Bradford Teaching Hospitals NHS Foundation Trust

This meta-analysis explored the efficacy of the Theory of Planned Behaviour (TPB) dependent on behaviour and methodological moderators. A lack of hierarchical analysis in previous reviews risks confounding these moderators. Here moderating roles of behaviour type, length of follow-up, sample age and behavioural measure are explored hierarchically amongst prospective tests of the TPB, controlling for past behaviour where possible. Searching identified 237 prospective tests from 206 articles. Random-effects meta-analytic procedures were used to correcting correlations for sampling and measurement error. Behaviour type moderated the model; physical activity and diet behaviours were better predicted (23.9% and 21.2% variance explained, respectively) whilst risk, detection, safer sex and abstinence from drugs were poorly predicted (between 13.8 and 15.3% variance explained). Methodological moderators were also apparent: age of sample moderated relations with student samples better predicted for physical activity, and adolescent samples better predicted for abstinence behaviours. Behaviours assessed in the shorter term, and those assessed with self-reports (compared with objective measures) were also better predicted. Both behavioural and methodological characteristics moderated relations amongst model components. The results can aid selection of appropriate targets upon which to base interventions.

BACKGROUND: Intravenous bolus fluorouracil plus leucovorin is the standard adjuvant treatment for colon cancer. The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer. We evaluated capecitabine in the adjuvant setting. METHODS: We randomly assigned a total of 1987 patients with resected stage III colon cancer to receive either oral capecitabine (1004 patients) or bolus fluorouracil plus leucovorin (Mayo Clinic regimen; 983 patients) over a period of 24 weeks. The primary efficacy end point was at least equivalence in disease-free survival; the primary safety end point was the incidence of grade 3 or 4 toxic effects due to fluoropyrimidines. RESULTS: Disease-free survival in the capecitabine group was at least equivalent to that in the fluorouracil-plus-leucovorin group (in the intention-to-treat analysis, P<0.001 for the comparison of the upper limit of the hazard ratio with the noninferiority margin of 1.20). Capecitabine improved relapse-free survival (hazard ratio, 0.86; 95 percent confidence interval, 0.74 to 0.99; P=0.04) and was associated with significantly fewer adverse events than fluorouracil plus leucovorin (P<0.001). CONCLUSIONS: Oral capecitabine is an effective alternative to intravenous fluorouracil plus leucovorin in the adjuvant treatment of colon cancer.

Patients with neuropathic pain secondary to failed back surgery syndrome (FBSS) typically experience persistent pain, disability, and reduced quality of life. We hypothesised that spinal cord stimulation (SCS) is an effective therapy in addition to conventional medical management (CMM) in this patient population. We randomised 100 FBSS patients with predominant leg pain of neuropathic radicular origin to receive spinal cord stimulation plus conventional medical management (SCS group) or conventional medical management alone (CMM group) for at least 6 months. The primary outcome was the proportion of patients achieving 50% or more pain relief in the legs. Secondary outcomes were improvement in back and leg pain, health-related quality of life, functional capacity, use of pain medication and non-drug pain treatment, level of patient satisfaction, and incidence of complications and adverse effects. Crossover after the 6-months visit was permitted, and all patients were followed up to 1 year. In the intention-to-treat analysis at 6 months, 24 SCS patients (48%) and 4 CMM patients (9%) (p<0.001) achieved the primary outcome. Compared with the CMM group, the SCS group experienced improved leg and back pain relief, quality of life, and functional capacity, as well as greater treatment satisfaction (p<or=0.05 for all comparisons). Between 6 and 12 months, 5 SCS patients crossed to CMM, and 32 CMM patients crossed to SCS. At 12 months, 27 SCS patients (32%) had experienced device-related complications. In selected patients with FBSS, SCS provides better pain relief and improves health-related quality of life and functional capacity compared with CMM alone.

Abstract The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

OBJECTIVE: To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with psoriatic arthritis (PsA). METHODS: GRAPPA rheumatologists, dermatologists, and PsA patients drafted overarching principles for the management of PsA, based on consensus achieved at face-to-face meetings and via online surveys. We conducted literature reviews regarding treatment for the key domains of PsA (arthritis, spondylitis, enthesitis, dactylitis, skin disease, and nail disease) and convened a new group to identify pertinent comorbidities and their effect on treatment. Finally, we drafted treatment recommendations for each of the clinical manifestations and assessed the level of agreement for the overarching principles and treatment recommendations among GRAPPA members, using an online questionnaire. RESULTS: Six overarching principles had ≥80% agreement among both health care professionals (n = 135) and patient research partners (n = 10). We developed treatment recommendations and a schema incorporating these principles for arthritis, spondylitis, enthesitis, dactylitis, skin disease, nail disease, and comorbidities in the setting of PsA, using the Grading of Recommendations, Assessment, Development and Evaluation process. Agreement of >80% was reached for approval of the individual recommendations and the overall schema. CONCLUSION: We present overarching principles and updated treatment recommendations for the key manifestations of PsA, including related comorbidities, based on a literature review and consensus of GRAPPA members (rheumatologists, dermatologists, other health care providers, and patient research partners). Further updates are anticipated as the therapeutic landscape in PsA evolves.

