Evidence Of Difference In Risk Research Articles

Designing target trials using electronic health records: A case study of second-line disease-modifying anti-rheumatic drugs and cardiovascular disease outcomes in patients with rheumatoid arthritis.

Emulation of the "target trial" (TT), a hypothetical pragmatic randomized controlled trial (RCT), using observational data can be used to mitigate issues commonly encountered in comparative effectiveness research (CER) when randomized trials are not logistically, ethically, or financially feasible. However, cardiovascular (CV) health research has been slow to adopt TT emulation. Here, we demonstrate the design and analysis of a TT emulation using electronic health records to study the comparative effectiveness of the addition of a disease-modifying anti-rheumatic drug (DMARD) to a regimen of methotrexate on CV events among rheumatoid arthritis (RA) patients. We used data from an electronic medical records-based cohort of RA patients from Northwestern Medicine to emulate the TT. Follow-up began 3 months after initial prescription of MTX (2000-2020) and included all available follow-up through June 30, 2020. Weighted pooled logistic regression was used to estimate differences in CVD risk and survival. Cloning was used to handle immortal time bias and weights to improve baseline and time-varying covariate imbalance. We identified 659 eligible people with RA with average follow-up of 46 months and 31 MACE events. The month 24 adjusted risk difference for MACE comparing initiation vs non-initiation of a DMARD was -1.47% (95% confidence interval [CI]: -4.74, 1.95%), and the marginal hazard ratio (HR) was 0.72 (95% CI: 0.71, 1.23). In analyses subject to immortal time bias, the HR was 0.62 (95% CI: 0.29-1.44). In this sample, we did not observe evidence of differences in risk of MACE, a finding that is compatible with previously published meta-analyses of RCTs. Thoughtful application of the TT framework provides opportunities to conduct CER in observational data. Benchmarking results of observational analyses to previously published RCTs can lend credibility to interpretation.

Bleeding and venous thromboembolism events in cancer patients taking direct oral anticoagulants vs. low molecular weight heparin

IntroductionPatients with cancer have an increased risk of developing venous thromboembolism (VTE), and subsequently a higher risk of bleeding secondary to anticoagulants. Low-molecular weight heparin (LMWH) has been the standard of care for these patients, with emerging data on the use of direct oral anticoagulants (DOACs). The primary objective of the study was to determine the prevalence of major bleeding events in cancer patients taking DOACs or LMWH for VTE. Secondary objectives included the rate of first VTE recurrence and the effect of concomitant antiplatelet agents and/or significant drug interactions on major bleeding or recurrent VTE. Materials and methodsUsing the electronic medical record at the University of Rochester Medical Center, we retrospectively identified adult patients with active malignancy who had a diagnosis of VTE requiring therapeutic anticoagulation within the study period of July 1st, 2015 to June 1st, 2019. Patients were excluded if they were receiving prophylactic doses of LMWH per the institution VTE guidelines. Data on anticoagulant medications were collected as well as information on major bleeding and recurrent VTE events. Results and conclusionsThere is insufficient evidence of difference in risk of major bleeding among patients who received a DOAC vs LMWH (cause-specific hazard ratio (HR) = 0.77, 95% CI 0.29–2.04, P = 0.60). There was also no evidence of a difference in risk of recurrent VTE between patients who received DOAC vs. LMWH (cause-specific HR = 0.98, 95% CI 0.15–6.26, P = 0.98). These results suggest that DOACs are not significantly less safe than LMWH for patients with cancer.

Heated tobacco products for smoking cessation and reducing smoking prevalence.

Heated tobacco products for smoking cessation and reducing smoking prevalence.

Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts

ObjectivesTo assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform.MethodsWe conducted two cohort studies from 1 March to 14...

Parental education and the risk of cerebral palsy for children: an evaluation of causality.

To explore whether increasing parental education has a causal effect on risk of cerebral palsy (CP) in the child, or whether unobserved confounding is a more likely explanation. We used data from Norwegian registries on approximately 1.5million children born between 1967 and 2011. We compared results from a traditional cohort design with results from a family-based matched case-control design, in which children with CP were matched to their first cousins without CP. In addition, we performed a simulation study to assess the role of unobserved confounding. In the cohort design, the odds of CP were reduced in children of mothers and fathers with higher education (adjusted odds ratio [OR] 0.67, 95% confidence interval [CI] 0.60-0.75 for maternal education, and adjusted OR 0.75, 95% CI 0.67-0.85 for paternal education). In the family-based case-control design, only an association for maternal education remained (adjusted OR 0.80, 95% CI 0.64-0.99). Results from a simulation study suggested that this association could be explained by unobserved confounding. A causal effect of obtaining higher education on risk of CP in the child is unlikely. Results stress the importance of continued research on the role of genetic and environmental risk factors that vary by parents' educational level. Children of higher-educated parents had significantly lower odds of cerebral palsy (CP). There was no evidence of difference in risk of CP within first cousins whose mothers or fathers had different educational levels. Association between parental education and odds of CP did not reflect a causal effect.

Incidence of prostate and urological cancers in England by ethnic group, 2001-2007: a descriptive study.

