Evaluating the substance use disorder treatment gap in the United States, 2016-2019: A population health observational study.

BACKGROUND AND OBJECTIVES: Only 10% of Americans with substance use disorders (SUDs) receive treatment with insufficient treatment access and screening practices proposed and potential contributing factors. METHODS: This retrospective cross-sectional study used National Survey on Drug Use and Health (NSDUH) data to assess individuals with SUDs receiving treatment between 2016 and 2019 (survey n = 12,111; weighted n = 12,394,214). Demographic, access, and screening characteristics were investigated as predictors of treatment receipt using time-series logistic regression analyses to test trends and assessed treatment receipt odds, controlling for demographic and treatment characteristics. RESULTS: For those with past-year SUDs, 13.0% reported receiving past-year SUD treatment (survey n = 1605; weighted n = 1,612,154). The SUD treatment receipt rate remained statistically stable from 2016 to 2019, with a nonsignificant treatment receipt trend declining from 14% to 12%. Treatment changes were notable among Native Americans (+53.80%), Pacific Islanders (+94.10%), multiracial (-59.96%), ages 65+ (-70.18%), and ages 12-17 (-50.70%). In the regression model, race, sex, age, insurance status, and receiving mental health treatment were associated with SUD treatment receipt. DISCUSSION AND CONCLUSIONS: The treatment gap remains substantial and stable. Annually, about 87% of Americans with SUDs are not receiving the treatment they need. Asian Americans were less likely and those attending general mental health services were more likely to receive treatment. SCIENTIFIC SIGNIFICANCE: We present an updated SUD treatment gap evaluation, and identify access and screening characteristics associated with SUD treatment receipt. Policymakers, clinicians, and researchers must continue improving access and identification of those in need of care.

Three types of university students with subthreshold depression characterized by distinctive cognitive behavioral skills.

Subthreshold depression impairs young people's quality of life and places them at greater risk of developing major depression. Cognitive behavioral therapy (CBT) is an evidence-based approach for addressing such depressive states. This study identified subtypes of university students with subthreshold depression and revealed discrete profiles of five CBT skills: self-monitoring, cognitive restructuring, behavioral activation, assertive communication, and problem solving. Using data from the Healthy Campus Trial (registration number: UMINCTR-000031307), a hierarchical clustering analysis categorized 1,080 students into three clusters: Reflective Low-skilled, Non-reflective High-skilled, and Non-reflective Low-skilled students. Non-reflective Low-skilled students were significantly more depressed than other students (p < .001). The severity of depression seemed to be related to the combination of self-monitoring skills and other CBT skills. Considering the high prevalence of poor self-monitoring skills in persons with autism, the most severe depression was observed in the significant association between Non-reflective Low-skilled students and autistic traits (p = .008). These findings suggest that subthreshold depression can be categorized into three subtypes based on CBT skill profiles. The assessment of autistic traits is also suggested when we provide CBT interventions for Non-reflective Low-skilled students.

The Impact of the COVID-19 Pandemic and Associated Control Measures on the Mental Health of the General Population : A Systematic Review and Dose-Response Meta-analysis.

