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Christos V Chalitsios,1,* Ralph K Akyea,2,* Hasidah Abdul-Hamid,2,3 Jo Leonardi-Bee,1,4 Johanes D Kanchau,5 Aisyah Kamal,5 Mohamed-Syarif Mohamed-Yassin,3 Noorhida Baharudin,3,5 Anis Safura Ramli,3,5 Nadeem Qureshi2 1Nottingham Centre for Epidemiology and Public Health, Lifespan and Population Health Unit, School of Medicine, University of Nottingham, Nottingham, UK; 2PRISM Research Group, Centre for Academic Primary Care, Lifespan and Population Health Unit, School of Medicine, University of Nottingham, Nottingham, UK; 3Department of Primary Care Medicine, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia; 4Centre for Evidence-Based Medicine, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK; 5Institute of Pathology, Laboratory and Forensic Medicine (I‑PPerForM), Universiti Teknologi MARA, Sungai Buloh, Selangor, Malaysia*These authors contributed equally to this workCorrespondence: Nadeem Qureshi, Centre for Academic Primary Care, School of Medicine, University of Nottingham, Nottingham, UK, Email Nadeem.Qureshi@nottingham.ac.uk

Background: Bisphosphonates are effective in preventing fragility fractures; however, high rates of adherence are needed to preserve clinical benefits. Objective: To investigate persistence and compliance to oral and intravenous bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate). Methods: Searches of 12 databases, unpublished sources, and trial registries were conducted, covering the period from 2000 to April 2021. Screening, data extraction, and risk of bias assessment (Cochrane Collaboration risk-of-bias tool 1.0 & ROBINS-I) were independently undertaken by two study authors. Randomised controlled trials (RCTs) and observational studies that used prescription claim databases or hospital medical records to examine patients' adherence were included. Network meta-analyses (NMA) embedded within a Bayesian framework were conducted, investigating users' likelihood in discontinuing bisphosphonate treatment. Where meta-analysis was not possible, data were synthesised using the vote-counting synthesis method. Results: Fifty-nine RCTs and 43 observational studies were identified, resulting in a total population of 2,656,659 participants. Data from 59 RCTs and 24 observational studies were used to populate NMAs. Zoledronate users were the least likely to discontinue their treatment HR = 0.73 (95%CrI: 0.61, 0.88). Higher rates of compliance were observed in those receiving intravenous treatments. The paucity of data and the heterogeneity in the reported medication possession ratio thresholds precluded a NMA of compliance data. Conclusions: Users of intravenously administered bisphosphonates were found to be the most adherent to treatment among bisphosphonates' users. Patterns of adherence will permit the more precise estimation of clinical and cost-effectiveness of bisphosphonates. Trial registration: PROSPERO 2020 CRD42020177166 [ABSTRACT FROM AUTHOR]

Summary: Background: Basal cell carcinoma (BCC) is the most common cancer affecting white‐skinned individuals, and the worldwide incidence is increasing. Although rarely fatal, BCC is associated with significant morbidity and costs. Objectives: To assess the effects of interventions for primary BCC in immunocompetent adults. Methods: We updated our searches of the following databases to November 2019: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and LILACS. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation method. We used standard methodological procedures expected by Cochrane. Results: We included 52 randomized controlled trials with 6990 participants (median age 65 years; range 20–95). Mean study duration was 13 months (range 6 weeks–10 years). Ninety‐two per cent (n = 48/52) of studies exclusively included histologically low‐risk BCC (nodular and superficial subtypes). The certainty of evidence was predominantly low or moderate for the outcomes of interest. Overall, surgical interventions have the lowest recurrence rates, and there may be slightly fewer recurrences with Mohs micrographic surgery over surgical excision for primary, facial BCC (high‐risk histological subtype or located in the 'H‐zone' or both) (low‐certainty evidence). Nonsurgical treatments, when used for low‐risk BCC, are less effective than surgical treatments, but recurrence rates are acceptable and cosmetic outcomes are probably superior. Conclusions: Surgical interventions have lower recurrence rates and remain the gold standard for high‐risk BCC. Of the nonsurgical treatments, topical imiquimod has the best evidence to support its efficacy for low‐risk BCC. Priorities for future research include agreement on core outcome measures and studies with longer follow‐up. What is already known about this topic? Basal cell carcinoma (BCC) is the most common cancer to affect white‐skinned individuals, and worldwide incidence is increasing.A 2007 Cochrane review concluded that there was very little good‐quality research on treatments for BCC and that surgical interventions and radiotherapy had the lowest recurrence rates. What does this study add? The body of evidence has now doubled to 52 trials, but most deal with low‐risk lesions.The quality of evidence remains generally low to moderate.Surgical interventions still have the lowest recurrence rates, and there may be slightly fewer recurrences with Mohs micrographic surgery over surgical excision for high‐risk facial primary BCC.Nonsurgical treatments are less effective than surgery, but recurrence rates are acceptable for low‐risk lesions and cosmetic outcomes are probably superior. Linked Comment: L.C.J. van Delft and N.W.J. Kelleners-Smeets. Br J Dermatol 2021; 185:475. [ABSTRACT FROM AUTHOR]