BACKGROUND: Reasoned action approach (RAA) includes subcomponents of attitude (experiential/instrumental), perceived norm (injunctive/descriptive), and perceived behavioral control (capacity/autonomy) to predict intention and behavior. PURPOSE: To provide a meta-analysis of the RAA for health behaviors focusing on comparing the pairs of RAA subcomponents and differences between health protection and health-risk behaviors. METHODS: The present research reports a meta-analysis of correlational tests of RAA subcomponents, examination of moderators, and combined effects of subcomponents on intention and behavior. Regressions were used to predict intention and behavior based on data from studies measuring all variables. RESULTS: Capacity and experiential attitude had large, and other constructs had small-medium-sized correlations with intention; all constructs except autonomy were significant independent predictors of intention in regressions. Intention, capacity, and experiential attitude had medium-large, and other constructs had small-medium-sized correlations with behavior; intention, capacity, experiential attitude, and descriptive norm were significant independent predictors of behavior in regressions. CONCLUSIONS: The RAA subcomponents have utility in predicting and understanding health behaviors.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterised by infrequent or absent ovulation, and high levels of androgens and insulin (hyperinsulinaemia). Hyperinsulinaemia occurs secondary to insulin resistance and is associated with increased risk of cardiovascular disease and diabetes mellitus. Insulin-sensitising agents such as metformin may be effective in treating PCOS-related anovulation. OBJECTIVES: To evaluate the effectiveness and safety of insulin-sensitising drugs in improving reproductive and metabolic outcomes for women with PCOS undergoing ovulation induction. SEARCH METHODS: We searched the following databases from inception to January 2017: Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL. We searched registers of ongoing trials and reference lists from relevant studies. SELECTION CRITERIA: We included randomised controlled trials of insulin-sensitising drugs compared with placebo, no treatment, or an ovulation-induction agent for women with oligo and anovulatory PCOS. DATA COLLECTION AND ANALYSIS: statistic and reported quality of the evidence for primary outcomes using GRADE methodology. MAIN RESULTS: = 52%, very low-quality evidence). D-chiro-inositol (2 studies), rosiglitazone (1 study) or pioglitazone (1 study) versus placebo or no treatmentWe were unable to draw conclusions regarding other insulin-sensitising drugs as no studies reported primary outcomes. AUTHORS' CONCLUSIONS: Our updated review suggests that metformin alone may be beneficial over placebo for live birth, although the evidence quality was low. When metformin was compared with clomiphene citrate, data for live birth were inconclusive, and our findings were limited by lack of evidence. Results differed by body mass index (BMI), emphasising the importance of stratifying results by BMI. An improvement in clinical pregnancy and ovulation suggests that clomiphene citrate remains preferable to metformin for ovulation induction in obese women with PCOS.An improved clinical pregnancy and ovulation rate with metformin and clomiphene citrate versus clomiphene citrate alone suggests that combined therapy may be useful although we do not know whether this translates into increased live births. Women taking metformin alone or with combined therapy should be advised that there is no evidence of increased miscarriages, but gastrointestinal side effects are more likely.

Older people are majority users of health and social care services in the UK and internationally. Many older people who access these services have frailty, which is a state of vulnerability to adverse outcomes. The existing health care response to frailty is mainly secondary care-based and reactive to the acute health crises of falls, delirium and immobility. A more proactive, integrated, person-centred and community-based response to frailty is required. The British Geriatrics Society Fit for Frailty guideline is consensus best practice guidance for the management of frailty in community and outpatient settings. RECOGNITION OF FRAILTY: The BGS recommends that all encounters between health and social care staff and older people in community and outpatient settings should include an assessment for frailty. A gait speed <0.8m/s; a timed-up-and-go test >10s; and a score of ≥3 on the PRISMA 7 questionnaire can indicate frailty. The common clinical presentations of frailty (falls, delirium, sudden immobility) can also be used to indicate the possible presence of frailty. MANAGEMENT OF FRAILTY: The BGS recommends an holistic medical review based on the principles of comprehensive geriatric assessment (CGA) for all older people identified with frailty. This will: diagnose medical illnesses to optimise treatment; apply evidence-based medication review checklists (e.g. STOPP/START criteria); include discussion with older people and carers to define the impact of illness; work with the older person to create an individualised care and support plan. SCREENING FOR FRAILTY: The BGS does not recommend population screening for frailty using currently available instruments.