BACKGROUND: To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. PURPOSE: To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose-response relations with characteristics of the pandemic and its containment. DATA SOURCES: Relevant articles were identified from the living evidence database of the COVID-19 Open Access Project, which indexes COVID-19-related publications from MEDLINE via PubMed, Embase via Ovid, and PsycInfo. Preprint publications were not considered. STUDY SELECTION: Longitudinal studies that reported data on the general population's mental health using validated scales and that were published before 31 March 2021 were eligible. DATA EXTRACTION: An international crowd of 109 trained reviewers screened references and extracted study characteristics, participant characteristics, and symptom scores at each timepoint. Data were also included for the following country-specific variables: days since the first case of SARS-CoV-2 infection, the stringency of governmental containment measures, and the cumulative numbers of cases and deaths. DATA SYNTHESIS: In a total of 43 studies (331 628 participants), changes in symptoms of psychological distress, sleep disturbances, and mental well-being varied substantially across studies. On average, depression and anxiety symptoms worsened in the first 2 months of the pandemic (standardized mean difference at 60 days, -0.39 [95% credible interval, -0.76 to -0.03]); thereafter, the trajectories were heterogeneous. There was a linear association of worsening depression and anxiety with increasing numbers of reported cases of SARS-CoV-2 infection and increasing stringency in governmental measures. Gender, age, country, deprivation, inequalities, risk of bias, and study design did not modify these associations. LIMITATIONS: The certainty of the evidence was low because of the high risk of bias in included studies and the large amount of heterogeneity. Stringency measures and surges in cases were strongly correlated and changed over time. The observed associations should not be interpreted as causal relationships. CONCLUSION: Although an initial increase in average symptoms of depression and anxiety and an association between higher numbers of reported cases and more stringent measures were found, changes in mental health symptoms varied substantially across studies after the first 2 months of the pandemic. This suggests that different populations responded differently to the psychological stress generated by the pandemic and its containment measures. PRIMARY FUNDING SOURCE: Swiss National Science Foundation. (PROSPERO: CRD42020180049).

Prevalence of gambling disorder and its correlates among homeless men in Osaka city, Japan.

Internationally, the prevalence of gambling disorder has been reported to be higher among homeless people than the general population; however, little is known about the factors associated with gambling disorder in this population. The present study aimed to investigate the prevalence of gambling disorder and its associated factors among homeless men using shelters in Osaka City. A cross-sectional survey was conducted from 30 to 2018 to 4 January 2019, using the 2017 Japanese National Survey of Gambling (JNSG) questionnaire, supplemented with questions about homeless experiences, drinking, and smoking. Using the South Oaks Gambling Screen, the presence of gambling disorder was determined by a score ≥ 5 out of 20. Multivariate logistic regression was conducted to explore factors associated with lifetime gambling disorder. Lifetime and past-year prevalence of gambling disorder among 103 participants was 43.7% (95% confidence interval [CI]: 34.5-53.3) and 3.9% (95% CI: 1.5-9.6), respectively, which are higher than the 6.7% and 1.5% found among men in the 2017 JNSG. Reasons reported for currently gambling less were primarily financial. Factors associated with lifetime GD included "more than 20 years since the first incidence of homelessness" (adjusted odds ratio [AOR]: 4.97, 95% CI: 1.50-16.45) and "more than five incidences of homelessness" (AOR: 4.51, 95% CI: 1.06-19.26). When homeless individuals with gambling disorder try to rebuild and stabilize their lives, the presence or resurgence of gambling disorder may hinder the process and pose a risk of recurring homelessness. Comprehensive support services for homeless individuals with gambling disorder are required. (250 words).

Group Cognitive-Behavioral Therapy With Interoceptive Exposure for Drug-Refractory Irritable Bowel Syndrome: A Randomized Controlled Trial.

INTRODUCTION: Few people can access psychotherapy for irritable bowel syndrome (IBS). Group cognitive-behavioral therapy (GCBT) may be efficient, but the evidence for its efficacy is weak and limited. We aimed to assess the efficacy and safety of GCBT with interoceptive exposure (GCBT-IE), a novel form of GCBT for drug-refractory IBS. METHODS: A single-center, open-label, randomized, controlled trial was conducted in Japan among people aged 18-75 years with moderate-to-severe drug-refractory IBS. Participants were stratified by IBS severity and allocated 1:1 to 10-week GCBT-IE or waiting list (WL) in a blockwise randomization by independent staff. Both arms practiced self-monitoring and received treatment as usual. Multiple primary outcomes were changes from baseline to week 13 in the IBS Symptom Severity Score and the IBS Quality of Life Measure (IBS-QOL), assessed in the intention-to-treat sample. RESULTS: A total of 114 people with drug-refractory IBS were randomized to GCBT-IE (n = 54) or WL (n = 60). Forty-nine participants (90.7%) in the GCBT-IE arm and 58 (96.7%) in the WL arm completed the week 13 assessment. Participants in the GCBT-IE arm reported greater improvements in both IBS symptom severity and quality of life compared with the WL arm, with -115.8 vs -29.7 on the IBS Symptom Severity Score (a difference of -86.1, 95% confidence interval -117.3 to -55.0), and 20.1 vs -0.2 on the IBS-QOL (a difference of 20.3, 95% confidence interval 15.2-25.3), respectively. Six unexpected serious adverse events were reported but were judged as unrelated to the interventions. DISCUSSION: GCBT-IE is an efficacious, safe, and efficient treatment option for people with drug-refractory IBS.

