agonist therapy. However, instead of promoting abstinence, the goal of SAFER is to prevent overdose deaths and other consequences by decreasing reliance on the unregulated drug market.

Enrolled participants can access medications, including opioids such as hydromorphone and fentanyl, as a substitute for the unregulated substances that they consume. A notable aspect of SAFER is the offer of fentanyl – with a known potency and without dangerous adulterants found in the local drug supply.
 

Promoting participant autonomy

Given the increasing rate of overdose deaths involving stimulants in Canada, the program also offers prescribed psychostimulants, such as methylphenidate and dextroamphetamine.

The program focuses on harm reduction and promoting participant autonomy. SAFER doesn’t have a predetermined schedule for medication access, which allows participants to return as they need.

“Creating this program has required patience to change our practices,” Dr. Sutherland said. “As you learn more and do more, you’re always growing because you care about your patients and want to help them, especially vulnerable people with a high risk for death.”

The SAFER program is integrated into health care and social services, and participants have access to on-site primary care from clinicians trained in addiction medicine. The program is located alongside a low-barrier prevention site, where supplies such as syringes, take-home naloxone kits, and drug-checking services are available.

The SAFER program will undergo a scientific evaluation, led by two of the co-authors, which will include about 200 participants. During a 2-year period, the evaluation will assess whether the program reduces the risk for overdose deaths and supports access to primary care, harm reduction, and substance use disorder treatment. In addition, the researchers will analyze other key outcomes, such as fatal versus nonfatal overdoses, medication adherence, and the qualitative lived experience of participants.
 

The end of prohibition?

“We’ve had the same challenges with people buying illegal drugs on the street for almost 30 years, but about 5 years ago, that all changed when fentanyl became a prominent drug, and overdose deaths skyrocketed,” Mark Tyndall, MD, a public health professor at the University of British Columbia, Vancouver, said in an interview.

University of British Columbia

Dr. Tyndall is also executive director of the British Columbia Centre for Disease Control and executive director of MySafe Society, a safe supply program in Canada for those with opioid addiction. He is not involved in the SAFER program.

SAFER and MySafe Society are positioned as low-barrier programs, he said, meaning that the public health response is primarily focused on preventing deaths and helping people to get access to medication that won’t kill them. The idea is to meet people where they are today.

However, these programs still face major barriers, such as limitations from federal regulators and stigmas around illicit drugs and harm-reduction programs.

“These beliefs are entrenched, and it takes a long time to help people understand that prohibition means that dangerous drugs are on the street,” he said. “I don’t think way more people are using than 10 years ago, but there was a supply of heroin that was stable in potency back then, and people weren’t dying.”

Ultimately, Dr. Tyndall said, drug policy experts would like to create a regulated supply, similar to the supply of cannabis. The political and regulatory process may take much longer to catch up, but he believes that it’s the most ethical way to reduce overdose deaths and the unregulated drug supply.

“The harshest critics of harm reduction often go to the liquor store every weekend,” he said. “It’s going to be a long process before people think this way, but having fentanyl and other dangerous drugs on the street has signaled the end stage of prohibition.”

The SAFER program is operated by PHS Community Services Society in partnership with Vancouver Coastal Health and funded through Health Canada’s Substance Use and Addiction Program. Dr. Tyndall reported no relevant disclosures.

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

The Safer Alternatives for Emergency Response (SAFER) program provides a safe supply of substances to prevent drug overdose deaths, according to a new report.

The program has been operating in Vancouver, British Columbia, since April 2021. So far, the program has enrolled 58 participants who have reported benefits from having new options when other forms of treatment or harm reduction didn’t work. In addition, doctors who work with the program have reported increased medication adherence among the participants, as well as better chronic disease management.

Similar safe supply programs are being implemented or considered in other places across Canada. Since 2019, Health Canada has funded 18 safe supply pilot programs.

“When we look at the number of overdose deaths, it should be zero. These are preventable deaths,” author Christy Sutherland, MD, medical director at the PHS Community Services Society, Vancouver, which operates the SAFER program, told this news organization.

PHS Community Services Society

Safe supply programs

Between January 2016 and June 2021, more than 24,000 people died from opioid toxicity in Canada, according to the authors. A key driver of the ongoing public health crisis has been the introduction of illicit fentanyl and other dangerous substances into the unregulated drug supply.

In recent years, several harm-reduction options and substance use disorder treatment programs have been introduced in Canada to stem overdose deaths. However, they haven’t been sufficient, and the number of deaths continues to rise.

