Risk of stroke following herpes zoster: a self-controlled case-series study.

BACKGROUND: Herpes zoster is common and vaccine preventable. Stroke risk may be increased following zoster, but evidence is sparse and could be explained by differences between people with and without zoster. Our objective was to determine if stroke risk is increased following zoster. METHODS: Within-person comparisons were undertaken using the self-controlled case-series method and data from the UK Clinical Practice Research Datalink (1987-2012). Participants had a first-ever diagnosis of zoster and stroke within the study period. Stroke incidence in periods following zoster was compared with incidence in other time periods. Age-adjusted incidence ratios (IRs) and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 6584 individuals were included. Stroke rate was increased following zoster compared with the baseline unexposed period, then gradually reduced over 6 months: weeks 1-4 (age-adjusted IR, 1.63; 95% CI, 1.32-2.02), weeks 5-12 (IR, 1.42; 95% CI, 1.21-1.68), and weeks 13-26 (IR, 1.23; 95% CI, 1.07-1.42), with no increase thereafter. A stronger effect was observed for individuals with zoster ophthalmicus, rising to a >3-fold rate 5-12 weeks after zoster. Oral antivirals were given to 55% of individuals: IRs for stroke were lower among those receiving antivirals compared with those not treated, suggesting a protective effect. CONCLUSIONS: We have established an increased stroke rate within 6 months following zoster. Findings have implications for zoster vaccination programs, which may reduce stroke risk following zoster. The low antiviral prescribing rate needs to be improved; our data suggest that antiviral therapy may lead to a reduced stroke risk following zoster

Reporting transparency: making the ethical mandate explicit.

Improving the transparency and quality of reporting in biomedical research is considered ethically important; yet, this is often based on practical reasons such as the facilitation of peer review. Surprisingly, there has been little explicit discussion regarding the ethical obligations that underpin reporting guidelines. In this commentary, we suggest a number of ethical drivers for the improved reporting of research. These ethical drivers relate to researcher integrity as well as to the benefits derived from improved reporting such as the fair use of resources, minimizing risk of harms, and maximizing benefits. Despite their undoubted benefit to reporting completeness, questions remain regarding the extent to which reporting guidelines can influence processes beyond publication, including researcher integrity or the uptake of scientific research findings into policy or practice. Thus, we consider investigation on the effects of reporting guidelines an important step in providing evidence of their benefits

Zoster vaccination is associated with a reduction of zoster in elderly patients with chronic kidney disease.

BACKGROUND: Growing epidemiological evidence demonstrates increased zoster risks in people with chronic kidney disease (CKD). Study objectives were to determine zoster vaccine effectiveness in individuals with CKD in pragmatic use. METHODS: A population-based cohort study was undertaken in a 5% random sample of US Medicare from 2007 to 2009 involving 766 330 eligible individuals aged ≥65 years who were (29 785) and were not (736 545) exposed to the zoster vaccine. Incidence rates for zoster in vaccinated and unvaccinated individuals and hazard ratios for zoster comparing vaccinated with unvaccinated were determined for individuals with CKD. Time-updated Cox proportional hazards models were used, adjusting for relevant confounders. RESULTS: CKD was present in 183 762 (24%) of individuals (15% of vaccinees). Adjusted vaccine effectiveness [95% confidence intervals (CIs)] in individuals with CKD was 0.49 (0.36-0.65). The adjusted vaccine effectiveness in participants with both CKD and diabetes mellitus was 0.46 (95% CI 0.09-0.68). Vaccine effectiveness estimates were similar to those previously reported for the general population [vaccine effectiveness 0.48 (95% CI 0.39-0.56)]. CONCLUSIONS: Zoster vaccine is effective against incident zoster in older individuals with CKD. Extra efforts are warranted to increase vaccine uptake in individuals with CKD given the known low uptake in these higher risk individuals

Association between eczema and major cardiovascular outcomes in population-based studies: a systematic review protocol.

INTRODUCTION: Chronic inflammatory diseases such as eczema (also known as atopic dermatitis) have been inconsistently linked to cardiovascular disease and stroke in both mechanistic and epidemiological studies. There is a need to review the existing epidemiological data examining the association between eczema and major cardiovascular outcomes, including angina, myocardial infarction, coronary revascularisation, heart failure, cardiac arrhythmias, stroke and cardiovascular death, in order to improve our understanding of the comorbidities of eczema. METHODS AND ANALYSIS: We will systematically review population-based studies, including cohort, case-control and cross-sectional studies, reporting on the association between eczema and cardiovascular outcomes. We will search Medline, Embase and Global Health, from their date of inception to April 2017, using a comprehensive search strategy formulated with the help of a librarian. Two reviewers will independently screen titles and abstracts in duplicate, followed by independent data extraction and quality assessment. We will group studies by the cardiovascular outcome under study and synthesise them narratively. If sufficient numbers of homogeneous studies are returned, we will perform meta-analyses to obtain pooled effect estimates. Preferred Reporting Items for Systematic Review and Meta-Analysis will be used to inform the reporting of this study. TRIAL REGISTRATION NUMBER: CRD42017060359

Association between eczema and major cardiovascular outcomes in population-based studies: a systematic review protocol.

