Vedolizumab for induction and maintenance of remission in Crohn's disease.

BACKGROUND: Vedolizumab blocks inflammatory activity within the gastrointestinal tract. Systematic reviews have demonstrated the efficacy of vedolizumab in ulcerative colitis and inflammatory bowel disease in general. This systematic review and meta-analysis summarises the current evidence of vedolizumab in the induction and maintenance of remission in Crohn's disease. OBJECTIVES: To evaluate the benefits and harms of vedolizumab versus placebo for the induction and maintenance of remission in people with Crohn's disease. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 30 November 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing vedolizumab to placebo for the induction or maintenance of remission in people with Crohn's disease. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. For induction studies, the primary outcome was 1. clinical remission, and secondary outcomes were rates of 2. clinical response, 3. adverse events, 4. serious adverse events, 5. surgery, 6. endoscopic remission and 7. endoscopic response. For maintenance studies, the primary outcome was 1. maintenance of clinical remission, and secondary outcomes were rates of 2. adverse events, 3. serious adverse events, 4. surgery, 5. endoscopic remission and 6. endoscopic response. We used GRADE to assess certainty of evidence. MAIN RESULTS: We analysed induction (4 trials, 1126 participants) and maintenance (3 trials, 894 participants) studies representing people across North America, Europe, Asia and Australasia separately. One maintenance trial administered subcutaneous vedolizumab whilst the other studies used the intravenous form. The mean age ranged between 32.6 and 38.6 years. Vedolizumab was superior to placebo for the induction of clinical remission (71 more per 1000 with clinical remission with vedolizumab; risk ratio (RR) 1.61, 95% confidence interval (CI) 1.20 to 2.17; number needed to treat for an additional beneficial outcome (NNTB) 13; 4 studies; high-certainty evidence) and superior to placebo for inducing clinical response (105 more per 1000 with clinical response with vedolizumab; RR 1.43, 95% CI 1.19 to 1.71; NNTB 8; 4 studies; high-certainty evidence). For the induction phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (9 fewer serious adverse events per 1000 with vedolizumab; RR 0.91, 95% CI 0.62 to 1.33; 4 studies; low-certainty evidence) and probably equivalent to placebo for overall adverse events (6 fewer adverse events per 1000 with vedolizumab; RR 1.01, 95% CI 0.93 to 1.11; 4 studies; moderate-certainty evidence). Vedolizumab was superior to placebo for the maintenance of clinical remission (141 more per 1000 with maintenance of clinical remission with vedolizumab; RR 1.52, 95% CI 1.24 to 1.87; NNTB 7; 3 studies; high-certainty evidence). During the maintenance phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (3 fewer serious adverse events per 1000 with vedolizumab; RR 0.98, 95% CI 0.68 to 1.39; 3 studies; low-certainty evidence) and probably equivalent to placebo for the development of overall adverse events (0 difference in adverse events per 1000; RR 1.00, 95% CI 0.94 to 1.07; 3 studies; moderate-certainty evidence). AUTHORS' CONCLUSIONS: High-certainty data across four induction and three maintenance trials demonstrate that vedolizumab is superior to placebo in the induction and maintenance of remission in Crohn's disease. Overall adverse events are probably similar and serious adverse events may be similar between vedolizumab and placebo during both induction and maintenance phases of treatment. Head-to-head research comparing the efficacy and safety of vedolizumab to other biological therapies is required.

Cognitive behavioural therapy (group) for schizophrenia.