The aim of this editorial is to briefly discuss the use of multiplicity correction in different contexts and to state the multiplicity requirements for publication in the I BJD i . This multiplicity correction leads to an FWER close to the target overall type I error level when all tests are independent, but it is known to be overly conservative when the tested hypotheses are related, leading to an unnecessary loss of power (i.e. lower probability of finding true associations). Indeed, when multiple true null hypotheses are tested, the probability of rejecting at least one null hypothesis [referred to as the overall type I error rate or family-wise error rate (FWER)] increases with the number of tests. [Extracted from the article]

Background: The UK National Health Service provides Stop Smoking Services for pregnant women (SSSP) but there is a lack of evidence concerning how these are best organised. This study investigates influences on services' effectiveness and also on their propensity to engage pregnant smokers with support in stopping smoking.Methods: Survey data collected from 121/141 (86%) of SSSP were augmented with data from Hospital Episode Statistics and the 2011 UK National Census. 'Reach' or propensity to engage smokers with support was defined as the percentage of pregnant smokers setting a quit date with SSSP support, and 'Effectiveness' as the percentage of women who set a quit date who also reported abstinence at four weeks later. A bivariate (i.e. two outcome variable) response Markov Chain Monte Carlo model was used to identify service-level factors associated with the Reach and Effectiveness of SSSP.Results: Beta coefficients represent a percentage change in Reach and Effectiveness by the covariate. Providing the majority of one-to-one contacts in a clinic rather than at home increased both Reach (%) (β: 6.97, 95% CI: 3.34, 10.60) and Effectiveness (%) (β: 7.37, 95% CI: 3.03, 11.70). Reach of SSSP was also increased when the population served was more deprived (β for increase in Reach with a one unit increase in IMD score: 0.55, 95% CI: 0.25, 0.85), had a lower proportion of people with dependent children (β: -2.52, 95% CI: -3.82, -1.22), and a lower proportion of people in managerial or professional occupations (β: -0.31, 95% CI: -0.59, -0.03). The Effectiveness of SSSP was decreased in those areas that had a greater percentage of people >16 years with no educational qualifications (β: -0.51, 95% CI: -0.95, -0.07).Conclusions: To engage pregnant smokers and to encourage them to quit, it may be more efficient for SSSP support to be focussed around clinics, rather than women's homes. Reach of SSSP is inversely associated with disadvantage and efforts should be made to contact these women as they are less likely to achieve abstinence in the short and longer term. [ABSTRACT FROM AUTHOR]

Systematic reviews have become an increasingly popular tool to assess best evidence and have an established place at the top of the evidence pyramid, above individual randomized controlled trials (RCTs). Meta-analyses are useful as they provide estimates of effect from more than one study and therefore will have increased statistical power (through larger sample size) and have improved estimates of precision (through smaller standard errors), thus yielding narrower confidence intervals (CIs) for the effect estimate; therefore, the more certain we are that the effect estimate reflects the true effect size. It is important to remember that subgroup and sensitivity analyses are observational associations, not causal, as any observed effect could be due to confounding, bias or chance. [Extracted from the article]

'Interventions for basal cell carcinoma: abridged Cochrane systematic review and GRADE assessments': reply from the authors References 1 Mazzoni D, Muir J. Response to 'Interventions for basal cell carcinoma: abridged Cochrane systematic review and GRADE assessments'. In our Cochrane review's conclusions, we highlighted the paucity of evidence on C&C, and given how commonly used this technique is, we stressed the need for further randomized controlled trials with long-term follow-up assessing this treatment modality. [Extracted from the article]

