OBJECTIVES: To explore whether trial population characteristics modify treatment responses across various interventions, comparators and rheumatic conditions.

METHODS: In this meta-epidemiological study, we included trials from systematic reviews available from the Cochrane Musculoskeletal Group published up to 23 April 2019 in Cochrane Library with meta-analyses of five or more randomised controlled trials (RCTs) published from year 2000. From trial reports, we extracted data on 20 population characteristics. For characteristics with sufficient data (ie, available for ≥2/3 of the trials), we performed multilevel meta-epidemiological analyses.

RESULTS: We identified 19 eligible systematic reviews contributing 187 RCTs (212 comparisons). Only age and sex were explicitly reported in ≥2/3 of the trials. Using information about the country of the trials led to sufficient data for five further characteristics, that is, 7 out of 20 (35%) protocolised characteristics were analysed. The meta-regressions showed effect modification by economic status, place of residence, and, nearly, from healthcare system (explaining 4.8%, 0.9% and 1.5% of the between-trial variation, respectively). No effect modification was demonstrated from age, sex, patient education/health literacy or predominant religion.

CONCLUSIONS: This study demonstrates the scarce reporting of most population characteristics, hampering investigation of their impact with meta-research. Our sparse results suggest that place of residence (ie, continent of the trial), economic status (based on World Bank classifications) and healthcare system (based on WHO index for health system performance) may be important in explaining the variation in treatment response across trials. There is an urgent need for consistent reporting of important population characteristics in trials.

PROSPERO REGISTRATION NUMBER: CRD42019127642.

Background: A right hemicolectomy is among the most commonly performed operations for colon cancer, but modern high-quality, multination data addressing the morbidity and mortality rates are lacking. Objective: This study reports the morbidity and mortality rates for right-sided colon cancer and identifies predictors for unfavorable short-term outcome after right hemicolectomy. Design: This was a snapshot observational prospective study. Setting: The study was conducted as a multicenter international study. Patients: The 2015 European Society of Coloproctology snapshot study was a prospective multicenter international series that included all patients undergoing elective or emergency right hemicolectomy or ileocecal resection over a 2-month period in early 2015. This is a subanalysis of the colon cancer cohort of patients. Main Outcome Measures: Predictors for anastomotic leak and 30-day postoperative morbidity and mortality were assessed using multivariable mixed-effect logistic regression models after variables selection with the Lasso method. Results: Of the 2515 included patients, an anastomosis was performed in 97.2% (n = 2444), handsewn in 38.5% (n = 940) and stapled in 61.5% (n = 1504) cases. The overall anastomotic leak rate was 7.4% (180/2444), 30-day morbidity was 38.0% (n = 956), and mortality was 2.6% (n = 66). Patients with anastomotic leak had a significantly increased mortality rate (10.6% vs 1.6% no-leak patients; p ≥ 0.001). At multivariable analysis the following variables were associated with anastomotic leak: longer duration of surgery (OR = 1.007 per min; p = 0.0037), open approach (OR = 1.9; p = 0.0037), and stapled anastomosis (OR = 1.5; p = 0.041). Limitations: This is an observational study, and therefore selection bias could be present. For this reason, a multivariable logistic regression model was performed, trying to correct possible confounding factors. Conclusions: Anastomotic leak after oncologic right hemicolectomy is a frequent complication, and it is associated with increased mortality. The key contributing surgical factors for anastomotic leak were anastomotic technique, surgical approach, and duration of surgery.

OBJECTIVES: Cancer is associated with higher risk of stroke. Whether this translates into higher risk of cancer in stroke of an extent calling for cancer screening in stroke is unclear. We investigated prevalence and risk of occult cancer in stroke compared to the background population without history of stroke.

MATERIALS AND METHODS: All patients >40 years of age with incident stroke in Denmark 2003-2015 were identified through the Danish Stroke Registry (n = 85 893) and matched 1:10 on age and sex to the Danish background population without history of stroke (n = 858 740). Linking data to the Danish Cancer Registry, we determined prevalence of occult cancer in stroke defined as the event of previously unknown cancer during a 1-year follow-up in the stroke and in the background population. Cox regression models were used to study risk in comparison to the background population.