BACKGROUND: Schizophrenia is a disabling psychotic disorder characterised by positive symptoms of delusions, hallucinations, disorganised speech and behaviour; and negative symptoms such as affective flattening and lack of motivation. Cognitive behavioural therapy (CBT) is a psychological intervention that aims to change the way in which a person interprets and evaluates their experiences, helping them to identify and link feelings and patterns of thinking that underpin distress. CBT models targeting symptoms of psychosis (CBTp) have been developed for many mental health conditions including schizophrenia. CBTp has been suggested as a useful add-on therapy to medication for people with schizophrenia. While CBT for people with schizophrenia was mainly developed as an individual treatment, it is expensive and a group approach may be more cost-effective. Group CBTp can be defined as a group intervention targeting psychotic symptoms, based on the cognitive behavioural model. In group CBTp, people work collaboratively on coping with distressing hallucinations, analysing evidence for their delusions, and developing problem-solving and social skills. However, the evidence for effectiveness is far from conclusive. OBJECTIVES: To investigate efficacy and acceptability of group CBT applied to psychosis compared with standard care or other psychosocial interventions, for people with schizophrenia or schizoaffective disorder. SEARCH METHODS: On 10 February 2021, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, four other databases and two trials registries. We handsearched the reference lists of relevant papers and previous systematic reviews and contacted experts in the field for supplemental data. SELECTION CRITERIA: We selected randomised controlled trials allocating adults with schizophrenia to receive either group CBT for schizophrenia, compared with standard care, or any other psychosocial intervention (group or individual). DATA COLLECTION AND ANALYSIS: We complied with Cochrane recommended standard of conduct for data screening and collection. Where possible, we calculated risk ratio (RR) and 95% confidence interval (CI) for binary data and mean difference (MD) and 95% CI for continuous data. We used a random-effects model for analyses. We assessed risk of bias for included studies and created a summary of findings table using GRADE. MAIN RESULTS: The review includes 24 studies (1900 participants). All studies compared group CBTp with treatments that a person with schizophrenia would normally receive in a standard mental health service (standard care) or any other psychosocial intervention (group or individual). None of the studies compared group CBTp with individual CBTp. Overall risk of bias within the trials was moderate to low. We found no studies reporting data for our primary outcome of clinically important change. With regard to numbers of participants leaving the study early, group CBTp has little or no effect compared to standard care or other psychosocial interventions (RR 1.22, 95% CI 0.94 to 1.59; studies = 13, participants = 1267; I2 = 9%; low-certainty evidence). Group CBTp may have some advantage over standard care or other psychosocial interventions for overall mental state at the end of treatment for endpoint scores on the Positive and Negative Syndrome Scale (PANSS) total (MD -3.73, 95% CI -4.63 to -2.83; studies = 12, participants = 1036; I2 = 5%; low-certainty evidence). Group CBTp seems to have little or no effect on PANSS positive symptoms (MD -0.45, 95% CI -1.30 to 0.40; studies =8, participants = 539; I2 = 0%) and on PANSS negative symptoms scores at the end of treatment (MD -0.73, 95% CI -1.68 to 0.21; studies = 9, participants = 768; I2 = 65%). Group CBTp seems to have an advantage over standard care or other psychosocial interventions on global functioning measured by Global Assessment of Functioning (GAF; MD -3.61, 95% CI -6.37 to -0.84; studies = 5, participants = 254; I2 = 0%; moderate-certainty evidence), Personal and Social Performance Scale (PSP; MD 3.30, 95% CI 2.00 to 4.60; studies = 1, participants = 100), and Social Disability Screening Schedule (SDSS; MD -1.27, 95% CI -2.46 to -0.08; studies = 1, participants = 116). Service use data were equivocal with no real differences between treatment groups for number of participants hospitalised (RR 0.78, 95% CI 0.38 to 1.60; studies = 3, participants = 235; I2 = 34%). There was no clear difference between group CBTp and standard care or other psychosocial interventions endpoint scores on depression and quality of life outcomes, except for quality of life measured by World Health Organization Quality of Life Assessment Instrument (WHOQOL-BREF) Psychological domain subscale (MD -4.64, 95% CI -9.04 to -0.24; studies = 2, participants = 132; I2 = 77%). The studies did not report relapse or adverse effects. AUTHORS' CONCLUSIONS: Group CBTp appears to be no better or worse than standard care or other psychosocial interventions for people with schizophrenia in terms of leaving the study early, service use and general quality of life. Group CBTp seems to be more effective than standard care or other psychosocial interventions on overall mental state and global functioning scores. These results may not be widely applicable as each study had a low sample size. Therefore, no firm conclusions concerning the efficacy of group CBTp for people with schizophrenia can currently be made. More high-quality research, reporting useable and relevant data is needed.

Avatar Therapy for people with schizophrenia or related disorders.