Efficacy of Brief Intervention for Unhealthy Drug Use in Outpatient Medical Care: a Systematic Review and Meta-analysis.

BACKGROUND: The efficacy of brief intervention (BI) for unhealthy drug use in outpatient medical care has not been sufficiently substantiated through meta-analysis despite its ongoing global delivery. This study aims to determine the efficacy of BI for unhealthy drug use and the expected length of effects, and describe subgroup analyses by outpatient setting. METHODS: Trials comparing BI with usual care controls were retrieved through four databases up to January 13, 2021. Two reviewers independently screened, selected, and extracted data. Primary outcomes included drug use frequency (days used) and severity on validated scales at 4-8 months and were analyzed using random-effects model meta-analysis. RESULTS: In total, 20 studies with 9182 randomized patients were included. There was insufficient evidence to support the efficacy of BI for unhealthy drug use among all outpatient medical care settings for use frequency (SMD = -0.07, 95% CI = -0.17, 0.02, p = 0.12, I2 = 37%, high certainty of evidence) and severity (SMD = -0.27, 95% CI = -0.78, 0.24, p = 0.30, I2 = 98%, low certainty of evidence). However, post hoc subgroup analyses uncovered significant effects for use frequency by setting (interaction p = 0.02), with significant small effects only in emergency departments (SMD = -0.15, 95% CI = -0.25, -0.04, p < 0.01). Primary care, student health, women's health, and HIV primary care subgroups were nonsignificant. Primary care BI revealed nonsignificant greater average use in the treatment group compared to usual care. DISCUSSION: BI for unhealthy drug use lacks evidence of efficacy among all outpatient medical settings. However, small effects found in emergency departments may indicate incremental benefits for some patients. Clinical decisions for SBI or specialty treatment program referrals should be carefully considered accounting for these small effects in emergency departments. REGISTRATION: PROSPERO (CRD42020157733).

State population indices predict Asian American and Pacific Islander successful substance use treatment completion: An exploratory observational study.

Cultural capital is a known factor supporting success in substance use disorder (SUD) treatment. We investigated Asian American and Pacific Islander (AAPI) State population metrics in relation to SUD treatment completion for US clients from 2006-2017 (N = 5,404,374). Metrics that may signify greater available cultural capital were State AAPI Percentage, State AAPI Percent Change, and State AAPI Population. AAPI Percentage, AAPI Percent Change were positively associated, while AAPI Population was negatively associated with treatment completion (p < 0.001). Findings suggest treatment agencies in areas with low AAPI densities may improve outcomes by supporting AAPI community and cultural social networks.

Microaggressions and marijuana use among college students.

This study examines the association between exposure to microaggressions and marijuana use, using original survey data from a sample of racial/ethnic minority college students (n = 332) from a large Division I university in the United States. Nearly all of our sample (96%) reported at least one experience with microaggressions in the past 6 months, while 33% reported using marijuana regularly. We modeled regular use of marijuana using multiple logistic regression, with consideration of sex, age, race/ethnicity, and microaggression scale scores as covariates. Age, sex, the microinvalidations subscale score, and the full microaggression scale score were significantly associated with marijuana use in our full models (p < .01; p = .01; p = .02; p = .03, respectively). With each additional experience of microaggression, the odds of regular marijuana use increase. Academic communities may consider the primary prevention of discriminatory behavior when addressing student substance use.

