Mental ill‐health in mothers of people with intellectual disabilities compared with mothers of typically developing people:A systematic review and meta‐analysis

Background: Mothers of people with intellectual disabilities (IDs) face exceptional challenges and may be more prone to experiencing mental ill‐health compared with mothers of typically developing people. These mental ill‐health problems may differ at different stages of the caregiving trajectory. However, there is no evidence synthesis on this topic. We aimed to systematically review evidence in this area and identify gaps in the existing literature. Method: Prospero registration: CRD42018088197. Medline, Embase, CINAHL and PsycINFO databases were searched. No time limits were applied. Studies were limited to English language. Inclusion criteria were studies of mothers of people with IDs that also included a comparison group of mothers of typically developing/developed children. Data were extracted from selected studies using a structured database. Study selection and quality appraisal were double rated. Where possible, meta‐analyses were performed. Results: Of the retrieved articles, 32/3089 were included, of which 10 reported on anxiety, 21 on depression and 23 on other indicators of mental ill‐health. Overall, previous studies reported that mothers of people with IDs experienced poorer mental health as compared with mothers of typically developing people. Meta‐analyses revealed significant findings for anxiety, depression, parenting stress, emotional burden and common mental disorders, but not for somatic symptoms. However, there was a considerable heterogeneity; hence, interpretation of results should be cautious. Identified gaps included scarce research on mental ill‐health of mothers of adults with IDs at different stages of the caregiving trajectory. Conclusions: There is evidence of poorer mental ill‐health in mothers of people with IDs compared with mothers of typically developing people, but lack of focus on different stages of the caregiving trajectory, methodological inconsistencies between studies and lack of robust studies pose limitations. This highlights the need both for improved support for mothers of people with IDs and for further methodologically robust research

Physical and mental health of young people with and without intellectual disabilities: cross-sectional analysis of a whole country population

Background: Transition to adulthood may be a period of vulnerability for health for individuals with intellectual disabilities. No large-scale studies have compared the health of individuals with and without intellectual disabilities undergoing transition. The aims of this study were (1) to compare health during transition for individuals with and without intellectual disabilities across a whole country population and (2) to establish whether transition is associated with health in the population with intellectual disabilities. Methods: Data were drawn from Scotland's Census, 2011. Frequency data were calculated for young people with and without intellectual disabilities. Logistic regressions were used to determine the extent to which intellectual disabilities account for seven health outcomes (general health, mental health, physical disabilities, hearing impairment, visual impairment, long-term illness and day-to-day activity limitations), adjusted for age and gender. Within the intellectual disabilities population, logistic regressions were then used to determine whether age group (13–18 or 19–24 years) is associated with the seven health outcomes, adjusted by gender. Results: A total of 5556/815 889 young people aged 13–24 years had intellectual disabilities. Those with intellectual disabilities were 9.6–125.0 times more likely to have poor health on the seven outcomes. Within the population with intellectual disabilities, the 19- to 24-year-olds with intellectual disabilities were more likely to have mental health problems than the 13- to 18-year-olds, but did not have poorer health on the other outcomes. The difference between age groups for mental health problems was greater for young people who did not have intellectual disabilities, but their overall level of mental health problems was substantially lower than for the young people with intellectual disabilities. Conclusions: This largest-to-date study quantifies the extent of the substantial health disparities experienced by young people with intellectual disabilities compared with people without intellectual disabilities. The young population with intellectual disabilities have substantial health problems; therefore, transition between child and adult services must be carefully planned in order to ensure that existing health conditions are managed and emerging problems minimised

The relative influence of intellectual disabilities and autism on sensory impairments and physical disability:A whole‐country cohort of 5.3 million children and adults

Background: Intellectual disabilities and autism are lifelong and often co‐occur. Little is known on their extent of independent association with sensory impairments and physical disability. Methods: For Scotland's population, logistic regressions investigated age–gender‐adjusted odds ratios (OR) of associations, independently, of intellectual disabilities and autism with sensory impairments and physical disability. Results: 1,548,819 children/youth, and 3,746,584 adults. In children/youth, the effect size of intellectual disabilities and autism, respectively, was as follows: blindness (OR = 30.12; OR = 2.63), deafness (OR = 13.98; OR = 2.31), and physical disability (OR = 43.72; OR = 5.62). For adults, the effect size of intellectual disabilities and autism, respectively, was as follows: blindness (OR = 16.89; OR = 3.29), deafness (OR = 7.47; OR = 2.36), and physical disability (OR = 6.04; OR = 3.16). Conclusions: Intellectual disabilities have greater association with the population burden of sensory impairments/physical disability, but autism is also associated regardless of overlap with intellectual disabilities. These may impact further on communication limitations due to autism and intellectual disabilities, increasing complexity of assessments/management of other health conditions. Clinicians need to be aware of these important issues

