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Objective: To systematically review the conduct and reporting of formula trials., Design: Systematic review., Data Sources: Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from 1 January 2006 to 31 December 2020., Review Methods: Intervention trials comparing at least two formula products in children less than three years of age were included, but not trials of human breast milk or fortifiers of breast milk. Data were extracted in duplicate and primary outcome data were synthesised for meta-analysis with a random effects model weighted by the inverse variance method. Risk of bias was evaluated with Cochrane risk of bias version 2.0, and risk of undermining breastfeeding was evaluated according to published consensus guidance. Primary outcomes of the trials included in the systematic review were identified from clinical trial registries, protocols, or trial publications., Results: 22 201 titles were screened and 307 trials were identified that were published between 2006 and 2020, of which 73 (24%) trials in 13 197 children were prospectively registered. Another 111 unpublished but registered trials in 17 411 children were identified. Detailed analysis was undertaken for 125 trials (23 757 children) published since 2015. Seventeen (14%) of these recently published trials were conducted independently of formula companies, 26 (21%) were prospectively registered with a clear aim and primary outcome, and authors or sponsors shared prospective protocols for 11 (9%) trials. Risk of bias was low in five (4%) and high in 100 (80%) recently published trials, mainly because of inappropriate exclusions from analysis and selective reporting. For 68 recently published superiority trials, a pooled standardised mean difference of 0.51 (range -0.43 to 3.29) was calculated with an asymmetrical funnel plot (Egger's test P<0.001), which reduced to 0.19 after correction for asymmetry. Primary outcomes were reported by authors as favourable in 86 (69%) trials, and 115 (92%) abstract conclusions were favourable. One of 38 (3%) trials in partially breastfed infants reported adequate support for breastfeeding and 14 of 87 (16%) trials in non-breastfed infants confirmed the decision not to breastfeed was firmly established before enrolment in the trial., Conclusions: The results show that formula trials lack independence or transparency, and published outcomes are biased by selective reporting., Systematic Review Registration: PROSPERO 2018 CRD42018091928., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare support from Imperial Health Charity: RJB received personal fees from Cochrane, DBV Technologies, and Prota Therapeutics, and from expert witness work in cases of food anaphylaxis and class actions related to infant formula health claims, outside the submitted work, and received personal fees from Public Health England as a member of the UK Nutrition and Health Claims Committee and the Maternal and Child Nutrition Subgroup of the Scientific Advisory Committee on Nutrition. JL-B received fees from Danone Nutricia Research and the Food Standards Agency, outside of the submitted work. The University of Colorado receives remuneration for LB’s work as senior editor, Cochrane, which is outside the submitted work. The authors report no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine whether feeding infants with hydrolysed formula reduces their risk of allergic or autoimmune disease., Design: Systematic review and meta-analysis, as part of a series of systematic reviews commissioned by the UK Food Standards Agency to inform guidelines on infant feeding. Two authors selected studies by consensus, independently extracted data, and assessed the quality of included studies using the Cochrane risk of bias tool., Data Sources: Medline, Embase, Web of Science, CENTRAL, and LILACS searched between January 1946 and April 2015., Eligibility Criteria for Selecting Studies: Prospective intervention trials of hydrolysed cows' milk formula compared with another hydrolysed formula, human breast milk, or a standard cows' milk formula, which reported on allergic or autoimmune disease or allergic sensitisation., Results: 37 eligible intervention trials of hydrolysed formula were identified, including over 19,000 participants. There was evidence of conflict of interest and high or unclear risk of bias in most studies of allergic outcomes and evidence of publication bias for studies of eczema and wheeze. Overall there was no consistent evidence that partially or extensively hydrolysed formulas reduce risk of allergic or autoimmune outcomes in infants at high pre-existing risk of these outcomes. Odds ratios for eczema at age 0-4, compared with standard cows' milk formula, were 0.84 (95% confidence interval 0.67 to 1.07; I(2)=30%) for partially hydrolysed formula; 0.55 (0.28 to 1.09; I(2)=74%) for extensively hydrolysed casein based formula; and 1.12 (0.88 to 1.42; I(2)=0%) for extensively hydrolysed whey based formula. There was no evidence to support the health claim approved by the US Food and Drug Administration that a partially hydrolysed formula could reduce the risk of eczema nor the conclusion of the Cochrane review that hydrolysed formula could allergy to cows' milk., Conclusion: These findings do not support current guidelines that recommend the use of hydrolysed formula to prevent allergic disease in high risk infants., Review Registration: PROSPERO CRD42013004252., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: To assess the effects of treatments for non-metastatic invasive squamous cell carcinoma (SCC) of the skin using evidence from observational studies, given the paucity of evidence from randomised controlled trials., Design: Systematic review of observational studies., Data Sources: Medline, Embase, to December 2012., Review Methods: Observational studies of interventions for primary, non-metastatic, invasive, SCC of the skin that reported recurrence during follow-up, quality of life, initial response to treatment, adverse events, cosmetic appearance, or death from disease. Studies were excluded if data for primary cutaneous SCC was not separable from other data. Data were extracted independently by two reviewers. Meta-analysis was performed where appropriate using a random effects model to estimate the pooled proportion of an event with 95% confidence intervals., Results: 118 publications were included, covering seven treatment modalities. Pooled estimates of recurrence of SCCs were lowest after cryotherapy (0.8% (95% confidence interval 0.1% to 2%)) and curettage and electrodesiccation (1.7% (0.5% to 3.4%)), but most treated SCCs were small, low risk lesions. After Mohs micrographic surgery, the pooled estimate of local recurrence during variable follow-up periods from 10 studies was 3.0% (2.2% to 3.9%), which was non-significantly lower than the pooled average local recurrence of 5.4% (2.5% to 9.1%) after standard surgical excision (12 studies), and 6.4% (3.0% to 11.0%) after external radiotherapy (7 studies). After an apparently successful initial response of SCCs to photodynamic therapy, pooled average recurrence of 26.4% (12.3% to 43.7%; 8 studies) was significantly higher than other treatments. Evidence was limited for laser treatment (1 study) and for topical and systemic treatments (mostly single case reports or small non-comparative series with limited follow-up)., Conclusions: Many observational studies have looked at different treatment modalities for SCC, but the evidence base for the effectiveness of these interventions is poor. Comparison of outcomes after different treatments should be interpreted cautiously owing to biases inherent in the types of study included, and lack of direct comparisons to enable the estimation of relative treatment effect. Further evidence is needed to develop a prognostic model and stratify individuals at high risk of developing SCC, to improve the evidence base for this common cancer and to optimise clinical management., Protocol Registration: International Prospective Register of Systematic Reviews (PROSPERO) registration number CRD42011001450.