BACKGROUND: Few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT). METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY)control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130. FINDINGS: Between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44-61) in the younger age group and 76 years (73-78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41-59) in the younger age group and 78 years (75-82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5-2·3) in the half VLA group to 32·3 (24·8-42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7-1·6) for ChAd to 3·6 (2·4-5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0-1·5) in the half VLA group to 11·5 (9·4-14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7-1·6) for half VLA to 4·7 (3·1-7·1) for m1273. The results were similar between those aged 30-69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30-69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273. INTERPRETATION: All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination. FUNDING: UK Vaccine Taskforce and National Institute for Health Research.

OBJECTIVE: After randomizing 100 failed back surgery syndrome patients to receive spinal cord stimulation (SCS) plus conventional medical management (CMM) or CMM alone, the results of the 6-month Prospective Randomized Controlled Multicenter Trial of the Effectiveness of Spinal Cord Stimulation (i.e., PROCESS) showed that SCS offered superior pain relief, health-related quality of life, and functional capacity. Because the rate of crossover favoring SCS beyond 6 months would bias a long-term randomized group comparison, we present all outcomes in patients who continued SCS from randomization to 24 months and, for illustrative purposes, the primary outcome (>50% leg pain relief) per randomization and final treatment. METHODS: Patients provided data on pain, quality of life, function, pain medication use, treatment satisfaction, and employment status. Investigators documented adverse events. Data analysis included inferential comparisons and multivariate regression analyses. RESULTS: The 42 patients continuing SCS (of 52 randomized to SCS) reported significantly improved leg pain relief (P < 0.0001), quality of life (P <or= 0.01), and functional capacity (P = 0.0002); and 13 patients (31%) required a device-related surgical revision. At 24 months, of 46 of 52 patients randomized to SCS and 41 of 48 randomized to CMM who were available, the primary outcome was achieved by 17 (37%) randomized to SCS versus 1 (2%) to CMM (P = 0.003) and by 34 (47%) of 72 patients who received SCS as final treatment versus 1 (7%) of 15 for CMM (P = 0.02). CONCLUSION: At 24 months of SCS treatment, selected failed back surgery syndrome patients reported sustained pain relief, clinically important improvements in functional capacity and health-related quality of life, and satisfaction with treatment.