The Transition to Upper Secondary Level After Basic Education for Adolescents with Autism Spectrum Disorder in Finland

This chapter provides an exploration of the preparation of pupils with autism spectrum disorder (ASD) for transition to upper secondary level after Finnish basic education. It also examines the importance of supports required during the transition phase. Two examples of pupils with ASD (Kalle and Maija) are utilized to illustrate how to plan and support pupils with ASD during their initial post-school transition. Transitions are defined, after which education opportunities after basic education for pupils with ASD in Finland are examined. This is followed by a brief illustration of the Finnish comprehensive school system to provide context with a focus on support arrangements and the preparation of support for transition. Then, the individual transition-planning documents are examined, after which the two cases of Kalle and Maija are introduced. This is followed by an illustration of the use of the documents in practice for the two pupils. The summary includes a discussion of implications for future directions.Peer reviewe

Which patients with metastatic hormone-sensitive prostate cancer benefit from docetaxel: a systematic review and meta-analysis of individual participant data from randomised trials

BACKGROUND: Adding docetaxel to androgen deprivation therapy (ADT) improves survival in patients with metastatic, hormone-sensitive prostate cancer, but uncertainty remains about who benefits most. We therefore aimed to obtain up-to-date estimates of the overall effects of docetaxel and to assess whether these effects varied according to prespecified characteristics of the patients or their tumours. METHODS: The STOPCAP M1 collaboration conducted a systematic review and meta-analysis of individual participant data. We searched MEDLINE (from database inception to March 31, 2022), Embase (from database inception to March 31, 2022), the Cochrane Central Register of Controlled Trials (from database inception to March 31, 2022), proceedings of relevant conferences (from Jan 1, 1990, to Dec 31, 2022), and ClinicalTrials.gov (from database inception to March 28, 2023) to identify eligible randomised trials that assessed docetaxel plus ADT compared with ADT alone in patients with metastatic, hormone-sensitive prostate cancer. Detailed and updated individual participant data were requested directly from study investigators or through relevant repositories. The primary outcome was overall survival. Secondary outcomes were progression-free survival and failure-free survival. Overall pooled effects were estimated using an adjusted, intention-to-treat, two-stage, fixed-effect meta-analysis, with one-stage and random-effects sensitivity analyses. Missing covariate values were imputed. Differences in effect by participant characteristics were estimated using adjusted two-stage, fixed-effect meta-analysis of within-trial interactions on the basis of progression-free survival to maximise power. Identified effect modifiers were also assessed on the basis of overall survival. To explore multiple subgroup interactions and derive subgroup-specific absolute treatment effects we used one-stage flexible parametric modelling and regression standardisation. We assessed the risk of bias using the Cochrane Risk of Bias 2 tool. This study is registered with PROSPERO, CRD42019140591. FINDINGS: We obtained individual participant data from 2261 patients (98% of those randomised) from three eligible trials (GETUG-AFU15, CHAARTED, and STAMPEDE trials), with a median follow-up of 72 months (IQR 55-85). Individual participant data were not obtained from two additional small trials. Based on all included trials and patients, there were clear benefits of docetaxel on overall survival (hazard ratio [HR] 0·79, 95% CI 0·70 to 0·88; p<0·0001), progression-free survival (0·70, 0·63 to 0·77; p<0·0001), and failure-free survival (0·64, 0·58 to 0·71; p<0·0001), representing 5-year absolute improvements of around 9-11%. The overall risk of bias was assessed to be low, and there was no strong evidence of differences in effect between trials for all three main outcomes. The relative effect of docetaxel on progression-free survival appeared to be greater with increasing clinical T stage (pinteraction=0·0019), higher volume of metastases (pinteraction=0·020), and, to a lesser extent, synchronous diagnosis of metastatic disease (pinteraction=0·077). Taking into account the other interactions, the effect of docetaxel was independently modified by volume and clinical T stage, but not timing. There was no strong evidence that docetaxel improved absolute effects at 5 years for patients with low-volume, metachronous disease (-1%, 95% CI -15 to 12, for progression-free survival; 0%, -10 to 12, for overall survival). The largest absolute improvement at 5 years was observed for those with high-volume, clinical T stage 4 disease (27%, 95% CI 17 to 37, for progression-free survival; 35%, 24 to 47, for overall survival). INTERPRETATION: The addition of docetaxel to hormone therapy is best suited to patients with poorer prognosis for metastatic, hormone-sensitive prostate cancer based on a high volume of disease and potentially the bulkiness of the primary tumour. There is no evidence of meaningful benefit for patients with metachronous, low-volume disease who should therefore be managed differently. These results will better characterise patients most and, importantly, least likely to gain benefit from docetaxel, potentially changing international practice, guiding clinical decision making, better informing treatment policy, and improving patient outcomes. FUNDING: UK Medical Research Council and Prostate Cancer UK

