-
Annals of Medicine Dec 2022Psychotropic medications are commonly prescribed among adults with intellectual disability, often in the absence of a psychiatric diagnosis. The aim of this scoping...
BACKGROUND/OBJECTIVE(S)
Psychotropic medications are commonly prescribed among adults with intellectual disability, often in the absence of a psychiatric diagnosis. The aim of this scoping review is to provide an overview of the extent, range, and nature of the available research on medication use and practices and medication management in people with intellectual disability taking psychotropic medications for behaviours that challenge.
MATERIALS AND METHODS
A scoping review of research studies (qualitative, quantitative, and mixed design) and Grey Literature (English) was carried out. Databases included: Ovid MEDLINE, Embase, CINAHL, JBI Evidence Synthesis, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, and Scopus. A three-step search strategy was followed, with results screened by two independent reviewers. Data was extracted independently by two reviewers using a data extraction tool with results mapped and presented using a narrative form supported by tables and diagrams to the research questions.
RESULTS
Following the removal of duplicates, records were screened, full texts assessed, and 49 studies were included. Medication outcomes included reduced repetitive, stereotypic, and/or aggressive behaviours. High dosing/prescribing in the setting of an absent/unclear clinical indication was associated with worsening of symptoms for which psychotropics were prescribed. While psychotropics had a role in managing behaviours that challenge, reducing or discontinuing psychotropics is sometimes warranted. Study designs were frequently pragmatic resulting in small sample sizes and heterogeneous cohorts receiving different doses and combinations of medications. Access to multidisciplinary teams, guidelines, medication reviews, staff training, and enhanced roles for carers in decision-making were warranted to optimize psychotropic use.
CONCLUSIONS
These findings can inform prescribing interventions and highlight the need for timely and comprehensive patient outcome data, especially on long-term use of high doses of psychotropics and what happens when reduce or stop prescribing these doses.KEY MESSAGESPsychotropic medications are frequently prescribed for people with intellectual disabilities, often at high doses and these medications are associated with both positive and negative patient outcomes.Work to rationalize psychotropic use has been reported with interventions aiming to reduce polypharmacy or deprescribe a single psychotropic medicine. These interventions had mixed success and risk of relapse was documented in some studies.Limitations in sample size and heterogenous patient cohorts make it challenging to understand the risks and benefits associated with reducing or stopping psychotropic medicines.Patient, carer, and clinician partnerships are critical to advance medication management.
Topics: Adult; Databases, Factual; Humans; Intellectual Disability; Polypharmacy; Psychotropic Drugs; Systematic Reviews as Topic
PubMed: 36120887
DOI: 10.1080/07853890.2022.2121853 -
Dermatology (Basel, Switzerland) 2023Hidradenitis suppurativa (HS) is a chronic inflammatory disease that disproportionally affects women, as well as Black and biracial individuals. While adalimumab remains...
BACKGROUND
Hidradenitis suppurativa (HS) is a chronic inflammatory disease that disproportionally affects women, as well as Black and biracial individuals. While adalimumab remains the only therapy approved by the Food and Drug Administration for HS, many HS clinical trials for novel and re-tasked therapies are ongoing or upcoming. To optimize treatment equity, reflect the patient population, and facilitate trial participation, it is important to elucidate aspects of clinical trial protocols that may systematically exclude specific patient groups or impose hardships.
OBJECTIVE
The study aimed to systematically review inclusion and exclusion criteria as well as participant demographics in HS clinical trials.
METHODS
A literature search of PubMed, Embase, Cochrane Central, and Web of Science databases was conducted. Peer-reviewed publications of randomized controlled trials that were written in English and had at least 10 participants were included. Title and abstract screening and data extraction were completed by two independent reviewers, with disagreements resolved by a third.