Trends of Youth Marijuana Treatment Admissions: Increasing Admissions Contrasted with Decreasing Drug Involvement.

BACKGROUND: Recent changes in marijuana policies and their potential negative effects on youth development are a public health concern. Identifying the most appropriate treatment approaches for problematic marijuana use is important. OBJECTIVES: The aim of this study was to track marijuana use among young people by examining national changes from 1995 to 2012 in the demographics, referral sources, and the substance use patterns related to youth admissions to substance abuse treatment programs. METHODS: We examined first-time substance abuse treatment admissions among youth, utilizing the Treatment Episode Data Set - Admissions (TEDS-A) of the Substance Abuse Mental Health Services Administration (N = 12,025,787). Chi-squared analysis was used to examine differences between admission years and binomial logistic regression was used to examine trends over the 18 years. RESULTS: We found increasing numbers of youth in dependent living situations (e.g. with parents) admitted to substance use disorder treatment for marijuana. We also found a dramatic drop in the degree of drug involvement for those admissions over nearly two decades of data. Conclusions/Importance: While availability and changing perceptions of marijuana might have caused an increase in admissions to substance abuse treatment, our findings indicate that the severity of drug use involved in those admissions has decreased. This study highlights the importance of identifying youth in actual need of treatment services and not overlooking tools such as screening, brief intervention, and motivational interviewing as effective for varying levels of marijuana use by youth.

A brief report on Hispanic youth marijuana use: Trends in substance abuse treatment admissions in the United States.

Increases in Hispanic youth admissions to substance abuse treatment programs for marijuana use are a growing public health concern. In this study, we investigated trends in Hispanic youth from 1995 to 2012 utilizing the Treatment Episode Data Set-Admissions of the Substance Abuse Mental Health Services Administration. Hispanic youth marijuana admissions are associated with youth 15-17 years old, in high school, and living in a dependent situation. Notably, female admissions increased at greater rates than males. Results also point to decreasing tolerance of minor marijuana use by schools and community agencies. Findings highlight the need for targeted, culturally specific, and cost-effective treatment and prevention efforts.

Differences in successful treatment completion among pregnant and non-pregnant American women.

The present study explores characteristics of successful substance abuse treatment completion of pregnant women through an analysis of retrospective outcomes data. Women without prior treatment admissions, aged 18-44, and not in methadone maintenance therapy were included (N = 678,782). Chi-square tests analyzed significant differences; logistic regression provided predictive probabilities; odds ratios (OR) and risk differences with 95 % confidence intervals represent the effect sizes and clinically meaningful differences. Pregnant women were less likely to successfully complete treatment than non-pregnant women (χ (2) = 321.33, df = 1, p < 0.0001), though the difference was not clinically meaningful (risk difference = 4.75, 95 % confidence interval (CI) = 4.23-5.26). Aside from criminal justice agencies, "other community agencies" refer the greatest percentage of pregnant women to treatment (risk difference = 6.37, 95 % CI = 5.89-6.84). Pregnant women successfully complete treatment more than non-pregnant women in only non-intensive outpatient settings (χ (2) = 10,182.48, df = 7, p < 0.0001). Further attention to referral source and treatment setting for pregnant women may improve successful treatment completion by targeting needs of pregnant women. Referring to non-intensive outpatient and residential hospital treatment settings may help to ameliorate prenatal substance abuse treatment contingent on the primary problem substance.

Integration of substance use disorder treatment in traditional mental health facilities: Timeseries and cross-sectional evaluations.