Which patients with metastatic hormone-sensitive prostate cancer benefit from docetaxel: a systematic review and meta-analysis of individual participant data from randomised trials

© 2023 The Authors. Published by Elsevier. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1016/S1470-2045(23)00230-9Background Adding docetaxel to androgen deprivation therapy (ADT) improves survival in patients with metastatic, hormone-sensitive prostate cancer, but uncertainty remains about who benefits most. We therefore aimed to obtain up-to-date estimates of the overall effects of docetaxel and to assess whether these effects varied according to prespecified characteristics of the patients or their tumours. Methods The STOPCAP M1 collaboration conducted a systematic review and meta-analysis of individual participant data. We searched MEDLINE (from database inception to March 31, 2022), Embase (from database inception to March 31, 2022), the Cochrane Central Register of Controlled Trials (from database inception to March 31, 2022), proceedings of relevant conferences (from Jan 1, 1990, to Dec 31, 2022), and ClinicalTrials.gov (from database inception to March 28, 2023) to identify eligible randomised trials that assessed docetaxel plus ADT compared with ADT alone in patients with metastatic, hormone-sensitive prostate cancer. Detailed and updated individual participant data were requested directly from study investigators or through relevant repositories. The primary outcome was overall survival. Secondary outcomes were progression-free survival and failure-free survival. Overall pooled effects were estimated using an adjusted, intention-to-treat, two-stage, fixed-effect meta-analysis, with one-stage and random-effects sensitivity analyses. Missing covariate values were imputed. Differences in effect by participant characteristics were estimated using adjusted two-stage, fixed-effect meta-analysis of within-trial interactions on the basis of progression-free survival to maximise power. Identified effect modifiers were also assessed on the basis of overall survival. To explore multiple subgroup interactions and derive subgroup-specific absolute treatment effects we used one-stage flexible parametric modelling and regression standardisation. We assessed the risk of bias using the Cochrane Risk of Bias 2 tool. This study is registered with PROSPERO, CRD42019140591. Findings We obtained individual participant data from 2261 patients (98% of those randomised) from three eligible trials (GETUG-AFU15, CHAARTED, and STAMPEDE trials), with a median follow-up of 72 months (IQR 55–85). Individual participant data were not obtained from two additional small trials. Based on all included trials and patients, there were clear benefits of docetaxel on overall survival (hazard ratio [HR] 0·79, 95% CI 0·70 to 0·88; p<0·0001), progression-free survival (0·70, 0·63 to 0·77; p<0·0001), and failure-free survival (0·64, 0·58 to 0·71; p<0·0001), representing 5-year absolute improvements of around 9–11%. The overall risk of bias was assessed to be low, and there was no strong evidence of differences in effect between trials for all three main outcomes. The relative effect of docetaxel on progression-free survival appeared to be greater with increasing clinical T stage (pinteraction=0·0019), higher volume of metastases (pinteraction=0·020), and, to a lesser extent, synchronous diagnosis of metastatic disease (pinteraction=0·077). Taking into account the other interactions, the effect of docetaxel was independently modified by volume and clinical T stage, but not timing. There was no strong evidence that docetaxel improved absolute effects at 5 years for patients with low-volume, metachronous disease (–1%, 95% CI –15 to 12, for progression-free survival; 0%, –10 to 12, for overall survival). The largest absolute improvement at 5 years was observed for those with high-volume, clinical T stage 4 disease (27%, 95% CI 17 to 37, for progression-free survival; 35%, 24 to 47, for overall survival). Interpretation The addition of docetaxel to hormone therapy is best suited to patients with poorer prognosis for metastatic, hormone-sensitive prostate cancer based on a high volume of disease and potentially the bulkiness of the primary tumour. There is no evidence of meaningful benefit for patients with metachronous, low-volume disease who should therefore be managed differently. These results will better characterise patients most and, importantly, least likely to gain benefit from docetaxel, potentially changing international practice, guiding clinical decision making, better informing treatment policy, and improving patient outcomes.This study was funded by the UK Research and Innovation Medical Research Council (grant number MC_UU_00004/06, to support CLV, DJF, LHR, ER, SB, JFT, IRW, and MKBP) and by Prostate Cancer UK (grant number RIA 16-ST2-020, awarded to JFT, to support DJF, LHR, PJG, and ER). PJG is partly supported by the UK National Institute for Health Research and Care's Development and Skills Enhancement Award (NIHR301653).Published versio

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial.

Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy.This article is freely available via Open Access