Objectives: To investigate the effectiveness of the systematic default provision of smoking cessation support to all adult smokers admitted to hospital, relative to usual care., Design: Open, cluster randomised controlled trial., Setting: Acute medical wards in one large teaching hospital in the United Kingdom., Participants: 264 patients randomised to intervention and 229 to usual care; primary outcome data were available at four weeks for 260 and 224 patients, respectively. All adult smokers and recent ex-smokers able to give informed consent were eligible for entry into the study., Interventions: The intervention comprised systematic smoking ascertainment and default provision of behavioural support and cessation pharmacotherapy for the duration of the hospital stay for all smokers and recent ex-smokers, with follow-up and referral to community services after discharge. Usual care comprised cessation support delivered at the initiative and discretion of clinical staff. All staff and patients were aware of group assignment., Main Outcome Measures: Smoking cessation at four weeks, validated by measuring exhaled carbon monoxide. Secondary outcomes were uptake of inpatient behavioural support, use of cessation pharmacotherapy, referral to and uptake of community support after discharge, and validated smoking cessation at six months. Participants lost to follow-up were assumed to have reverted to smoking., Results: All patients in the intervention group received at least brief advice to quit smoking, compared to 106 (46%) patients in the usual care group. Cessation at four weeks was achieved by 38% (n=98) of intervention patients and 17% (n=37) of usual care patients (adjusted odds ratio 2.10 (95% confidence interval 0.96 to 4.61), P=0.06, number of patients needed to treat 8). Uptake of inpatient behavioural support, use of pharmacotherapy, and referral to and uptake of community support after discharge were all substantially and statistically significantly higher in the intervention group than in the usual care group. Cessation at six months was achieved by 19% (n=47) of intervention and 9% (n=19) of usual care patients, although this difference was not significant (adjusted odds ratio 1.53 (95% confidence interval 0.60 to 3.91); P=0.37)., Conclusions: Substantial improvements in smoking cessation among smokers admitted to hospital can be achieved by systematic ascertainment and delivery of cessation support in secondary care., Trial Registration: International Standard Randomised Controlled Trial Number ISRCTN25441641.

Objective: To determine whether occupational therapy focused specifically on personal activities of daily living improves recovery for patients after stroke., Design: Systematic review and meta-analysis., Data Sources: The Cochrane stroke group trials register, the Cochrane central register of controlled trials, Medline, Embase, CINAHL, PsycLIT, AMED, Wilson Social Sciences Abstracts, Science Citation Index, Social Science Citation, Arts and Humanities Citation Index, Dissertations Abstracts register, Occupational Therapy Research Index, scanning reference lists, personal communication with authors, and hand searching., Review Methods: Trials were included if they evaluated the effect of occupational therapy focused on practice of personal activities of daily living or where performance in such activities was the target of the occupational therapy intervention in a stroke population. Original data were sought from trialists. Two reviewers independently reviewed each trial for methodological quality. Disagreements were resolved by consensus., Results: Nine randomised controlled trials including 1258 participants met the inclusion criteria. Occupational therapy delivered to patients after stroke and targeted towards personal activities of daily living increased performance scores (standardised mean difference 0.18, 95% confidence interval 0.04 to 0.32, P=0.01) and reduced the risk of poor outcome (death, deterioration or dependency in personal activities of daily living) (odds ratio 0.67, 95% confidence interval 0.51 to 0.87, P=0.003). For every 100 people who received occupational therapy focused on personal activities of daily living, 11 (95% confidence interval 7 to 30) would be spared a poor outcome., Conclusions: Occupational therapy focused on improving personal activities of daily living after stroke can improve performance and reduce the risk of deterioration in these abilities. Focused occupational therapy should be available to everyone who has had a stroke.