BACKGROUND: Many people with schizophrenia do not achieve satisfactory improvements in their mental state, particularly the symptom of hearing voices (hallucinations), with medical treatment. OBJECTIVES: To examine the effects of Avatar Therapy for people with schizophrenia or related disorders. SEARCH METHODS: In December 2016, November 2018 and April 2019, the Cochrane Schizophrenia Group's Study-Based Register of Trials (including registries of clinical trials) was searched, review authors checked references of all identified relevant reports to identify more studies and contacted authors of trials for additional information. SELECTION CRITERIA: All randomised clinical trials focusing on Avatar Therapy for people with schizophrenia or related disorders. DATA COLLECTION AND ANALYSIS: We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and 95% confidence intervals (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and 95% CIs. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. Our main outcomes of interest were clinically important change in; mental state, insight, global state, quality of life and functioning as well as adverse effects and leaving the study early. MAIN RESULTS: We found 14 potentially relevant references for three studies (participants = 195) comparing Avatar Therapy with two other interventions; treatment as usual or supportive counselling. Both Avatar Therapy and supportive counselling were given in addition (add-on) to the participants' normal care. All of the studies had high risk of bias across one or more domains for methodology and, for other risks of bias, authors from one of the studies were involved in the development of the avatar systems on trial and in another trial, authors had patents on the avatar system pending. 1. Avatar Therapy compared with treatment as usual When Avatar Therapy was compared with treatment as usual average endpoint Positive and Negative Syndrome Scale - Positive (PANSS-P) scores were not different between treatment groups (MD -1.93, 95% CI -5.10 to 1.24; studies = 1, participants = 19; very low-certainty evidence). A measure of insight (Revised Beliefs about Voices Questionnaire; BAVQ-R) showed an effect in favour of Avatar Therapy (MD -5.97, 95% CI -10.98 to -0.96; studies = 1, participants = 19; very low-certainty evidence). No one was rehospitalised in either group in the short term (risk difference (RD) 0.00, 95% CI -0.20 to 0.20; studies = 1, participants = 19; low-certainty evidence). Numbers leaving the study early from each group were not clearly different - although more did leave from the Avatar Therapy group (6/14 versus 0/12; RR 11.27, 95% CI 0.70 to 181.41; studies = 1, participants = 26; low-certainty evidence). There was no clear difference in anxiety between treatment groups (RR 5.54, 95% CI 0.34 to 89.80; studies = 1, participants = 19; low-certainty evidence). For quality of life, average Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (QLESQ-SF) scores favoured Avatar Therapy (MD 9.99, 95% CI 3.89 to 16.09; studies = 1, participants = 19; very low-certainty evidence). No study reported data for functioning. 2. Avatar Therapy compared with supportive counselling When Avatar Therapy was compared with supportive counselling (all short-term), general mental state (Psychotic Symptom Rating Scale (PSYRATS)) scores favoured the Avatar Therapy group (MD -4.74, 95% CI -8.01 to -1.47; studies = 1, participants = 124; low-certainty evidence). For insight (BAVQ-R), there was a small effect in favour of Avatar Therapy (MD -8.39, 95% CI -14.31 to -2.47; studies = 1, participants = 124; low-certainty evidence). Around 20% of each group left the study early (risk ratio (RR) 1.06, 95% CI 0.59 to 1.89; studies = 1, participants = 150; moderate-certainty evidence). Analysis of quality of life scores (Manchester Short Assessment of Quality of Life (MANSA)) showed no clear difference between groups (MD 2.69, 95% CI -1.48 to 6.86; studies = 1, participants = 120; low-certainty evidence). No data were available for rehospitalisation rates, adverse events or functioning. AUTHORS' CONCLUSIONS: Our analyses of available data shows few, if any, consistent effects of Avatar Therapy for people living with schizophrenia who experience auditory hallucinations. Where there are effects, or suggestions of effects, we are uncertain because of their risk of bias and their unclear clinical meaning. The theory behind Avatar Therapy is compelling but the practice needs testing in large, long, well-designed, well-reported randomised trials undertaken with help from - but not under the direction of - Avatar Therapy pioneers.

Penicillin Allergy Testing and Delabeling for Patients Who Are Prescribed Penicillin: A Systematic Review for a World Health Organization Guideline.

Secondary prevention with penicillin aims to prevent further episodes of acute rheumatic fever and subsequent development of rheumatic heart disease (RHD). Penicillin allergy, self-reported by 10% of the population, can affect secondary prevention programs. We aimed to assess the role for (i) routine penicillin allergy testing and the (ii) safety of penicillin allergy delabeling approaches in this context. We searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, ISRCTN, and CPCI-S to identify the relevant reports. We found 2419 records, but no studies addressed our initial question. Following advice from the WHO-Guideline committee and experts, we identified 6 manuscripts on allergy testing focusing on other populations showing that the prevalence of allergy confirmed by testing was low and the incidence of life-threatening reactions to BPG was very low (< 1-3/1000 individuals treated). A subsequent search addressed penicillin allergy delabeling. This found 516 records, and 5 studies addressing the safety of direct oral drug challenge vs. skin testing followed by drug administration in patients with suspected penicillin allergy. Immediate allergic reactions of minor severity were observed for a minority of patients and occurred less frequently in the direct drug challenge group: 2.3% vs. 11.5%; RR = 0.25, 95%CI 0.15-0.45, P < 0.00001, I2 = 0%. No anaphylaxis or deaths were observed. Severe allergic reactions to penicillin are extremely rare and can be recognized and dealt by trained healthcare workers. Confirmation of penicillin allergy diagnosis or delabeling using direct oral drug challenge or penicillin skin testing seems to be safe and is associated with a low rate of adverse reactions.