BACKGROUND: Delirium is a common mental disorder, which is distressing and has serious adverse outcomes in hospitalised patients. Prevention of delirium is desirable from the perspective of patients and carers, and healthcare providers. It is currently unclear, however, whether interventions for preventing delirium are effective. OBJECTIVES: To assess the effectiveness of interventions for preventing delirium in hospitalised non-Intensive Care Unit (ICU) patients. SEARCH METHODS: We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized Register on 4 December 2015 for all randomised studies on preventing delirium. We also searched MEDLINE (Ovid SP), EMBASE (Ovid SP), PsycINFO (Ovid SP), Central (The Cochrane Library), CINAHL (EBSCOhost), LILACS (BIREME), Web of Science core collection (ISI Web of Science), ClinicalTrials.gov and the WHO meta register of trials, ICTRP. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of single and multi- component non-pharmacological and pharmacological interventions for preventing delirium in hospitalised non-ICU patients. DATA COLLECTION AND ANALYSIS: Two review authors examined titles and abstracts of citations identified by the search for eligibility and extracted data independently, with any disagreements settled by consensus. The primary outcome was incidence of delirium; secondary outcomes included duration and severity of delirium, institutional care at discharge, quality of life and healthcare costs. We used risk ratios (RRs) as measures of treatment effect for dichotomous outcomes; and between group mean differences and standard deviations for continuous outcomes. MAIN RESULTS: We included 39 trials that recruited 16,082 participants, assessing 22 different interventions or comparisons. Fourteen trials were placebo-controlled, 15 evaluated a delirium prevention intervention against usual care, and 10 compared two different interventions. Thirty-two studies were conducted in patients undergoing surgery, the majority in orthopaedic settings. Seven studies were conducted in general medical or geriatric medicine settings.We found multi-component interventions reduced the incidence of delirium compared to usual care (RR 0.69, 95% CI 0.59 to 0.81; seven studies; 1950 participants; moderate-quality evidence). Effect sizes were similar in medical (RR 0.63, 95% CI 0.43 to 0.92; four studies; 1365 participants) and surgical settings (RR 0.71, 95% CI 0.59 to 0.85; three studies; 585 participants). In the subgroup of patients with pre-existing dementia, the effect of multi-component interventions remains uncertain (RR 0.90, 95% CI 0.59 to 1.36; one study, 50 participants; low-quality evidence).There is no clear evidence that cholinesterase inhibitors are effective in preventing delirium compared to placebo (RR 0.68, 95% CI, 0.17 to 2.62; two studies, 113 participants; very low-quality evidence).Three trials provide no clear evidence of an effect of antipsychotic medications as a group on the incidence of delirium (RR 0.73, 95% CI, 0.33 to 1.59; 916 participants; very low-quality evidence). In a pre-planned subgroup analysis there was no evidence for effectiveness of a typical antipsychotic (haloperidol) (RR 1.05, 95% CI 0.69 to 1.60; two studies; 516 participants, low-quality evidence). However, delirium incidence was lower (RR 0.36, 95% CI 0.24 to 0.52; one study; 400 participants, moderate-quality evidence) for patients treated with an atypical antipsychotic (olanzapine) compared to placebo (moderate-quality evidence).There is no clear evidence that melatonin or melatonin agonists reduce delirium incidence compared to placebo (RR 0.41, 95% CI 0.09 to 1.89; three studies, 529 participants; low-quality evidence).There is moderate-quality evidence that Bispectral Index (BIS)-guided anaesthesia reduces the incidence of delirium compared to BIS-blinded anaesthesia or clinical judgement (RR 0.71, 95% CI 0.60 to 0.85; two studies; 2057 participants).It is not possible to generate robust evidence statements for a range of additional pharmacological and anaesthetic interventions due to small numbers of trials, of variable methodological quality. AUTHORS' CONCLUSIONS: There is strong evidence supporting multi-component interventions to prevent delirium in hospitalised patients. There is no clear evidence that cholinesterase inhibitors, antipsychotic medication or melatonin reduce the incidence of delirium. Using the Bispectral Index to monitor and control depth of anaesthesia reduces the incidence of postoperative delirium. The role of drugs and other anaesthetic techniques to prevent delirium remains uncertain.

Aicardi-Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi-Goutières syndrome-related genes. Our findings also make it clear that a window of therapeutic opportunity exists relevant to the majority of affected patients and indicate that the assessment of type I interferon activity might serve as a useful biomarker in future clinical trials.

OBJECTIVE: To estimate the prevalence of wounds managed by the UK's National Health Service (NHS) in 2012/2013 and the annual levels of healthcare resource use attributable to their management and corresponding costs. METHODS: This was a retrospective cohort analysis of the records of patients in The Health Improvement Network (THIN) Database. Records of 1000 adult patients who had a wound in 2012/2013 (cases) were randomly selected and matched with 1000 patients with no history of a wound (controls). Patients' characteristics, wound-related health outcomes and all healthcare resource use were quantified and the total NHS cost of patient management was estimated at 2013/2014 prices. RESULTS: Patients' mean age was 69.0 years and 45% were male. 76% of patients presented with a new wound in the study year and 61% of wounds healed during the study year. Nutritional deficiency (OR 0.53; p<0.001) and diabetes (OR 0.65; p<0.001) were independent risk factors for non-healing. There were an estimated 2.2 million wounds managed by the NHS in 2012/2013. Annual levels of resource use attributable to managing these wounds and associated comorbidities included 18.6 million practice nurse visits, 10.9 million community nurse visits, 7.7 million GP visits and 3.4 million hospital outpatient visits. The annual NHS cost of managing these wounds and associated comorbidities was £5.3 billion. This was reduced to between £5.1 and £4.5 billion after adjusting for comorbidities. CONCLUSIONS: Real world evidence highlights wound management is predominantly a nurse-led discipline. Approximately 30% of wounds lacked a differential diagnosis, indicative of practical difficulties experienced by non-specialist clinicians. Wounds impose a substantial health economic burden on the UK's NHS, comparable to that of managing obesity (£5.0 billion). Clinical and economic benefits could accrue from improved systems of care and an increased awareness of the impact that wounds impose on patients and the NHS.