RESULTS: Prevalence (per 1000) of occult cancer in the stroke/background cohorts was 25.0/15.8 in women and 29.8/20.4 in men. Prevalence was dependent on age and sex. Highest among stroke patients aged 70-80 years (35.6 in women, 42.4 in men); lowest in patients aged 40-50 years (8.3 in women, 6.8 in men). Stroke was associated with an overall 54% higher risk of occult cancer but risk increased significantly with smoking, hazard ratio (HR) 1.47, age HR 1.27 per 10 years, male sex HR 1.25, and diabetes HR 1.25.

CONCLUSIONS: Prevalence and risk of occult cancer in stroke is considerable and calls for attention when designing the stroke investigation program.

The objective was to use accumulated evidence to explore the association between processed meat intake and risk of colorectal cancer (CRC) and to investigate the reliability of associations by evaluating patterns of risk by study population characteristics and research quality parameters. We included 29 observational prospective cohort studies with relative risk estimates and 95% confidence intervals for CRC according to various levels of processed meat consumption. Risk of bias was assessed using Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool. Data sources were PubMed and Embase up to January 2017. The summary relative risks for high versus low processed meat consumption and risk of CRC, colon, and rectal cancer were 1.13 (95% CI: 1.01, 1.26), 1.19 (95% CI: 1.09, 1.31), and 1.21 (95% CI: 0.98, 1.49), respectively. Similar estimates were observed for the dose-response analyses. Heterogeneity across studies was detected in most analytical models. The overall judgment showed that two out of 29 studies had a moderate risk of bias, 25 had a serious risk of bias, and 2 had a critical risk of bias. The bias domains most often rated critical were bias due to risk of confounding, bias due to missing data, and selective outcome reporting bias. Although this meta-analysis indicates a modest association between processed meat intake and an increased risk of CRC, our assessment of internal validity warrants a cautious interpretation of these results, as most of the included studies were judged to have serious or critical risks of bias.

BACKGROUND: There are difficulties in carrying out research in low-income urban communities, but the methodological challenges and suggestions on how to deal with them are often undocumented. The aims of this study are to describe the challenges of recruiting and enrolling low-income pregnant women with periodontitis to a clinical trial on vitamin D/calcium milk fortification and periodontal therapy and also to describe the patient-, study protocol- and setting-related factors related to women's ineligibility and refusal to participate in the study.

METHODS: A mixed-method sequential exploratory design was applied. Qualitative and quantitative data on recruitment to a 2 × 2 factorial feasibility clinical trial were used. Eighteen women attending the health centre in a low-income area in Duque de Caxias (Rio de Janeiro, Brazil) took part in focus group discussions, and the data were thematically analysed. Quantitative data were analysed using appropriate descriptive statistics, including absolute and relative frequencies.

RESULTS: Of all referrals (767), 548 (78.5%) did not meet the initial eligibility criteria. The main reason for exclusion (58%) was advanced gestational age (> 20 weeks) at first prenatal appointment. In the periodontal examination (dental screen), the main reason for exclusion was the presence of extensive caries (64 out of 127 exclusions). Non-participation of those eligible after the periodontal examination was approximately 24% (22 out 92 eligible women) and predominantly associated with patient-related barriers (e.g. transportation barriers, family obligations, patients being unresponsive to phone calls and disconnected telephones). The study recruited 70 women with periodontitis in 53 weeks and did not reach the benchmark of 120 women in 36 weeks (58.3% of the original target). Recruitment was severely hindered by health centre closures due to general strikes. The recruitment yields were 9.1% (70/767) of all women contacted at first prenatal visit and 76.1% (70/92) of those screened eligible and enrolled in the trial. Women did not report concerns regarding random allocation and considered fortified milk as a healthful and safe food for pregnant women. Some women reported that financial constraints (e.g. transportation costs) could hinder participation in the study.

CONCLUSION: Engagement between the research team and health centre staff (e.g. nurses) facilitated referral and recruitment, yet some pregnant women failed to participate in the study largely due to significant patient-related sociodemographic barriers and setting-related factors. Our data illustrate the complexity of overcoming recruitment and enrolment challenges for clinical trials in resource-limited settings.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT03148483. Registered on 11 May 2017.