BACKGROUND: Despite efforts to increase substance use disorder (SUD) treatment provision in the United States (US), the extent to which traditional mental health (MH) facilities offer SUD treatment remains unclear. In the present study, we analyzed the trend in SUD treatment integration among traditional MH facilities in the US from 2014 to 2020 and identified facility-level factors associated with SUD treatment provision. METHODS: Data were extracted from the National Mental Health Services Survey (N-MHSS). A timeseries logit trend analysis for the multi-year dataset (2014-2020) was conducted to assess a yearly change in odds of SUD treatment provision. With the 2020 survey data, analyses were conducted to identify the differences between facilities offering SUD treatment and facilities not offering such treatment. Finally, exploratory multivariable logistic regression was conducted to estimate odds of SUD treatment provision by facility variables. RESULTS: US MH facility SUD treatment provision went from 51.7 % (2014) to 57.9 % (2020). A mean sample of 12,312 US MH facilities over seven years, demonstrated a significant but small yearly increase in SUD treatment provision (OR = 1.04, 95 % CI = 1.03, 1.04). Important facility characteristics related to SUD treatment provision for facilities without a core SUD focus were MH diagnostics offered (OR = 2.03), dual-diagnosis program offered (OR = 3.65), state drug/alcohol license maintained (OR = 6.66), and VA setting (OR = 7.94). CONCLUSIONS: Despite incremental progress in integrating SUD treatment services into US MH facilities, the SUD treatment gap remains large. Training and service development incentives for identified characteristics could help further reduce the treatment gap.

The short and long-term efficacy of nurse-led interventions for improving blood pressure control in people with hypertension in primary care settings: a systematic review and meta-analysis.

BACKGROUND: Previous systematic reviews suggest that nurse-led interventions improve short-term blood pressure (BP) control for people with hypertension. However, the long-term effects, adverse events, and appropriate target BP level are unclear. This study aimed to evaluate the long-term efficacy and safety of nurse-led interventions. METHODS: We conducted a systematic review and meta-analysis. We searched the Cochrane Central Register of Controlled Trials, PubMed, and CINAHL, as well as three Japanese article databases, as relevant randomized controlled trials from the oldest possible to March 2021. This search was conducted on 17 April 2021. We did an update search on 17 October 2023. We included studies on adults aged 18 years or older with hypertension. The treatments of interest were community-based nurse-led BP control interventions in addition to primary physician-provided care as usual. The comparator was usual care only. Primary outcomes were long-term achievement of BP control goals and serious adverse events (range: 27 weeks to 3 years). Secondary outcomes were short-term achievement of BP control goals and serious adverse events (range: 4 to 26 weeks), change of systolic and diastolic BP from baseline, medication adherence, incidence of hypertensive complications, and total mortality. RESULTS: We included 35 studies. Nurse-led interventions improved long-term BP control (RR 1.10, 95%CI 1.03 to 1.18). However, no significant differences were found in the short-term effects of nurse-led intervention compared to usual care about BP targets. Little information on serious adverse events was available. There was no difference in mortality at both terms between the two groups. Establishing the appropriate target BP from the extant trials was impossible. CONCLUSIONS: Nurse-led interventions may be more effective than usual care for achieving BP control at long-term follow-up. It is important to continue lifestyle modification for people with hypertension. We must pay attention to adverse events, and more studies examining appropriate BP targets are needed. Nurse-led care represents an important complement to primary physician-led usual care.

Estimating the smallest worthwhile difference of antidepressants: a cross-sectional survey.