BACKGROUND: Various approaches to physical rehabilitation may be used after stroke, and considerable controversy and debate surround the effectiveness of relative approaches. Some physiotherapists base their treatments on a single approach; others use a mixture of components from several different approaches. OBJECTIVES: To determine whether physical rehabilitation approaches are effective in recovery of function and mobility in people with stroke, and to assess if any one physical rehabilitation approach is more effective than any other approach.For the previous versions of this review, the objective was to explore the effect of 'physiotherapy treatment approaches' based on historical classifications of orthopaedic, neurophysiological or motor learning principles, or on a mixture of these treatment principles. For this update of the review, the objective was to explore the effects of approaches that incorporate individual treatment components, categorised as functional task training, musculoskeletal intervention (active), musculoskeletal intervention (passive), neurophysiological intervention, cardiopulmonary intervention, assistive device or modality.In addition, we sought to explore the impact of time after stroke, geographical location of the study, dose of the intervention, provider of the intervention and treatment components included within an intervention. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched December 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 12, 2012), MEDLINE (1966 to December 2012), EMBASE (1980 to December 2012), AMED (1985 to December 2012) and CINAHL (1982 to December 2012). We searched reference lists and contacted experts and researchers who have an interest in stroke rehabilitation. SELECTION CRITERIA: Randomised controlled trials (RCTs) of physical rehabilitation approaches aimed at promoting the recovery of function or mobility in adult participants with a clinical diagnosis of stroke. Outcomes included measures of independence in activities of daily living (ADL), motor function, balance, gait velocity and length of stay. We included trials comparing physical rehabilitation approaches versus no treatment, usual care or attention control and those comparing different physical rehabilitation approaches. DATA COLLECTION AND ANALYSIS: Two review authors independently categorised identified trials according to the selection criteria, documented their methodological quality and extracted the data. MAIN RESULTS: We included a total of 96 studies (10,401 participants) in this review. More than half of the studies (50/96) were carried out in China. Generally the studies were heterogeneous, and many were poorly reported.Physical rehabilitation was found to have a beneficial effect, as compared with no treatment, on functional recovery after stroke (27 studies, 3423 participants; standardised mean difference (SMD) 0.78, 95% confidence interval (CI) 0.58 to 0.97, for Independence in ADL scales), and this effect was noted to persist beyond the length of the intervention period (nine studies, 540 participants; SMD 0.58, 95% CI 0.11 to 1.04). Subgroup analysis revealed a significant difference based on dose of intervention (P value < 0.0001, for independence in ADL), indicating that a dose of 30 to 60 minutes per day delivered five to seven days per week is effective. This evidence principally arises from studies carried out in China. Subgroup analyses also suggest significant benefit associated with a shorter time since stroke (P value 0.003, for independence in ADL).We found physical rehabilitation to be more effective than usual care or attention control in improving motor function (12 studies, 887 participants; SMD 0.37, 95% CI 0.20 to 0.55), balance (five studies, 246 participants; SMD 0.31, 95% CI 0.05 to 0.56) and gait velocity (14 studies, 1126 participants; SMD 0.46, 95% CI 0.32 to 0.60). Subgroup analysis demonstrated a significant difference based on dose of intervention (P value 0.02 for motor function), indicating that a dose of 30 to 60 minutes delivered five to seven days a week provides significant benefit. Subgroup analyses also suggest significant benefit associated with a shorter time since stroke (P value 0.05, for independence in ADL).No one physical rehabilitation approach was more (or less) effective than any other approach in improving independence in ADL (eight studies, 491 participants; test for subgroup differences: P value 0.71) or motor function (nine studies, 546 participants; test for subgroup differences: P value 0.41). These findings are supported by subgroup analyses carried out for comparisons of intervention versus no treatment or usual care, which identified no significant effects of different treatment components or categories of interventions. AUTHORS' CONCLUSIONS: Physical rehabilitation, comprising a selection of components from different approaches, is effective for recovery of function and mobility after stroke. Evidence related to dose of physical therapy is limited by substantial heterogeneity and does not support robust conclusions. No one approach to physical rehabilitation is any more (or less) effective in promoting recovery of function and mobility after stroke. Therefore, evidence indicates that physical rehabilitation should not be limited to compartmentalised, named approaches, but rather should comprise clearly defined, well-described, evidenced-based physical treatments, regardless of historical or philosophical origin.