INTRODUCTION: Chronic inflammatory diseases such as eczema (also known as atopic dermatitis) have been inconsistently linked to cardiovascular disease and stroke in both mechanistic and epidemiological studies. There is a need to review the existing epidemiological data examining the association between eczema and major cardiovascular outcomes, including angina, myocardial infarction, coronary revascularisation, heart failure, cardiac arrhythmias, stroke and cardiovascular death, in order to improve our understanding of the comorbidities of eczema. METHODS AND ANALYSIS: We will systematically review population-based studies, including cohort, case-control and cross-sectional studies, reporting on the association between eczema and cardiovascular outcomes. We will search Medline, Embase and Global Health, from their date of inception to April 2017, using a comprehensive search strategy formulated with the help of a librarian. Two reviewers will independently screen titles and abstracts in duplicate, followed by independent data extraction and quality assessment. We will group studies by the cardiovascular outcome under study and synthesise them narratively. If sufficient numbers of homogeneous studies are returned, we will perform meta-analyses to obtain pooled effect estimates. Preferred Reporting Items for Systematic Review and Meta-Analysis will be used to inform the reporting of this study. TRIAL REGISTRATION NUMBER: CRD42017060359

Phosphodiesterase Type 5 Inhibitors and Risk of Malignant Melanoma: Matched Cohort Study Using Primary Care Data from the UK Clinical Practice Research Datalink.

BACKGROUND: Laboratory evidence suggests that reduced phosphodiesterase type 5 (PDE5) expression increases the invasiveness of melanoma cells; hence, pharmacological inhibition of PDE5 could affect melanoma risk. Two major epidemiological studies have investigated this and come to differing conclusions. We therefore aimed to investigate whether PDE5 inhibitor use is associated with an increased risk of malignant melanoma, and whether any increase in risk is likely to represent a causal relationship. METHODS AND FINDINGS: We conducted a matched cohort study using primary care data from the UK Clinical Practice Research Datalink. All men initiating a PDE5 inhibitor and with no prior cancer diagnosis were identified and matched on age, diabetes status, and general practice to up to four unexposed controls. Ever use of a PDE5 inhibitor and time-updated cumulative number of PDE5 inhibitor prescriptions were investigated as exposures, and the primary outcome was malignant melanoma. Basal cell carcinoma, solar keratosis, and colorectal cancer were investigated as negative control outcomes to exclude bias. Hazard ratios (HRs) were estimated from Cox models stratified by matched set and adjusted for potential confounders. 145,104 men with ≥1 PDE5 inhibitor prescription, and 560,933 unexposed matched controls were included. In total, 1,315 incident malignant melanoma diagnoses were observed during 3.44 million person-years of follow-up (mean 4.9 y per person). After adjusting for potential confounders, there was weak evidence of a small positive association between PDE5 inhibitor use and melanoma risk (HR = 1.14, 95% CI 1.01-1.29, p = 0.04). A similar increase in risk was seen for the two negative control outcomes related to sun exposure (HR = 1.15, 95% CI 1.11-1.19, p < 0.001, for basal cell carcinoma; HR = 1.21, 95% CI 1.17-1.25, p < 0.001, for solar keratosis), but there was no increased risk for colorectal cancer (HR = 0.91, 95% CI 0.85-0.98, p = 0.01). There was no evidence that risk increased with number of prescriptions received (p-trend = 0.83). In a post hoc analysis, there was strong evidence that solar keratosis was associated with future PDE5 inhibitor use (odds ratio = 1.28, 95% CI 1.23-1.34, p < 0.001), suggesting that men with higher sun exposure were more likely to become PDE5 inhibitor users. However, a limitation of our study was that we did not have individual-level data on sun exposure, so we could not directly control for this in the primary analysis. CONCLUSIONS: Our results were not consistent with PDE5 inhibitors being causally associated with melanoma risk, and strongly suggest that observed risk increases are driven by greater sun exposure among patients exposed to a PDE5 inhibitor

Retraction of COVID-19 Pharmacoepidemiology Research Could Have Been Avoided by Effective Use of Reporting Guidelines.

INTRODUCTION: Two recent high-profile publications (and subsequent retractions) of pharmacoepidemiology studies reporting the effectiveness and risk of hydroxychloroquine in COVID-19 patients received international media attention. Transparent and complete reporting of these studies could have provided peer reviewers and editors with sufficient information to question the methods used and the validity of results. Since these studies used routinely collected health data, the guidelines for the REporting of studies Conducted using Observational Routinely collected health Data (RECORD) should have been applied to ensure complete reporting of the research. METHODS: We evaluated the two retracted articles for completeness of reporting using the RECORD for Pharmacoepidemiology (RECORD-PE) checklist, which includes the checklists for the STengthening the Reporting of OBservational studies in Epidemiology (STROBE) and RECORD. We compared the proportion of STROBE, RECORD and RECORD-PE items adequately reported using Chi-squared statistics. RESULTS: In the article published by The Lancet, 29 of 34 STROBE items (85.3%) were adequately reported, compared with 3.5 of 13 RECORD items (26.9%) and 9.5 of 15 RECORD-PE items (63.3%)(χ2 = 14.839, P <0.001). Similarly, the article published in NEJM reported 24 of 34 STROBE items (70.6%), two of 13 RECORD items (15.4%), and 7.5 of 15 RECORD-PE items (50.0%) (χ2 = 11.668, P = 0.003). Important aspects of the methods unique to research using routinely collected health data were not reported, including variables used to identify exposure, outcome and confounders, validation of the coding or algorithms, a description of the underlying database population and the accuracy of data linkage methods. DISCUSSION: While STROBE items were generally adequately reported, RECORD and RECORD-PE items were not. Reporting guidelines should be effectively implemented in order for transparency and completeness of research manuscripts, allowing for adequate evaluation by editors and peer reviewers