Christopher C Winchester

Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review

Objective To update the findings of the 2005 systematic review of population-based studies assessing the epidemiology of gastro-oesophageal reflux disease (GERD). Design PubMed and Embase were screened for new references using the original search strings. Studies were required to be population-based, to include ≥200 individuals, to have response rates ≥50% and recall periods <12 months. GERD was defined as heartburn and/or regurgitation on at least 1 day a week, or according to the Montreal definition, or diagnosed by a clinician. Temporal and geographic trends in disease prevalence were examined using a Poisson regression model. Results 16 studies of GERD epidemiology published since the original review were found to be suitable for inclusion (15 reporting prevalence and one reporting incidence), and were added to the 13 prevalence and two incidence studies found previously. The range of GERD prevalence estimates was 18.1%–27.8% in North America, 8.8%–25.9% in Europe, 2.5%–7.8% in East Asia, 8.7%–33.1% in the Middle East, 11.6% in Australia and 23.0% in South America. Incidence per 1000 person-years was approximately 5 in the overall UK and US populations, and 0.84 in paediatric patients aged 1–17 years in the UK. Evidence suggests an increase in GERD prevalence since 1995 (p<0.0001), particularly in North America and East Asia. Conclusions GERD is prevalent worldwide, and disease burden may be increasing. Prevalence estimates show considerable geographic variation, but only East Asia shows estimates consistently lower than 10%.

Gastro-oesophageal reflux symptoms, oesophagitis and Barrett’s oesophagus in the general population: the Loiano–Monghidoro study

Objective: Existing endoscopy-based data on gastro-oesophageal reflux disease (GORD) in the general population are scarce. This study aimed to evaluate typical symptoms and complications of GORD, and their associated risk factors, in a representative sample of the Italian population. Methods: 1533 adults from two Italian villages were approached to undergo symptom assessment using a validated questionnaire and upper gastrointestinal endoscopy. Data were obtained from 1033 individuals (67.4% response rate). Results: The prevalence of reflux symptoms was 44.3%; 23.7% of the population experienced such symptoms on at least 2 days per week (frequent symptoms). The prevalence rates of oesophagitis and Barrett’s oesophagus in the population were 11.8% and 1.3%, respectively. Both frequent (relative risk (RR) 2.6; 95% confidence interval (CI) 1.7 to 3.9) and infrequent (RR 1.9; 95% CI 1.2 to 3.0) reflux symptoms were associated with the presence of oesophagitis. No reflux symptoms were reported by 32.8% of individuals with oesophagitis and 46.2% of those with Barrett’s oesophagus. Hiatus hernia was associated with frequent reflux symptoms and oesophagitis, and was present in 76.9% of those with Barrett’s oesophagus. We found no association between body mass index and reflux symptoms or oesophagitis. Conclusions: GORD is common in Italy, but the prevalence of Barrett’s oesophagus in the community is lower than has been reported in selected populations. Both frequent and infrequent reflux symptoms are associated with an increased risk of oesophagitis. Individuals with oesophagitis and Barrett’s oesophagus often have no reflux symptoms.

Heat shock protein 70 (Hsp70) stimulates proliferation and cytolytic activity of natural killer cells

We previously demonstrated that lysis of tumor cells that express Hsp70, the highly stress-inducible member of the HSP70 family, on their plasma membrane is mediated by natural killer (NK) cells. Here, we studied the effects of different proteins of the HSP70 family in combination with interleukin 2 (IL-2) on the proliferation and cytotoxic activity of human NK cells in vitro. Proliferation of NK cells was significantly enhanced by human recombinant Hsp70 (rHsp70) and to a lesser extent by rHsp70homC, the recombinant C-terminal peptide-binding domain derived from Hsp70hom, but not by the constitutive Hsc70 or DnaK, the Escherichia coli analogue of human Hsp70. Even rHsp70 protein alone moderately enhances proliferation and cytolytic activity of NK cells, thus indicating that the stimulatory effect is not strictly dependent on IL-2. NK cells stimulated with rHsp70 protein also exhibit an increased secretion of interferon gamma (IFN-gamma). The phenotypic characterization of NK cells with specificity for Hsp70-expressing tumor cells revealed a CD16dim/CD56bright and increased CD57 and CD94 expression. The cytolytic activity of NK cells also was significantly reduced when a CD94-specific antibody or rHsp70 was added directly before the cytotoxicity assay, whereas other antibodies directed against CD57 and major histocompatibility complex class I molecules or Hsp70 proteins, including Hsc70 and DnaK, did not affect the NK-mediated killing. However, long-term incubation of NK cells with rHsp70 protein enhances not only the proliferative but also the cytolytic response against Hsp70-expressing tumor cells. Our results indicate that the C-terminal domain of Hsp70 protein affects not only the proliferative but also the cytolytic activity of a phenotypically distinct NK cell population with specificity for Hsp70-expressing tumor cells. 1999 International Society for Experimental Hematology.

Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice – an evidence-based international guide

Evidence suggests that the gut microbiota play an important role in gastrointestinal problems.

Antibiotic Prescribing and Outcomes of Lower Respiratory Tract Infection in UK Primary Care

BACKGROUND Lower respiratory tract infection (LRTI) is common in the community and may result in hospitalization or death. This observational study aimed to investigate the role of antibiotics in the management of LRTI in the primary care setting in the United Kingdom. METHODS Patients receiving a first diagnosis of LRTI during 2004 and satisfying inclusion and data quality criteria were identified in the General Practice Research Database. Factors associated with respiratory infection-related hospital admissions and death in the 3 months following the initial diagnosis were identified using Cox proportional hazards regression. RESULTS Antibiotic prescribing on the day of diagnosis was associated with a decreased rate of respiratory infection-related hospital admission (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.58 to 0.92), while antibiotic prescribing in the previous 7 days (HR, 1.92; 95% CI, 1.24 to 2.96) and prior referral or hospitalization (HR, 1.48; 95% CI, 1.20 to 1.83) were associated with an increased risk of hospital admission. Female sex (HR, 0.73; 95% CI, 0.64 to 0.84), allergic rhinitis (HR, 0.48; 95% CI, 0.27 to 0.83), influenza vaccination (HR, 0.75; 95% CI, 0.65 to 0.87), prior inhaled corticosteroid use (HR, 0.63; 95% CI, 0.52 to 0.76), and antibiotic prescription on the day of diagnosis (HR, 0.31; 95% CI, 0.26 to 0.37) were associated with decreased respiratory infection-related mortality, while a Charlson comorbidity index of >or= 2 (HR, 2.24; 95% CI, 1.72 to 2.92), antibiotic prescription in the previous 7 days (HR, 1.56; 95% CI, 1.20 to 2.03), and frequent consultation (HR, 1.62; 95% CI, 1.09 to 2.40) were associated with increased mortality. CONCLUSIONS Antibiotic prescribing on the day of LRTI diagnosis was associated with reductions in hospital admissions and mortality related to respiratory infection. Antibiotics may help to prevent adverse outcomes for some patients with LRTI.

Professional medical writing support and the quality of randomised controlled trial reporting: a cross-sectional study

Objectives Authors may choose to work with professional medical writers when writing up their research for publication. We examined the relationship between medical writing support and the quality and timeliness of reporting of the results of randomised controlled trials (RCTs). Design Cross-sectional study. Study sample Primary reports of RCTs published in BioMed Central journals from 2000 to 16 July 2014, subdivided into those with medical writing support (n=110) and those without medical writing support (n=123). Main outcome measures Proportion of items that were completely reported from a predefined subset of the Consolidated Standards of Reporting Trials (CONSORT) checklist (12 items known to be commonly poorly reported), overall acceptance time (from manuscript submission to editorial acceptance) and quality of written English as assessed by peer reviewers. The effect of funding source and publication year was examined. Results The number of articles that completely reported at least 50% of the CONSORT items assessed was higher for those with declared medical writing support (39.1% (43/110 articles); 95% CI 29.9% to 48.9%) than for those without (21.1% (26/123 articles); 95% CI 14.3% to 29.4%). Articles with declared medical writing support were more likely than articles without such support to have acceptable written English (81.1% (43/53 articles); 95% CI 67.6% to 90.1% vs 47.9% (23/48 articles); 95% CI 33.5% to 62.7%). The median time of overall acceptance was longer for articles with declared medical writing support than for those without (167 days (IQR 114.5–231 days) vs 136 days (IQR 77–193 days)). Conclusions In this sample of open-access journals, declared professional medical writing support was associated with more complete reporting of clinical trial results and higher quality of written English. Medical writing support may play an important role in raising the quality of clinical trial reporting.