BACKGROUND: Approximately 30% of patients experience substantial improvement in depression after 2 months without treatment, and 45% with antidepressants. The smallest worthwhile difference (SWD) refers to an intervention's smallest beneficial effect over a comparison patients deem worthwhile given treatment burdens (harms, expenses and inconveniences), but is undetermined for antidepressants. OBJECTIVE: Estimating the SWD of commonly prescribed antidepressants for depression compared to no treatment. METHODS: The SWD was estimated as a patient-required difference in response rates between antidepressants and no treatment after 2 months. An online cross-sectional survey using Prolific, MQ Mental Health and Amazon Mechanical Turk crowdsourcing services in the UK and USA between October 2022 and January 2023 garnered participants (N=935) that were a mean age of 44.1 (SD=13.9) and 66% women (n=617). FINDINGS: Of 935 participants, 124 reported moderate-to-severe depressive symptoms but were not in treatment, 390 were in treatment and 495 reported absent-to-mild symptoms with or without treatment experiences. The median SWD was a 20% (IQR=10-30%) difference in response rates for people with moderate-to-severe depressive symptoms, not in treatment, and willing to consider antidepressants, and 25% (IQR=10-35%) for the full sample. CONCLUSIONS: Our observed SWDs mean that the current 15% antidepressant benefit over no treatment was sufficient for one in three people to accept antidepressants given the burdens, but two in three expected greater treatment benefits. IMPLICATIONS: While a minority may be satisfied with the best currently available antidepressants, more effective and/or less burdensome medications are needed, with more attention given to patient perspectives.

A Review of Parental Vaccine Hesitancy for Human Papillomavirus in Japan.

Globally, Japan has the lowest rate of vaccine confidence. The persistent parental vaccine hesitancy has been attributed to safety and efficacy concerns and is primarily driven by the negative experience with human papillomavirus (HPV) vaccines. This literature review aimed to identify factors associated with HPV vaccine uptake and potential strategies to reduce vaccine hesitancy among Japanese parents. Articles published in English or Japanese between January 1998 and October 2022 that examined Japanese parental factors for HPV vaccine uptake were identified from PubMed, Web of Science, and Ichushi-Web. In total, 17 articles met the inclusion criteria. Four key themes which affected HPV vaccine hesitancy and acceptance were identified: perceptions of risk and benefits, trust and recommendation, information and knowledge, and sociodemographic characteristics. While governmental and healthcare provider recommendations are important factors, efforts to improve parental confidence in the HPV vaccine are required. Future interventions to counteract HPV vaccine hesitancy should actively disseminate information on vaccine safety and effectiveness, along with information on the severity and susceptibility of HPV infection.

Proportion attributable to contextual effects in general medicine: a meta-epidemiological study based on Cochrane reviews.

OBJECTIVES: Our objectives were to examine the magnitude of the proportion attributable to contextual effects (PCE), which shows what proportion of the treatment arm response can be achieved by the placebo arm across various interventions, and to examine PCE variability by outcome type and condition. DESIGN: We conducted a meta-epidemiological study. SETTING: We searched the Cochrane Database of Systematic Reviews with the keyword 'placebo' in titles, abstracts and keywords on 1 January 2020. PARTICIPANTS: We included reviews that showed statistically significant beneficial effects of the intervention over placebo for the first primary outcome. MAIN OUTCOME MEASURES: We performed a random-effects meta-analysis to calculate PCEs based on the pooled result of each included review, grouped by outcome type and condition. The PCE quantifies how much of the observed treatment response can be achieved by the contextual effects. PUBLIC AND PATIENT INVOLVEMENT STATEMENT: No patient or member of the public was involved in conducting this research. RESULTS: We included 328 out of 3175 Cochrane systematic reviews. The results of meta-analyses showed that PCEs varied greatly depending on outcome type (I2=98%) or condition (I2=98%), but mostly lie between 0.40 and 0.95. Overall, the PCEs were 0.65 (95% CI 0.59 to 0.72) on average. Subjective outcomes were 0.50 (95% CI 0.41 to 0.59), which was significantly smaller than those of semiobjective (PCE 0.78; 95% CI 0.72 to 0.85) or objective outcomes (PCE 0.94; 95% CI 0.91 to 0.97). CONCLUSIONS: The results suggest that much of the observed benefit is not just due to the specific effect of the interventions. The specific effects of interventions may be larger for subjective outcomes than for objective or semiobjective outcomes. However, PCEs were exceptionally variable. When we evaluate the magnitude of PCEs, we should consider each PCE individually, for each condition, intervention and outcome in its context, to assess the importance of an intervention for each specific clinical setting.