Background Basal cell carcinoma ( BCC) is one of the most common types of nonmelanoma skin cancer affecting the white population; however, little is known about how the incidence varies across the U.K. Objectives To determine the variation in BCC throughout the U.K. Methods Data from 2004 to 2010 were obtained from The Health Improvement Network database. European and world age-standardized incidence rates ( EASRs and WASRs, respectively) were obtained for country-level estimates and levels of socioeconomic deprivation, while strategic health-authority-level estimates were directly age and sex standardized to the U.K. standard population. Incidence-rate ratios were estimated using multivariable Poisson regression models. Results The overall EASR and WASR of BCC in the U.K. were 98·6 per 100 000 person-years and 66·9 per 100 000 person-years, respectively. Regional-level incidence rates indicated a significant geographical variation in the distribution of BCC, which was more pronounced in the southern parts of the country. The South East Coast had the highest BCC rate followed by South Central, Wales and the South West. Incidence rates were substantially higher in the least deprived groups and we observed a trend of decreasing incidence with increasing levels of deprivation ( P < 0·001). Finally, in terms of age groups, the largest annual increase was observed among those aged 30-49 years. Conclusions Basal cell carcinoma is an increasing health problem in the U.K.; the southern regions of the U.K. and those in the least deprived groups had a higher incidence of BCC. Our findings indicate an increased incidence of BCC for younger age groups below 49 years. [ABSTRACT FROM AUTHOR]

Background: The impact of neuraminidase inhibitor (NAI) treatment on clinical outcomes of public health importance during the 2009-2010 pandemic has not been firmly established.Methods: We conducted a systematic review and meta-analysis, searching 11 databases (2009 through April 2012) for relevant studies. We used standard methods conforming to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random effects models.Results: Regarding mortality we observed a nonsignificant reduction associated with NAI treatment (at any time) versus none (OR, 0.72 [95% CI, .51-1.01]). However we observed significant reductions for early treatment (≤48 hours after symptom onset) versus late (OR, 0.38 [95% CI, .27-.53]) and for early treatment versus none (OR, 0.35 [95% CI, .18-.71]). NAI treatment (at any time) versus none was associated with an elevated risk of severe outcome (OR, 1.76 [95% CI, 1.22-2.54]), but early versus late treatment reduced the likelihood (OR, 0.41 [95% CI, .30-.56]).Conclusions: During the 2009-2010 influenza A(H1N1) pandemic, early initiation of NAI treatment reduced the likelihood of severe outcomes compared with late or no treatment.Prospero Registration: CRD42011001273. [ABSTRACT FROM AUTHOR]

Linked Article: Jabbar‐Lopez et al. Br J Dermatol 2020; 183:285–293. [ABSTRACT FROM AUTHOR]

RATIONALE: Epidemiologic studies suggest that intestinal parasite infections may protect against asthma. OBJECTIVES: A systematic review and meta-analysis of epidemiologic studies to determine whether total or species-specific current parasite infection is associated with a reduced risk of asthma or wheeze. METHODS: We searched MEDLINE, EMBASE, and CINAHL (up to January 2006); reviews; and reference lists from publications, with no language restrictions. We included studies that reported asthma or wheeze as an outcome measure and ascertained parasite infection by fecal examination. We estimated pooled odds ratios (OR) and 95% confidence intervals (CI) using data extracted from published papers, or where available, original data provided by authors, using random effect models. MEASUREMENTS AND MAIN RESULTS: Thirty-three studies met the inclusion criteria. Infection with any parasite was associated with a small, nonsignificant increase in asthma risk (OR, 1.24; 95% CI, 0.98-1.57; 29 studies). In species-specific analysis, Ascaris lumbricoides was associated with significantly increased odds of asthma (OR, 1.34; 95% CI, 1.05-1.71; 20 studies), while hookworm infection was associated with a significantly strong reduction (OR, 0.50; 95% CI, 0.28-0.90; 9 studies) that was directly and significantly related to infection intensity (p < 0.001; OR for highest tertile of infection, 0.34; 95% CI, 0.19-0.62). Other species had no significant effects on asthma. Infection effects on wheeze were derived from smaller numbers, but revealed a broadly similar pattern of results. CONCLUSIONS: Parasite infections do not in general protect against asthma, but infection with hookworm may reduce the risk of this disease. [ABSTRACT FROM AUTHOR]