The frequency of, and risk factors for, long COVID are unclear among community-based individuals with a history of COVID-19. To elucidate the burden and possible causes of long COVID in the community, we coordinated analyses of survey data from 6907 individuals with self-reported COVID-19 from 10 UK longitudinal study (LS) samples and 1.1 million individuals with COVID-19 diagnostic codes in electronic healthcare records (EHR) collected by spring 2021. Proportions of presumed COVID-19 cases in LS reporting any symptoms for 12+ weeks ranged from 7.8% and 17% (with 1.2 to 4.8% reporting debilitating symptoms). Increasing age, female sex, white ethnicity, poor pre-pandemic general and mental health, overweight/obesity, and asthma were associated with prolonged symptoms in both LS and EHR data, but findings for other factors, such as cardio-metabolic parameters, were inconclusive.

BACKGROUND: delirium is a common clinical problem and is associated with adverse health outcomes. Many medications have been associated with the development of delirium, but the strength of the associations is uncertain and it is unclear which medications should be avoided in people at risk of delirium. METHODS: we conducted a systematic review to identify prospective studies that investigated the association between medications and risk of delirium. A sensitivity analysis was performed to construct an evidence hierarchy for the risk of delirium with individual agents. RESULTS: a total of 18,767 studies were identified by the search strategy. Fourteen studies met the inclusion criteria. Delirium risk appears to be increased with opioids (odds ratio [OR] 2.5, 95% CI 1.2-5.2), benzodiazepines (3.0, 1.3-6.8), dihydropyridines (2.4, 1.0-5.8) and possibly antihistamines (1.8, 0.7-4.5). There appears to be no increased risk with neuroleptics (0.9, 0.6-1.3) or digoxin (0.5, 0.3-0.9). There is uncertainty regarding H(2) antagonists, tricyclic antidepressants, antiparkinson medications, steroids, non-steroidal anti-inflammatory drugs and antimuscarinics. CONCLUSION: for people at risk of delirium, avoid new prescriptions of benzodiazepines or consider reducing or stopping these medications where possible. Opioids should be prescribed with caution in people at risk of delirium, but this should be tempered by the observation that untreated severe pain can itself trigger delirium. Caution is also required when prescribing dihydropyridines and antihistamine H1 antagonists for people at risk of delirium and considered individual patient assessment is advocated.

Objective To evaluate the prevalence of wounds managed by the UK’s National Health Service (NHS) in 2017/2018 and associated health outcomes, resource use and costs. Design Retrospective cohort analysis of the electronic records of patients from The Health Improvement Network (THIN) database. Setting Primary and secondary care sectors in the UK. Participants Randomly selected cohort of 3000 patients from the THIN database who had a wound in 2017/2018. Primary and secondary outcome measures Patients’ characteristics, wound-related health outcomes, healthcare resource use and total NHS cost of patient management. Results There were an estimated 3.8 million patients with a wound managed by the NHS in 2017/2018, of which 70% healed in the study year; 89% and 49% of acute and chronic wounds healed, respectively. An estimated 59% of chronic wounds healed if there was no evidence of infection compared with 45% if there was a definite or suspected infection. Healing rate of acute wounds was unaffected by the presence of infection. Smoking status appeared to only affect the healing rate of chronic wounds. Annual levels of resource use attributable to wound management included 54.4 million district/community nurse visits, 53.6 million healthcare assistant visits and 28.1 million practice nurse visits. The annual NHS cost of wound management was £8.3 billion, of which £2.7 billion and £5.6 billion were associated with managing healed and unhealed wounds, respectively. Eighty-one per cent of the total annual NHS cost was incurred in the community. Conclusion The annual prevalence of wounds increased by 71% between 2012/2013 and 2017/2018. There was a substantial increase in resource use over this period and patient management cost increased by 48% in real terms. There needs to be a structural change within the NHS in order to manage the increasing demand for wound care and improve patient outcomes.

Few ill health situations are more degrading to people of any age than loss of reasoning, faculties, and personhood. These are the unpleasant consequences of delirium—a common condition affecting ill older people, particularly those with some degree of dementia. It is characterised by recent onset of fluctuating inattention and confusion, linked to one or more triggering factors. #### SUMMARY POINTS Delirium is a major burden to healthcare services and has been largely ignored by health service planners and practitioners.1 Moreover, healthcare systems and services often unintentionally stimulate or substantially aggravate the development of delirium in older people.2 This might be understandable if delirium was unavoidable or untreatable, but the existing evidence base for delirium is sufficiently robust for prevention or attenuation of the condition to be a realistic proposition. There is a pressing need to take this action because the outcomes for delirium are poor: it contributes to substantial morbidity and mortality, causes considerable distress to patients and families, and is expensive—an estimated additional $2500 (£1275; €1875) per patient (a $6.9bn annual expenditure for Medicare in 2004).3 We searched Medline and the Cochrane Library from 1996 to 2006. We drew additional material from our personal libraries of delirium references, focusing particularly on systematic reviews. Delirium is an important problem for all clinical services providing care for older people, particularly emergency departments; general medical, elderly care, surgical, and …