“In 2010, methadone worked, but now even high doses don’t keep people out of withdrawal due to the infiltration of fentanyl,” Dr. Sutherland said. “It’s clinically not working anymore. People are now going through benzodiazepine withdrawal and opiate withdrawal at the same time.”

The changes have led doctors to call for programs that provide legal and regulated sources of psychoactive substances, also known as “safe supply” programs. In particular, low-barrier and flexible options are necessary to meet the needs of various people in the community.

In Vancouver, the SAFER program provides medications that are prescribed off-label as substitutes to the illicit drug supply. A multidisciplinary team oversees the program, including doctors, nurses, pharmacists, social workers, and people who have experience living with substance use.

The program’s approach is akin to the use of medications as treatments for substance use disorder, such as opioid-agonist therapy. However, instead of promoting abstinence, the goal of SAFER is to prevent overdose deaths and other consequences by decreasing reliance on the unregulated drug market.

Enrolled participants can access medications, including opioids such as hydromorphone and fentanyl, as a substitute for the unregulated substances that they consume. A notable aspect of SAFER is the offer of fentanyl – with a known potency and without dangerous adulterants found in the local drug supply.
 

Promoting participant autonomy

Given the increasing rate of overdose deaths involving stimulants in Canada, the program also offers prescribed psychostimulants, such as methylphenidate and dextroamphetamine.

The program focuses on harm reduction and promoting participant autonomy. SAFER doesn’t have a predetermined schedule for medication access, which allows participants to return as they need.

“Creating this program has required patience to change our practices,” Dr. Sutherland said. “As you learn more and do more, you’re always growing because you care about your patients and want to help them, especially vulnerable people with a high risk for death.”

The SAFER program is integrated into health care and social services, and participants have access to on-site primary care from clinicians trained in addiction medicine. The program is located alongside a low-barrier prevention site, where supplies such as syringes, take-home naloxone kits, and drug-checking services are available.

The SAFER program will undergo a scientific evaluation, led by two of the co-authors, which will include about 200 participants. During a 2-year period, the evaluation will assess whether the program reduces the risk for overdose deaths and supports access to primary care, harm reduction, and substance use disorder treatment. In addition, the researchers will analyze other key outcomes, such as fatal versus nonfatal overdoses, medication adherence, and the qualitative lived experience of participants.
 

The end of prohibition?

“We’ve had the same challenges with people buying illegal drugs on the street for almost 30 years, but about 5 years ago, that all changed when fentanyl became a prominent drug, and overdose deaths skyrocketed,” Mark Tyndall, MD, a public health professor at the University of British Columbia, Vancouver, said in an interview.

University of British Columbia

Dr. Tyndall is also executive director of the British Columbia Centre for Disease Control and executive director of MySafe Society, a safe supply program in Canada for those with opioid addiction. He is not involved in the SAFER program.

SAFER and MySafe Society are positioned as low-barrier programs, he said, meaning that the public health response is primarily focused on preventing deaths and helping people to get access to medication that won’t kill them. The idea is to meet people where they are today.

However, these programs still face major barriers, such as limitations from federal regulators and stigmas around illicit drugs and harm-reduction programs.

“These beliefs are entrenched, and it takes a long time to help people understand that prohibition means that dangerous drugs are on the street,” he said. “I don’t think way more people are using than 10 years ago, but there was a supply of heroin that was stable in potency back then, and people weren’t dying.”

Ultimately, Dr. Tyndall said, drug policy experts would like to create a regulated supply, similar to the supply of cannabis. The political and regulatory process may take much longer to catch up, but he believes that it’s the most ethical way to reduce overdose deaths and the unregulated drug supply.

“The harshest critics of harm reduction often go to the liquor store every weekend,” he said. “It’s going to be a long process before people think this way, but having fentanyl and other dangerous drugs on the street has signaled the end stage of prohibition.”

The SAFER program is operated by PHS Community Services Society in partnership with Vancouver Coastal Health and funded through Health Canada’s Substance Use and Addiction Program. Dr. Tyndall reported no relevant disclosures.

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

The Safer Alternatives for Emergency Response (SAFER) program provides a safe supply of substances to prevent drug overdose deaths, according to a new report.

The program has been operating in Vancouver, British Columbia, since April 2021. So far, the program has enrolled 58 participants who have reported benefits from having new options when other forms of treatment or harm reduction didn’t work. In addition, doctors who work with the program have reported increased medication adherence among the participants, as well as better chronic disease management.

Similar safe supply programs are being implemented or considered in other places across Canada. Since 2019, Health Canada has funded 18 safe supply pilot programs.

“When we look at the number of overdose deaths, it should be zero. These are preventable deaths,” author Christy Sutherland, MD, medical director at the PHS Community Services Society, Vancouver, which operates the SAFER program, told this news organization.