Efficacy of Integrated Online Mindfulness and Self-compassion Training for Adults With Atopic Dermatitis: A Randomized Clinical Trial.

Importance: Quality of life (QOL) of patients with atopic dermatitis (AD) is reported to be the lowest among skin diseases. To our knowledge, mindfulness and self-compassion training has not been evaluated for adults with AD. Objective: To evaluate the efficacy of mindfulness and self-compassion training in improving the QOL for adults with AD. Design, Setting, and Participants: This randomized clinical trial conducted from March 2019 through October 2022 included adults with AD whose Dermatology Life Quality Index (DLQI) score, a skin disease-specific QOL measure, was greater than 6 (corresponding to moderate or greater impairment). Participants were recruited from multiple outpatient institutes in Japan and through the study's social media outlets and website. Interventions: Participants were randomized 1:1 to receive eight 90-minute weekly group sessions of online mindfulness and self-compassion training or to a waiting list. Both groups were allowed to receive any dermatologic treatment except dupilumab. Main Outcomes and Measures: The primary outcome was the change in the DLQI score from baseline to week 13. Secondary outcomes included eczema severity, itch- and scratching-related visual analog scales, self-compassion and all of its subscales, mindfulness, psychological symptoms, and participants' adherence to dermatologist-advised treatments. Results: The study randomized 107 adults to the intervention group (n = 56) or the waiting list (n = 51). The overall participant mean (SD) age was 36.3 (10.5) years, 85 (79.4%) were women, and the mean (SD) AD duration was 26.6 (11.7) years. Among participants from the intervention group, 55 (98.2%) attended 6 or more of the 8 sessions, and 105 of all participants (98.1%) completed the assessment at 13 weeks. The intervention group demonstrated greater improvement in the DLQI score at 13 weeks (between-group difference estimate, -6.34; 95% CI, -8.27 to -4.41; P < .001). The standardized effect size (Cohen d) at 13 weeks was -1.06 (95% CI, -1.39 to -0.74). All secondary outcomes showed greater improvements in the intervention group than in the waiting list group. Conclusions and Relevance: In this randomized clinical trial of adults with AD, integrated online mindfulness and self-compassion training in addition to usual care resulted in greater improvement in skin disease-specific QOL and other patient-reported outcomes, including eczema severity. These findings suggest that mindfulness and self-compassion training is an effective treatment option for adults with AD. Trial Registration: https://umin.ac.jp/ctr Identifier: UMIN000036277.

Prognostic factors and effect modifiers for personalisation of internet-based cognitive behavioural therapy among university students with subthreshold depression: A secondary analysis of a factorial trial.

BACKGROUND: Internet-cognitive behavioural therapy (iCBT) for depression can include multiple components. This study explored depressive symptom improvement prognostic factors (PFs) and effect modifiers (EMs) for five common iCBT components including behavioural activation, cognitive restructuring, problem solving, self-monitoring, and assertion training. METHODS: We used data from a factorial trial of iCBT for subthreshold depression among Japanese university students (N = 1093). The primary outcome was the change in PHQ-9 scores at 8 weeks from baseline. Interactions between each component and various baseline characteristics were estimated using a mixed-effects model for repeated measures. We calculated multiplicity-adjusted p-values at 5 % false discovery rate using the Benjamini-Hochberg procedure. RESULTS: After multiplicity adjustment, the baseline PHQ-9 total score emerged as a PF and exercise habits as an EM for self-monitoring (adjusted p-values <0.05). The higher the PHQ-9 total score at baseline (range: 5-14), the greater the decrease after 8 weeks. For each 5-point increase at baseline, the change from baseline to 8 weeks was bigger by 2.8 points. The more frequent the exercise habits (range: 0-2 points), the less effective the self-monitoring component. The difference in PHQ-9 change scores between presence or absence of self-monitoring was smaller by 0.94 points when the participant exercised one level more frequently. Additionally, the study suggested seven out of 36 PFs and 14 out of 160 EMs examined were candidates for future research. LIMITATIONS: Generalizability is limited to university students with subthreshold depression. CONCLUSIONS: These results provide some helpful information for the future development of individualized iCBT algorithms for depression.