BACKGROUND: Research shows that stroke patients and their families are dissatisfied with the information provided and have a poor understanding of stroke and associated issues. OBJECTIVES: To assess the effectiveness of information provision strategies in improving the outcome for stroke patients or their identified caregivers, or both. SEARCH METHODS: For this update we searched the Cochrane Stroke Group Trials Register (June 2012), the Cochrane Central Register of Controlled trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR), the Database of Abstracts of Reviews of Effects (DARE), the NHS Economic Evaluation Database (EED), and the Health Technology Assessment (HTA) Database (The Cochrane Library June, 2012), MEDLINE (1966 to June 2012), EMBASE (1980 to June 2012), CINAHL (1982 to June 2012) and PsycINFO (1974 to June 2012). We also searched ongoing trials registers, scanned bibliographies of relevant articles and books and contacted researchers. SELECTION CRITERIA: Randomised trials involving patients or carers of patients with a clinical diagnosis of stroke or transient ischaemic attack (TIA) where an information intervention was compared with standard care, or where information and another therapy were compared with the other therapy alone. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and methodological quality and extracted data. Primary outcomes were knowledge about stroke and stroke services, and impact on mood. MAIN RESULTS: We have added four new trials to this update. This review now includes 21 trials involving 2289 patient and 1290 carer participants. Nine trials evaluated a passive and 12 trials an active information intervention. Meta-analyses showed a significant effect in favour of the intervention on patient knowledge (standardised mean difference (SMD) 0.29, 95% confidence interval (CI) 0.12 to 0.46, P < 0.001), carer knowledge (SMD 0.74, 95% CI 0.06 to 1.43, P = 0.03), one aspect of patient satisfaction (odds ratio (OR) 2.07, 95% CI 1.33 to 3.23, P = 0.001), and patient depression scores (mean difference (MD) -0.52, 95% CI -0.93 to -0.10, P = 0.01). There was no significant effect (P > 0.05) on number of cases of anxiety or depression in patients, carer mood or satisfaction, or death. Qualitative analyses found no strong evidence of an effect on other outcomes. Post-hoc subgroup analyses showed that active information had a significantly greater effect than passive information on patient mood but not on other outcomes. AUTHORS' CONCLUSIONS: There is evidence that information improves patient and carer knowledge of stroke, aspects of patient satisfaction, and reduces patient depression scores. However, the reduction in depression scores was small and may not be clinically significant. Although the best way to provide information is still unclear there is some evidence that strategies that actively involve patients and carers and include planned follow-up for clarification and reinforcement have a greater effect on patient mood.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are common diseases of the airways and lungs that have a major impact on the health of the population. The mainstay of treatment is by inhalation of medication to the site of the disease process. This can be achieved by a number of different device types, which have wide variations in costs to the health service. A number of different inhalation devices are available. The pressurised metered-dose inhaler (pMDI) is the most commonly used and cheapest device, which may also be used in conjunction with a spacer device. Newer chlorofluorocarbons (CFC)-free inhaler devices using hydrofluoroalkanes (HFAs) have also been developed. The drug is dissolved or suspended in the propellant under pressure. When activated, a valve system releases a metered volume of drug and propellant. Other devices include breath-actuated pMDIs (BA-pMDI), such as Autohaler and Easi-Breathe. They incorporate a mechanism activated during inhalation that triggers the metered-dose inhaler. Dry powder inhalers (DPI), such as Turbohaler, Diskhaler, Accuhaler and Rotahaler, are activated by inspiration by the patient. The powdered drug is dispersed into particles by the inspiration. With nebulisers oxygen, compressed air, or ultrasonic power is used to break up solutions or suspensions of medication into droplets for inhalation. The aerosol is administered by mask or by a mouthpiece. There has been no previous systematic review of the evidence of clinical effectiveness and cost-effectiveness of these different inhaler devices. OBJECTIVES: To review systematically the clinical effectiveness and cost-effectiveness of inhaler devices in asthma and COPD. METHODS: The different aspects of inhaler devices were separated into the most clinically relevant comparisons. Methods involved systematic searching of electronic databases and bibliographies for randomised controlled trials (RCTs) and systematic reviews. Pharmaceutical companies and experts in the field were contacted for further information. Trials