Systematic review: probiotics in the management of lower gastrointestinal symptoms - an updated evidence-based international consensus

In 2013, a systematic review and Delphi consensus reported that specific probiotics can benefit adult patients with irritable bowel syndrome (IBS) and other gastrointestinal (GI) problems.

Professional medical writing support and the reporting quality of randomized controlled trial abstracts among high-impact general medical journals

Background: In articles reporting randomized controlled trials, professional medical writing support is associated with increased adherence to Consolidated Standards of Reporting Trials (CONSORT). We set out to determine whether professional medical writing support was also associated with improved adherence to CONSORT for Abstracts. Methods: Using data from a previously published cross-sectional study of 463 articles reporting randomized controlled trials published between 2011 and 2014 in five top medical journals, we determined the association between professional medical writing support and CONSORT for Abstracts items using a Wilcoxon rank-sum test. Results: The mean proportion of adherence to CONSORT for Abstracts items reported was similar with and without professional medical writing support (64.3% vs 66.5%, respectively; p=0.30). Professional medical writing support was associated with lower adherence to reporting study setting (relative risk [RR]; 0.40; 95% confidence interval [CI], 0.23–0.70), and higher adherence to disclosing harms/side effects (RR 2.04; 95% CI, 1.37–3.03) and funding source (RR 1.75; 95% CI, 1.18–2.60). Conclusions: Although professional medical writing support was not associated with increased overall adherence to CONSORT for Abstracts, important aspects were improved with professional medical writing support, including reporting of adverse events and funding source. This study identifies areas to consider for improvement.

Development of a Collaborative European Pharmacoepidemiologic Post-Authorization Safety Study (PASS) Programme Examining Rivaroxaban Use in Routine Clinical Practice

Development of a Collaborative European Pharmacoepidemiologic Post-Authorization Safety Study (PASS) Programme Examining Rivaroxaban Use in Routine Clinical Practice

Open access policies of high impact medical journals: a cross-sectional study

Introduction Journal publishers increasingly offer governmental and charitable research funders the option to pay for open access with a Creative Commons Attribution (CC BY) licence, which allows sharing and adaptation of published materials for commercial as well as non-commercial use. The Open Access Scholarly Publishers Association recommends this licence as the least restrictive Creative Commons licence available. We set out to investigate whether pharmaceutical companies are offered the same options. Methods Using Journal Selector (Sylogent, Newtown, PA, USA), we identified journals with a 2015 impact factor of at least 15 on 24 May 2017, and excluded journals that only publish review articles from the analysis. Between 29 June 2017 and 26 July 2017, we collected information about the journals’ open access policies from their websites and/or by email contact. We contacted the journals by email again between 6 December 2017 and 2 January 2018 to confirm our findings. Results Thirty-seven non-review journals listed in the Journal Selector database, from 14 publishers, had a 2015 impact factor of at least 15. All 37 journals offered some form of access with varying embargo periods of up to 12 months. Of these journals, 23 (62%) offered immediate open access with a CC BY licence under certain circumstances (e.g. to specific research funders). Of these 23, only one journal confirmed that it offered a CC BY licence to commercial funders/pharmaceutical companies. Conclusion The open access policies of most medical journals with high impact factors restrict the dissemination of medical research funded by the pharmaceutical industry. To give the scientific community freedom to read, reuse and adapt medical publications, publishers and academic journal editors would ideally allow pharmaceutical companies to fund unrestricted and immediate open access with a CC BY licence.