RESULTS
Twenty-three studies totaling 1,496 adult participants met the inclusion criteria. Race and ethnicity were not reported in 473/1,496 (31.6%) and 1,420/1,496 (94.9%) trial participants, respectively. Trial participants were predominantly white (811/1,023, 79.3%) and female (1,057/1,457, 72.5%). The median of each study's average age was 35.7 years (IQR 33.5-38.0), and 17/23 (73.9%) trials excluded pediatric patients. Nearly all participants had Hurley Stage II (499/958, 52.0%) or Hurley Stage III (385/958, 40.2%) disease. Many trials excluded patients who were pregnant (19/23, 82.6%) and breastfeeding (13/23, 56.5%), or who had HS that was "too severe" (8/23, 34.8%) or "too mild" (16/23, 70.0%). Frequently, trial protocols required prolonged washout periods from HS therapies, relatively long duration in the study's placebo arm, and prohibited concurrent analgesic use.
CONCLUSIONS
This systematic review of 23 HS clinical trials totaling 1,496 participants identified substantial hardships imposed by trial participation, high rates of missing race and ethnicity data, and low representation of key patient groups, including those who identify as Black. Future trials with pragmatic study designs, broader inclusion criteria, and study sites in diverse communities may alleviate burdens of trial participation and improve enrollment of diverse patient groups.
Topics: Adult; Humans; Female; Hidradenitis Suppurativa; Clinical Trials as Topic; Adalimumab; Demography; Randomized Controlled Trials as Topic
PubMed: 36108592
DOI: 10.1159/000526069 -
JAMA Pediatrics Nov 2022Adequate sleep duration is necessary for many aspects of child health, development, and well-being, yet sleep durations for children are declining, and effective... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Adequate sleep duration is necessary for many aspects of child health, development, and well-being, yet sleep durations for children are declining, and effective strategies to increase sleep in healthy children remain to be elucidated.
OBJECTIVE
To determine whether nonpharmaceutical interventions to improve sleep duration in healthy children are effective and to identify the key components of these interventions.
DATA SOURCES
CENTRAL, MEDLINE, Embase, PsycINFO, Web of Science Core collection, ClinicalTrials.gov, and WHO trials databases were searched from inception to November 15, 2021.
STUDY SELECTION
Randomized clinical trials of interventions to improve sleep duration in healthy children were independently screened by 2 researchers. A total of 28 478 studies were identified.
DATA EXTRACTION AND SYNTHESIS
Data were processed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) reporting guideline. Random-effects meta-analytic models were used to estimate pooled effect sizes.
MAIN OUTCOMES AND MEASURES
Difference in sleep duration, measured in minutes.
RESULTS
A total of 13 539 child participants from 45 randomized clinical trials were included. Of these, 6897 (50.9%) were in the intervention group and 6642 (49.1%) in the control group, and the mean age ranged from 18 months to 19 years. Pooled results indicate that sleep interventions were associated with 10.5 minutes (95% CI, 5.6-15.4) longer nocturnal sleep duration. There was substantial variation between trials. Sources of variation that were not associated with the study effect size included age group, whether the population was identified as having a sleep problem or being at a socioeconomic disadvantage (eg, coming from a low-income family or area), method of assessment of sleep duration (objective vs subjective), location of intervention delivery (home vs school), whether interventions were delivered in person or used parental involvement, whether behavioral theory was used, environmental change, or had greater or lower intensity. Interventions that included earlier bedtimes were associated with a 47-minute sleep extension (95% CI, 18.9-75.0; 3 trials) compared with remaining studies (7.4 minutes; 95% CI, 2.9-11.8; 42 trials) (P = .006 for group difference). Trials of shorter duration (6 months or less) had larger effects.
CONCLUSIONS AND RELEVANCE
Interventions focused on earlier bedtimes may offer a simple, pragmatic, effective way to meaningfully increase sleep duration that could have important benefits for child health.
Topics: Child; Humans; Infant; Sleep; Parents; Schools; Time Factors
PubMed: 36094530
DOI: 10.1001/jamapediatrics.2022.3172 -
Nutrients Sep 2022The education sector is recognised as an ideal platform to promote good nutrition and decision making around food and eating. Examining adolescents in this setting is... (Meta-Analysis)
Meta-Analysis Review
The Impact of Modifying Food Service Practices in Secondary Schools Providing a Routine Meal Service on Student's Food Behaviours, Health and Dining Experience: A Systematic Review and Meta-Analysis.