that met the inclusion criteria were appraised and data extraction was under-taken by one reviewer and checked by a second reviewer, with any discrepancies being resolved through agreement. RESULTS--IN VITRO CHARACTERISTICS VERSUS IN VIVO TESTING AND CLINICAL RESPONSE: There is evidence that when comparative testing is performed on inhaler devices using the same methods, there is some correlation between particle size measurements and clinical response. However, the measurements are dependent upon the methods used, and a single measure of a device in isolation is of limited value. Also, there is little data on comparing devices of different types. There is currently insufficient data to verify the ability of in vitro assessments to predict inhaler performance in vivo. RESULTS--EFFECTIVENESS OF METERED-DOSE INHALERS FOR THE DELIVERY OF CORTICOSTEROIDS IN ASTHMA: The review of three trials in children and 21 trials in adults demonstrated no evidence to suggest clinical benefits of any other inhaler device over a pMDI in corticosteroid delivery. RESULTS--EFFECTIVENESS OF METERED-DOSE INHALERS FOR THE DELIVERY OF BETA-AGONISTS IN STABLE ASTHMA: In children, 11 studies were reviewed, of which seven compared the Turbohaler with the pMDI. One study found a significant treatment difference in peak expiratory flow rate, although there were differences in the patients' baseline characteristics. In adults, a review of 70 studies found no demonstrable difference in the clinical bronchodilator effect of short-acting b2-agonists delivered by the standard pMDI compared with that produced by any other DPI, HFA-pMDI or the Autohaler device. The finding that HFA-pMDIs may reduce treatment failure and oral steroid requirement in beta-agonist delivery needs further confirmatory research in adequately randomised clinical trials. RESULTS--EFFECTIVENESS OF NEBULISERS VERSUS METERED-DOSE INHALERS FOR THE DELIVERY OF BRONCHODILATORS IN STABLE ASTHMA: In children, three included trials compared different devices with a nebuliser and demonstrated no evidence of clinical superiority of nebulisers over inhaler devices in bronchodilator delivery. A total of 23 studies in adults found no equivalence for the main pulmonary outcomes and no evidence of difference in other outcomes. RESULTS--EFFECTIVENESS OF METERED-DOSE INHALERS FOR THE DELIVERY OF BETA-AGONISTS IN COPD: Only two studies were included in this review. No evidence of clinical difference was found in beta-agonist delivery. RESULTS--EFFECTIVENESS OF NEBULISERS VERSUS METERED-DOSE INHALERS FOR THE DELIVERY OF BRONCHODILATORS IN COPD: Evidence from 14 trials demonstrated equivalence for the main outcomes of pulmonary function. For other outcomes there was no evidence of treatment difference in bronchodilator delivery. RESULTS--PATIENTS' ABILITY TO USE METERED-DOSE INHALERS: Differences among studies and the heterogeneity of the results make it difficult to draw conclusions about inhaler technique differences between device types. The review of technique after teaching the correct technique suggests that there is no difference in patients' ability to use DPI or pMDIs. RESULTS--ECONOMIC ANALYSIS: The total number of NHS prescriptions for inhaler therapy for asthma in 1998 was over 31 million, with a net ingredient cost in excess of 392 million GB pounds. This economic assessment uses decision analysis to estimate the relative cost-effectiveness of inhaler devices for the delivery of bronchodilator and corticosteroid inhaled therapy. Overall, there were no differences in patient outcomes among the devices. On the assumption that the devices were clinically equivalent, pMDIs were the most cost-effective devices for asthma treatment. CONCLUSIONS: This systematic review examined the evidence from clinical trials evaluating the clinical effectiveness of different inhaler devices in the delivery of inhaled corticosteroids and beta2-bronchodilators for patients with asthma and COPD. The evidence from the published clinical literature demonstrates no difference in clinical effectiveness between nebulisers and alternative inhaler devices compared to standard pMDI with or without a spacer device. The cost-effectiveness evidence therefore favours pMDIs (or the cheapest inhaler device) as first-line treatment in all patients with stable asthma unless other specific reasons are identified. Patients can use pMDIs as effectively as other inhaler devices as long as the correct inhalation technique is taught. CONCLUSIONS--RECOMMENDATIONS FOR RESEARCH: Further clinical trials are required to demonstrate any differences in the clinical effectiveness and cost-effectiveness of inhaler devices and nebulisers compared with pMDIs. These should be of sufficient statistical power and methodological rigour to demonstrate any clinical benefit. Trials should be undertaken in community settings to ensure the generalisability of results. Outcome measures should be more patient-centred and report adverse effects more completely. Reporting of data from trials should be improved.