Objective: Glycosylated hemoglobin (GHb) is a well-validated measure of control in diabetics but fasting glucose levels account for only a portion of the variance in non-diabetics. Stress has been suggested as a factor driving socio-economic inequalities in health and GHb appears to be elevated in stressed populations. This project examined the relationship between GHb levels and measures of socio-economic status (SES) in non-diabetics. Methods: Data were used from 1828 individuals in the National Health and Nutrition Examination Survey (NHANES) 1999–2000 dataset with fasting glucose samples and GHb levels (HbA1c) <7.5 per cent. The effect of adding individual measures of SES to the models after controlling for explanatory factors was assessed. Results: Associations were found, in non-diabetics, between HbA1c levels and measures of SES after controlling for fasting glucose level, age and weekly alcohol consumption in both men and women. For men, serum insulin also contributed to the models. Conclusion: SES was found to have graded relationships with HbA1c and relatively small or non-existent associations with other metabolic syndrome factors. HbA1c levels were significantly associated with three measures of social status in women and four measures in men. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a study on the effectiveness of dipyridamole in reducing recurrent stroke. 5 RCTs were included in the intention to treat meta-analysis of individual patient data using a logistic regression model with random effects for trial and fixed effects for treatment assignment. Risk of recurrent all stroke and the risk of non-fatal stroke were lower in the dipyridamole group than in the control group. Researchers concluded that in patients with a history of ischaemic cerebrovascular disease, dipyridamole given with or without aspirin reduces the risk of recurrent stroke.

Background: Neuraminidase inhibitors (NAIs) were widely deployed during the 2009 A(H1N1) pandemic. While evidence exists to support their effectiveness in reducing mortality in hospitalised patients, the impact of outpatient or community-based treatment on hospital admission has not been established. Our aim was to investigate the association between outpatient or community-based NAI treatment and admission to hospital in patients with A(H1N1)pdm09 virus infection. Methods & Materials: We performed an Individual Participant Data (IPD) meta-analysis on a pooled dataset of 6,030 patients from nine different countries. 'Admission to hospital' was the main outcome and 'NAI treatment initiated in the community or as an outpatient' was the main exposure variable. We estimated Odds Ratios (OR) and 95% Confidence Intervals (95% CI) using generalised linear mixed modelling to account for clustering within each contributing study centre; and we adjusted for pre-admission antibiotics and NAI treatment propensity in the final model. To account for relatively frequent exposure to NAI treatment and an overall high likelihood of hospitalisation, we also estimated Risk Ratios (RR) using a random effects probit model. Results: Of the 6,030 patients included in the pooled analysis, 5,738 (95.16%) had laboratory confirmed influenza A(H1N1)pdm09, and the remainder were clinically diagnosed with 'pandemic influenza'. A total of 1,541 patients (25.56%) received outpatient or community-based NAI treatment and 4,250 (70.48%) hospitalisations occurred, indicating a population at overall high-risk of influenza-related hospitalisation. After adjustment for pre-admission antibiotics and NAI treatment propensity, out-patient or community-based NAI treatment was associated with a decreased odds of hospital admission (OR: 0.33, 95% CI: 0.28 to 0.39) compared to no NAI treatment. From our random effects probit model, we obtained a corresponding adjusted RR of 0.52 (0.48 to 0.57). Conclusion: In a population with confirmed or suspected A(H1N1)pdm09, and at high risk of hospital admission, outpatient or community-based NAI treatment substantially reduced the likelihood of requiring hospital admission. [ABSTRACT FROM AUTHOR]

B Introduction: b Familial hypercholesterolaemia (FH) is a known major cause of premature heart disease. Incident rates of coronary heart disease (CHD), stroke or transient ischaemic attack (TIA) and peripheral vascular disease (PVD) were estimated over a median 13.8 years follow-up. A higher proportion of subjects with FH diagnosis were on lipid-lowering treatment compared to undiagnosed subjects with FH characteristics (SB/DLC phenotype for definite FH). [Extracted from the article]