The education sector is recognised as an ideal platform to promote good nutrition and decision making around food and eating. Examining adolescents in this setting is important because of the unique features of adolescence compared to younger childhood. This systematic review and meta-analysis examine interventions in secondary schools that provide a routine meal service and the impact on adolescents’ food behaviours, health and dining experience in this setting. The review was guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist and Cochrane Handbook recommendations. Studies published in English searched in four databases and a hand search yielded 42 interventions in 35 studies. Risk of bias was assessed independently by two reviewers. Interventions were classified using the NOURISHING framework, and their impact analysed using meta-analysis, vote-counting synthesis or narrative summary. The meta-analysis showed an improvement in students selecting vegetables (odds ratio (OR): 1.39; 1.12 to 1.23; p = 0.002), fruit serves selected (mean difference (MD): 0.09; 0.09 to 0.09; p < 0.001) and consumed (MD: 0.10; 0.04 to 0.15; p < 0.001), and vegetable serves consumed (MD: 0.06; 0.01 to 0.10; p = 0.024). Vote-counting showed a positive impact for most interventions that measured selection (15 of 25; 41% to 77%; p = 0.002) and consumption (14 of 24; 39% to 76%; p = 0.013) of a meal component. Interventions that integrate improving menu quality, assess palatability, accessibility of healthier options, and student engagement can enhance success. These results should be interpreted with caution as most studies were not methodologically strong and at higher risk of bias. There is a need for higher quality pragmatic trials, strategies to build and measure sustained change, and evaluation of end-user attitudes and perceptions towards intervention components and implementation for greater insight into intervention success and future directions (PROSPERO registration: CRD42020167133).
Topics: Adolescent; Child; Food Services; Health Behavior; Humans; Schools; Students; Vegetables
PubMed: 36079897
DOI: 10.3390/nu14173640 -
The Cochrane Database of Systematic... Sep 2022Child and adolescent overweight and obesity have increased globally and are associated with significant short- and long-term health consequences. (Review)
Review
BACKGROUND
Child and adolescent overweight and obesity have increased globally and are associated with significant short- and long-term health consequences.
OBJECTIVES
To assess the effects of surgery for treating obesity in childhood and adolescence.
SEARCH METHODS
For this update, we searched Cochrane Central Register of Controlled Trials, MEDLINE, Latin American and Caribbean Health Science Information database (LILACS), World Health Organization International Clinical Trials Registry Platform (ICTRP)and ClinicalTrials.gov on 20 August 2021 (date of the last search for all databases). We did not apply language restrictions. We checked references of identified studies and systematic reviews.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) of surgical interventions for treating obesity in children and adolescents (age < 18 years) with a minimum of six months of follow-up. We excluded interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or which included participants with a secondary or syndromic cause of obesity, or who were pregnant.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Two review authors independently extracted data and assessed the risk of bias using the Cochrane Risk of Bias 2.0 tool. Where necessary, we contacted authors for additional information.
MAIN RESULTS
With this update, we did not find any new RCTs. Therefore, this updated review still includes a single RCT (a total of 50 participants, 25 in both the intervention and comparator groups). The intervention focused on laparoscopic adjustable gastric banding surgery, which was compared to a control group receiving a multi-component lifestyle programme. The participating population consisted of Australian adolescents (a higher proportion of girls than boys) aged 14 to 18 years, with a mean age of 16.5 and 16.6 years in the gastric banding and lifestyle groups, respectively. The trial was conducted in a private hospital, receiving funding from the gastric banding manufacturer. For most of the outcomes, we identified a high risk of bias, mainly due to bias due to missing outcome data. Laparoscopic gastric banding surgery may reduce BMI by a mean difference (MD) of -11.40 kg/m (95% CI -13.22 to -9.58) and weight by -31.60 kg (95% CI -36.66 to -26.54) compared to a multi-component lifestyle programme at two years follow-up. The evidence is very uncertain due to serious imprecision and a high risk of bias. Adverse events were reported in 12/25 (48%) participants in the intervention group compared to 11/25 (44%) in the control group. A total of 28% of the adolescents undergoing gastric banding required revisional surgery. The evidence is very uncertain due to serious imprecision and a high risk of bias. At two years of follow-up, laparoscopic gastric banding surgery may increase health-related quality of life in the physical functioning scores by an MD of 16.30 (95% CI 4.90 to 27.70) and change in health scores by an MD of 0.82 (95% CI 0.18 to 1.46) compared to the lifestyle group. The evidence is very uncertain due to serious imprecision and a high risk of bias. No data were reported for all-cause mortality, behaviour change, participants' views of the intervention and socioeconomic effects. Finally, we have identified three ongoing RCTs that are evaluating the efficacy and safety of metabolic and bariatric surgery in children and adolescents.