Handheld echocardiography for the screening and diagnosis of rheumatic heart disease: a systematic review to inform WHO guidelines.

BACKGROUND: Early detection and diagnosis of acute rheumatic fever and rheumatic heart disease are key to preventing progression, and echocardiography has an important diagnostic role. Standard echocardiography might not be feasible in high-prevalence regions due to its high cost, complexity, and time requirement. Handheld echocardiography might be an easy-to-use, low-cost alternative, but its performance in screening for and diagnosing acute rheumatic fever and rheumatic heart disease needs further investigation. METHODS: In this systematic review and meta-analysis, we searched Embase, MEDLINE, LILACS, and Conference Proceedings Citation Index-Science up to Feb 9, 2024, for studies on the screening and diagnosis of acute rheumatic fever and rheumatic heart disease using handheld echocardiography (index test) or standard echocardiography or auscultation (reference tests) in high-prevalence areas. We included all studies with useable data in which the diagnostic performance of the index test was assessed against a reference test. Data on test accuracy in diagnosing rheumatic heart disease, acute rheumatic fever, or carditis with acute rheumatic fever (primary outcomes) were extracted from published articles or calculated, with authors contacted as necessary. Quality of evidence was appraised using GRADE and QUADAS-2 criteria. We summarised diagnostic accuracy statistics (including sensitivity and specificity) and estimated 95% CIs using a bivariate random-effects model (or univariate random-effects models for analyses including three or fewer studies). Area under the curve (AUC) was calculated from summary receiver operating characteristic curves. Heterogeneity was assessed by visual inspection of plots. This study was registered with PROSPERO (CRD42022344081). FINDINGS: Out of 4868 records we identified 11 studies, and two additional reports, comprising 15 578 unique participants. Pooled data showed that handheld echocardiography had high sensitivity (0·87 [95% CI 0·76-0·93]), specificity (0·98 [0·71-1·00]), and overall high accuracy (AUC 0·94 [0·84-1·00]) for diagnosing rheumatic heart disease when compared with standard echocardiography (two studies; moderate certainty of evidence), with better performance for diagnosing definite compared with borderline rheumatic heart disease. High sensitivity (0·79 [0·73-0·84]), specificity (0·85 [0·80-0·89]), and overall accuracy (AUC 0·90 [0·85-0·94]) for screening rheumatic heart disease was observed when pooling data of handheld echocardiography versus standard echocardiography (seven studies; high certainty of evidence). Most studies had a low risk of bias overall. Some heterogeneity was observed for sensitivity and specificity across studies, possibly driven by differences in the prevalence and severity of rheumatic heart disease, and level of training or expertise of non-expert operators. INTERPRETATION: Handheld echocardiography has a high accuracy and diagnostic performance when compared with standard echocardiography for diagnosing and screening of rheumatic heart disease in high-prevalence areas. FUNDING: World Health Organization. TRANSLATIONS: For the Chinese, French, Italian, Persian, Portuguese, Spanish and Urdu translations of the abstract see Supplementary Materials section.

Post-stroke fatigue: a scoping review.

Background: Post-stroke fatigue (PSF) is one of the most common and frustrating outcomes of stroke. It has a high prevalence and it can persist for many years after stroke. PSF itself contributes to a wider range of undesirable outcomes that affect all aspects of daily life. The aim of this review was to identify and summarise the most recent research on PSF, in order to update the evidence base. Methods: We updated an existing review (Hinkle et al. 2017) systematically searching CINAHL, MEDLINE, PsycINFO, and PubMed to cover new research studies between 1 st March 2016 and the search date (19 th January 2020). We included interventional and observational research, and clinical practice guidelines that were not covered in the original review. After duplicate removal in EndNote, two reviewers screened the search results in Rayyan, and data from eligible full texts were extracted onto an Excel spreadsheet. Finally, we used RobotReviewer and a human reviewer to assess the risk of bias of randomised trials for this scoping review. Results: We identified 45 records for 30 studies (14 observational, 10 interventional studies, and 6 guidelines). Apart from one, the interventional studies were single-centred, had high risk of bias and small sample size (median 50). They investigated exercise, pharmacotherapy, psychotherapy, education, and light therapy. Observational studies mainly reported the factors related to PSF including co-morbidities, depression and anxiety, quality of life, activities of daily living, stroke severity, medication use and polypharmacy, polymorphism, pain, apathy, limb heaviness, neuroticism, mobility, and thyroid-stimulating hormone. Guidelines either did not report on PSF or, when reported, their recommendations were supported by little or low level of evidence. Conclusion: Although we identified a number of recent studies which have added to our current knowledge on PSF, none are robust enough to change current clinical practice.