PHS Community Services Society

Safe supply programs

Between January 2016 and June 2021, more than 24,000 people died from opioid toxicity in Canada, according to the authors. A key driver of the ongoing public health crisis has been the introduction of illicit fentanyl and other dangerous substances into the unregulated drug supply.

In recent years, several harm-reduction options and substance use disorder treatment programs have been introduced in Canada to stem overdose deaths. However, they haven’t been sufficient, and the number of deaths continues to rise.

“In 2010, methadone worked, but now even high doses don’t keep people out of withdrawal due to the infiltration of fentanyl,” Dr. Sutherland said. “It’s clinically not working anymore. People are now going through benzodiazepine withdrawal and opiate withdrawal at the same time.”

The changes have led doctors to call for programs that provide legal and regulated sources of psychoactive substances, also known as “safe supply” programs. In particular, low-barrier and flexible options are necessary to meet the needs of various people in the community.

In Vancouver, the SAFER program provides medications that are prescribed off-label as substitutes to the illicit drug supply. A multidisciplinary team oversees the program, including doctors, nurses, pharmacists, social workers, and people who have experience living with substance use.

The program’s approach is akin to the use of medications as treatments for substance use disorder, such as opioid-agonist therapy. However, instead of promoting abstinence, the goal of SAFER is to prevent overdose deaths and other consequences by decreasing reliance on the unregulated drug market.

Enrolled participants can access medications, including opioids such as hydromorphone and fentanyl, as a substitute for the unregulated substances that they consume. A notable aspect of SAFER is the offer of fentanyl – with a known potency and without dangerous adulterants found in the local drug supply.
 

Promoting participant autonomy

Given the increasing rate of overdose deaths involving stimulants in Canada, the program also offers prescribed psychostimulants, such as methylphenidate and dextroamphetamine.

The program focuses on harm reduction and promoting participant autonomy. SAFER doesn’t have a predetermined schedule for medication access, which allows participants to return as they need.

“Creating this program has required patience to change our practices,” Dr. Sutherland said. “As you learn more and do more, you’re always growing because you care about your patients and want to help them, especially vulnerable people with a high risk for death.”

The SAFER program is integrated into health care and social services, and participants have access to on-site primary care from clinicians trained in addiction medicine. The program is located alongside a low-barrier prevention site, where supplies such as syringes, take-home naloxone kits, and drug-checking services are available.

The SAFER program will undergo a scientific evaluation, led by two of the co-authors, which will include about 200 participants. During a 2-year period, the evaluation will assess whether the program reduces the risk for overdose deaths and supports access to primary care, harm reduction, and substance use disorder treatment. In addition, the researchers will analyze other key outcomes, such as fatal versus nonfatal overdoses, medication adherence, and the qualitative lived experience of participants.
 

The end of prohibition?

“We’ve had the same challenges with people buying illegal drugs on the street for almost 30 years, but about 5 years ago, that all changed when fentanyl became a prominent drug, and overdose deaths skyrocketed,” Mark Tyndall, MD, a public health professor at the University of British Columbia, Vancouver, said in an interview.

University of British Columbia

Dr. Tyndall is also executive director of the British Columbia Centre for Disease Control and executive director of MySafe Society, a safe supply program in Canada for those with opioid addiction. He is not involved in the SAFER program.

SAFER and MySafe Society are positioned as low-barrier programs, he said, meaning that the public health response is primarily focused on preventing deaths and helping people to get access to medication that won’t kill them. The idea is to meet people where they are today.

However, these programs still face major barriers, such as limitations from federal regulators and stigmas around illicit drugs and harm-reduction programs.

“These beliefs are entrenched, and it takes a long time to help people understand that prohibition means that dangerous drugs are on the street,” he said. “I don’t think way more people are using than 10 years ago, but there was a supply of heroin that was stable in potency back then, and people weren’t dying.”

Ultimately, Dr. Tyndall said, drug policy experts would like to create a regulated supply, similar to the supply of cannabis. The political and regulatory process may take much longer to catch up, but he believes that it’s the most ethical way to reduce overdose deaths and the unregulated drug supply.

“The harshest critics of harm reduction often go to the liquor store every weekend,” he said. “It’s going to be a long process before people think this way, but having fentanyl and other dangerous drugs on the street has signaled the end stage of prohibition.”

The SAFER program is operated by PHS Community Services Society in partnership with Vancouver Coastal Health and funded through Health Canada’s Substance Use and Addiction Program. Dr. Tyndall reported no relevant disclosures.

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