AUTHORS' CONCLUSIONS
Laparoscopic gastric banding led to greater body weight loss compared to a multi-component lifestyle program in one small study with 50 participants. These results have very limited application, primarily due to more recent recommendations derived from observation studies to avoid the use of banding in youth due to long-term reoperation rates. This systematic review update still highlights the lack of RCTs in this field. The authors are concerned that there may be ethical barriers to RTCs in this field, despite the lack of other effective therapies for severe obesity in children and adolescents and the significant morbidity and premature mortality caused by childhood obesity. Nevertheless, future studies, whether pre-registered and planned non-randomised or pragmatic randomised trials, should assess the impact of the surgical procedure and post-operative care to minimise adverse events, including the need for post-operative adjustments and revisional surgery. Long-term follow-up is also critical to comprehensively assess the impact of surgery as participants enter adulthood.
Topics: Adolescent; Adult; Australia; Child; Female; Humans; Life Style; Male; Pediatric Obesity; Quality of Life
PubMed: 36074911
DOI: 10.1002/14651858.CD011740.pub2 -
Critical Care Explorations Jul 2022To assess the pragmatism of published critical care randomized controlled trials self-described as pragmatic using a validated tool. (Review)
Review
UNLABELLED
To assess the pragmatism of published critical care randomized controlled trials self-described as pragmatic using a validated tool.
DATA SOURCES
Medical Literature Analysis and Retrieval Online database and PubMed interface from inception to November 1, 2021.
STUDY SELECTION
We performed a systematic search of randomized controlled trials evaluating interventions for critically ill adults that self-identified as pragmatic in title or abstract.
DATA EXTRACTION
Reviewers independently performed study selection and data extraction in duplicate; discrepancies were resolved by consensus. Pragmatism was assessed independently in duplicate by trained reviewers using the Pragmatic-Explanatory Continuum Indicator Summary 2 (PRECIS-2), a validated tool designed to represent how explanatory/pragmatic a trial is on the pragmatic to explanatory continuum. Trials were scored in nine domains on a 5-point continuum (from 1 = very explanatory to 5 = very pragmatic). Discrepancies of greater than 2 points were adjudicated by consensus discussion.
DATA SYNTHESIS
The search resulted in 284 studies; 56 met eligibility criteria. Forty-one of the trials had a discrepancy in at least one domain that required consensus discussion, most commonly in domains of eligibility and follow-up. Twelve studies (21.4%) were scored as "overall pragmatic," defined as score of greater than 4 in five domains provided the scores in the remaining domains were three. The overall PRECIS-2 score of self-identified pragmatic studies increased from 1995 to 2021 suggesting increasing pragmatism over time. Pragmatic trials were more likely to have a waiver of informed consent ( = 0.05).
CONCLUSIONS
The number and pragmatism of self-identified pragmatic trials have increased, particularly in the past decade. However, less than one-quarter of these trials that use the term pragmatic in title or abstract were retrospectively rated as pragmatic. Our results support the concept that trials are designed on a spectrum of pragmatic to explanatory. Advances in the design and reporting of critical care trials are needed to ensure their real-world applicability.
PubMed: 35923590
DOI: 10.1097/CCE.0000000000000738 -
Psychology & Health Jul 2022Reporting of the content and delivery characteristics of comparator interventions in published articles is often incomplete. This study examines the feasibility and...