US Food and Drug Administration Accelerated Approval Program for Nononcology Drug Indications Between 1992 and 2018.

Importance: The US Food and Drug Administration (FDA) grants accelerated approval according to surrogate measures of numerous drug indications for serious or life-threatening illnesses such as infectious diseases and cancer. Investigators, including the FDA, have evaluated the program's regulatory and clinical consequences in oncology, but evaluation of nononcology drugs is lacking. Objective: To evaluate the accelerated approval program for nononcology drug indications over a period of 26 years. Design, Setting, and Participants: This retrospective cohort study used publicly available data on FDA nononcology drug indications granted accelerated approval from June 1992 through May 2018, with preapproval and confirmatory trials for approved drugs. Data were analyzed from February to April 2022. Main Outcomes and Measures: The study estimated the median time from accelerated approval to occurrence of regulatory outcomes such as regular approval conversion, postapproval boxed warning label changes, confirmatory trial completion, and confirmatory trial results publication. Results: The FDA granted accelerated approval of 48 drugs for 57 nononcology indications, including 23 (40%) HIV treatments, supported by 93 preapproval trials. Forty-three indications (75%) were converted to regular approval at a median time of 53.1 (95% CI, 38.7 to 70.2) months from accelerated approval. There were postapproval label modifications on boxed warnings in 27 indications (47%) with a median time of 248.6 (95% CI, 51.8 to not estimable) months from accelerated approval. Of the 86 required confirmatory trials, 17 (20%) had not fulfilled the postapproval requirements. The median time to confirmatory trial completion was 39.4 (95% CI, 30.7 to 47.9) months. Nine trials (10%) failed to verify clinical efficacy, but only 1 of 8 indications assessed (2%) was withdrawn owing to the failed confirmatory trial, which was 136 months after approval. Results were published in 56 completed confirmatory trials (65%), with the median time being 52.5 (95% CI, 35.6 to 82.2) months from accelerated approval to publication. Conclusions and Relevance: Although the program expedited the approval of nononcology drug indications by a median (IQR) of 53.1 (26.8-133.2) months, safety-related label modifications were often added in boxed warnings after approval, and clinical efficacy was sometimes not confirmed. The study findings and long follow-up period suggest that comprehensive evaluation of such drugs may take more than a decade.

Large variation existed in standardized mean difference estimates using different calculation methods in clinical trials.

BACKGROUND AND OBJECTIVES: The standardized mean difference (SMD) can be calculated from different mean differences (MDs) and standard deviations (SDs). This study aims to investigate how clinical trials calculated, reported and interpreted the SMD, and to examine the variation between different SMDs. METHODS: We searched the PubMed for randomized controlled trials of general medicine and psychiatry that estimated SMDs. We explored how the SMD was computed and interpreted. We calculated SMDs based on different MDs and SDs, and the variation in these SMD estimates for each study. RESULTS: We included 161 articles. Various MDs and SDs were used to calculate SMDs, yet 69.0% studies failed to provide sufficient details. Variations in SMD estimates using different MDs and SDs in one study could be substantial (median of the absolute differences was 0.3, interquartile range IQR 0.17 to 0.53). However, 68.3% studies interpreted the SMD based on the same reference, Cohen's rule of thumb. The largest variations were observed in studies with small sample sizes and large reported effects. CONCLUSION: SMDs using different MDs and SDs could vary considerably, but the report was often insufficient and the interpretation was oversimplified. To avoid selective reporting bias and misinterpretation, prespecifying and reporting the method and interpreting the result from multiple perspectives are desirable.