OBJECTIVE
Reporting of the content and delivery characteristics of comparator interventions in published articles is often incomplete. This study examines the feasibility and validity of two methods for collecting additional information on comparator interventions from trial authors.
METHODS & MEASURES
In a systematic review of smoking cessation trials (IC-Smoke), all trial authors were asked to send unpublished comparator intervention materials and complete a specially-developed comparator intervention checklist. All published and additionally obtained information from authors were coded for behaviour change techniques (BCTs) and other characteristics (type of comparator, provider, provider training, delivery mode and treatment duration). To assess representativeness, we assessed the amount of additional information obtained from trial authors compared with the amount that was published. We examined known-group and convergent validity of comparator intervention data when using only published or also unpublished information.
RESULTS
Additional information were obtained from 91/136 (67%) of trial authors. Representativeness, known-group and convergent validity improved substantially based on the data collected by means of the comparator intervention checklist, but not by requesting authors to send any existing comparator materials.
CONCLUSIONS
Requesting authors for unpublished comparator intervention data, using specially-developed checklists and unpublished materials, substantially improves the quality of data available for systematic reviews.
PubMed: 35876093
DOI: 10.1080/08870446.2022.2081688 -
JAMA Oncology Sep 2022The log-rank test is considered the criterion standard for comparing 2 survival curves in pivotal registrational trials. However, with novel immunotherapies that often... (Meta-Analysis)
Meta-Analysis
Log-Rank Test vs MaxCombo and Difference in Restricted Mean Survival Time Tests for Comparing Survival Under Nonproportional Hazards in Immuno-oncology Trials: A Systematic Review and Meta-analysis.
IMPORTANCE
The log-rank test is considered the criterion standard for comparing 2 survival curves in pivotal registrational trials. However, with novel immunotherapies that often violate the proportional hazards assumptions over time, log-rank can lose power and may fail to detect treatment benefit. The MaxCombo test, a combination of weighted log-rank tests, retains power under different types of nonproportional hazards. The difference in restricted mean survival time (dRMST) test is frequently proposed as an alternative to the log-rank under nonproportional hazard scenarios.
OBJECTIVE
To compare the log-rank with the MaxCombo and dRMST in immuno-oncology trials to evaluate their performance in practice.
DATA SOURCES
Comprehensive literature review using Google Scholar, PubMed, and other sources for randomized clinical trials published in peer-reviewed journals or presented at major clinical conferences before December 2019 assessing efficacy of anti-programmed cell death protein-1 or anti-programmed death/ligand 1 monoclonal antibodies.
STUDY SELECTION
Pivotal studies with overall survival or progression-free survival as the primary or key secondary end point with a planned statistical comparison in the protocol. Sixty-three studies on anti-programmed cell death protein-1 or anti-programmed death/ligand 1 monoclonal antibodies used as monotherapy or in combination with other agents in 35 902 patients across multiple solid tumor types were identified.
DATA EXTRACTION AND SYNTHESIS
Statistical comparisons (n = 150) were made between the 3 tests using the analysis populations as defined in the original protocol of each trial.
MAIN OUTCOMES AND MEASURES
Nominal significance based on a 2-sided .05-level test was used to evaluate concordance. Case studies featuring different types of nonproportional hazards were used to discuss more robust ways of characterizing treatment benefit instead of sole reliance on hazard ratios.
RESULTS
In this systematic review and meta-analysis of 63 studies including 35 902 patients, between the log-rank and MaxCombo, 135 of 150 comparisons (90%) were concordant; MaxCombo achieved nominal significance in 15 of 15 discordant cases, while log-rank did not. Several cases appeared to have clinically meaningful benefits that would not have been detected using log-rank. Between the log-rank and dRMST tests, 137 of 150 comparisons (91%) were concordant; log-rank was nominally significant in 5 of 13 cases, while dRMST was significant in 8 of 13. Among all 3 tests, 127 comparisons (85%) were concordant.
CONCLUSIONS AND RELEVANCE
The findings of this review show that MaxCombo may provide a pragmatic alternative to log-rank when departure from proportional hazards is anticipated. Both tests resulted in the same statistical decision in most comparisons. Discordant studies had modest to meaningful improvements in treatment effect. The dRMST test provided no added sensitivity for detecting treatment differences over log-rank.
Topics: Antibodies, Monoclonal; Humans; Ligands; Neoplasms; Proportional Hazards Models; Survival Analysis; Survival Rate
PubMed: 35862037
DOI: 10.1001/jamaoncol.2022.2666 -
Clinical Trials (London, England) Aug 2022There are increasing pressures for anonymised datasets from clinical trials to be shared across the scientific community, and differing recommendations exist on how to...
BACKGROUND/AIMS
There are increasing pressures for anonymised datasets from clinical trials to be shared across the scientific community, and differing recommendations exist on how to perform anonymisation prior to sharing. We aimed to systematically identify, describe and synthesise existing recommendations for anonymising clinical trial datasets to prepare for data sharing.
METHODS
We systematically searched MEDLINE, EMBASE and Web of Science from inception to 8 February 2021. We also searched other resources to ensure the comprehensiveness of our search. Any publication reporting recommendations on anonymisation to enable data sharing from clinical trials was included. Two reviewers independently screened titles, abstracts and full text for eligibility. One reviewer extracted data from included papers using thematic synthesis, which then was sense-checked by a second reviewer. Results were summarised by narrative analysis.
RESULTS
Fifty-nine articles (from 43 studies) were eligible for inclusion. Three distinct themes are emerging: anonymisation, de-identification and pseudonymisation. The most commonly used anonymisation techniques are: removal of direct patient identifiers; and careful evaluation and modification of indirect identifiers to minimise the risk of identification. Anonymised datasets joined with controlled access was the preferred method for data sharing.
CONCLUSIONS
There is no single standardised set of recommendations on how to anonymise clinical trial datasets for sharing. However, this systematic review shows a developing consensus on techniques used to achieve anonymisation. Researchers in clinical trials still consider that anonymisation techniques by themselves are insufficient to protect patient privacy, and they need to be paired with controlled access.
Topics: Confidentiality; Data Anonymization; Humans; Information Dissemination; Research Personnel
PubMed: 35730910
DOI: 10.1177/17407745221087469 -
The Patient Nov 2022Patient support programs aim to provide solutions beyond the medication itself, by enhancing treatment adherence, improving clinical outcomes, elevating patient...
BACKGROUND AND OBJECTIVE
Patient support programs aim to provide solutions beyond the medication itself, by enhancing treatment adherence, improving clinical outcomes, elevating patient experience, and/or increasing quality of life. As patient support programs increasingly play an important role in assisting patients, numerous observational studies and pragmatic trials designed to evaluate their impact on healthcare have been conducted in recent years. This review aims to characterize these studies.
METHODS
A systematic literature review, supplemented by a broad search of gray literature, was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane recommendations. Observational studies and pragmatic trials conducted in Europe to evaluate the impact of patient support programs, published in English or Spanish between 17/03/2010 and 17/03/2020, were reviewed. Two patient support program definitions were applied starting with Ganguli et al.'s broad approach, followed by the European Medicines Agency definition, narrowed to Marketing Authorization Holders organized systems and their medicines. The quality of publications was assessed using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement 22-item checklist.
RESULTS
Of the 49 identified studies following the Ganguli et al. definition, 20 studies met the European Medicines Agency definition and were reviewed. Patient support program impact was evaluated based on a wide range of methodologies: 70% assessed patient support program-related patient-reported outcomes, 55% reported clinical outcomes, and 25% reported economic impacts on health resources. Only 45% conducted a comparative analysis. Overall, 75% of the studies achieved their proposed objectives.
CONCLUSIONS
The heterogeneity of the observational studies reviewed reflects the complexity of patient support programs that are built ad hoc for specific diseases, treatments, and patients. Results suggest that patient support programs play a key role in promoting treatment effectiveness, clinical outcomes, and satisfaction. However, there is a need for standardizing the definition of patient support programs and the methods to evaluate their impact.
Topics: Humans; Quality of Life; Checklist; Treatment Outcome; Europe
PubMed: 35725866
DOI: 10.1007/s40271-022-00582-y