BackgroundThe aetiology of urological cancers is poorly understood and variations in incidence by ethnic group may provide insights into the relative importance of genetic and environmental risk factors. Our objective was to compare the incidence of four urological cancers (kidney, bladder, prostate and testicular) among six ‘non-White’ ethnic groups in England (Indian, Pakistani, Bangladeshi, Black African, Black Caribbean and Chinese) to each other and to Whites.MethodsWe obtained Information on ethnicity for all urological cancer registrations from 2001 to 2007 (n = 329,524) by linkage to the Hospital Episodes Statistics database. We calculated incidence rate ratios adjusted for age, sex and income, comparing the six ethnic groups (and combined ‘South Asian’ and ‘Black’ groups) to Whites and to each other.ResultsThere were significant differences in the incidence of all four cancers between the ethnic groups (all p < 0.001). In general, ‘non-White’ groups had a lower incidence of urological cancers compared to Whites, except prostate cancer, which displayed a higher incidence in Blacks. (IRR 2.55) There was strong evidence of differences in risk between Indians, Pakistanis and Bangladeshis for kidney, bladder and prostate cancer (p < 0.001), and between Black Africans and Black Caribbeans for all four cancers (p < 0.001).ConclusionsThe risk of urological cancers in England varies greatly by ethnicity, including within groups that have traditionally been analysed together (South Asians and Blacks). In general, these differences are not readily explained by known risk factors, although the very high incidence of prostate cancer in both black Africans and Caribbeans suggests increased genetic susceptibility. g.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1771-2) contains supplementary material, which is available to authorized users.

Manual small incision cataract surgery (MSICS) with posterior chamber intraocular lens versus extracapsular cataract extraction (ECCE) with posterior chamber intraocular lens for age-related cataract.

Age-related cataract is the opacification of the lens, which occurs as a result of denaturation of lens proteins. Age-related cataract remains the leading cause of blindness globally, except in the most developed countries. A key question is what is the best way of removing the lens, especially in lower income settings. To compare two different techniques of lens removal in cataract surgery: manual small incision surgery (MSICS) and extracapsular cataract extraction (ECCE). We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 8), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to September 2014), EMBASE (January 1980 to September 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to September 2014), Web of Science Conference Proceedings Citation Index- Science (CPCI-S), (January 1990 to September 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 23 September 2014. We included randomised controlled trials (RCTs) only. Participants in the trials were people with age-related cataract. We included trials where MSICS with a posterior chamber intraocular lens (IOL) implant was compared to ECCE with a posterior chamber IOL implant. Data were collected independently by two authors. We aimed to collect data on presenting visual acuity 6/12 or better and best-corrected visual acuity of less than 6/60 at three months and one year after surgery. Other outcomes included intraoperative complications, long-term complications (one year or more after surgery), quality of life, and cost-effectiveness. There were not enough data available from the included trials to perform a meta-analysis. Three trials randomly allocating people with age-related cataract to MSICS or ECCE were included in this review (n = 953 participants). Two trials were conducted in India and one in Nepal.Trial methods, such as random allocation and allocation concealment, were not clearly described; in only one trial was an effort made to mask outcome assessors. The three studies reported follow-up six to eight weeks after surgery. In two studies, more participants in the MSICS groups achieved unaided visual acuity of 6/12 or 6/18 or better compared to the ECCE group, but overall not more than 50% of people achieved good functional vision in the two studies. 10/806 (1.2%) of people enrolled in two trials had a poor outcome after surgery (best-corrected vision less than 6/60) with no evidence of difference in risk between the two techniques (risk ratio (RR) 1.58, 95% confidence interval (CI) 0.45 to 5.55). Surgically induced astigmatism was more common with the ECCE procedure than MSICS in the two trials that reported this outcome. In one study there were more intra- and postoperative complications in the MSICS group. One study reported that the costs of the two procedures were similar. There are no other studies from other countries other than India and Nepal and there are insufficient data on cost-effectiveness of each procedure.Better evidence is needed before any change may be implemented. Future studies need to have longer-term follow-up and be conducted to minimize biases revealed in this review with a larger sample size to allow examination of adverse events.

Incidence of gastrointestinal cancers by ethnic group in England, 2001–2007

ObjectiveTo compare the incidence of six gastrointestinal cancers (colorectal, oesophageal, gastric, liver, gallbladder and pancreatic) among the six main ‘non-White’ ethnic groups in England (Indian, Pakistani, Bangladeshi, Black African, Black...

Modelling prior reproductive history to improve prediction of risk for very preterm birth

In published studies of preterm birth, analyses have usually been centred on individual reproductive events and do not account for the joint distributions of these events. In particular, spontaneous and induced abortions have often been studied separately and have been variously reported as having no increased risk, increased risk or different risks for subsequent preterm birth. In order to address this inconsistency, we categorised women into mutually exclusive groups according to their reproductive history, and explored the range of risks associated with different reproductive histories and assessed similarities of risks between different pregnancy histories. The data were from a population-based case-control study, conducted in Victoria, Australia. The study recruited women giving birth between April 2002 and April 2004 from 73 maternity hospitals. Detailed reproductive histories were collected by interview a few weeks after the birth. The cases were 603 women who had had a singleton birth between 20 and less than 32 weeks gestation (very preterm births including terminations of pregnancy) and the controls were 796 randomly selected women from the population who had had a singleton birth of at least 37 completed weeks gestation. All birth outcomes were included. Unconditional logistic regression was used to assess the association of very preterm birth with type and number of prior abortions, prior preterm births and sociodemographic factors. Using the complex combinations of prior pregnancy experiences of women (including nulligravidity), we showed that a history of prior childbirth (at term) with no preterm births gave the lowest risk of very preterm birth. With this group as the reference category, odds ratios of more than two were associated with all other prior reproductive histories. There was no evidence of difference in risk between types of abortion (i.e. spontaneous or induced) although the risk increased if a prior preterm birth had also occurred. There was an increasing risk of very preterm birth associated with increasing numbers of abortions. This method of data analysis reveals consistent and similar risks for very preterm birth following spontaneous or induced abortions. The findings point to the need to explore commonalities rather than differences in regard to the impact of abortion on subsequent births.

A single nucleotide polymorphism in the E-cadherin gene promoter-160 is not associated with risk of Korean gastric cancer.

Recently, the -160 C/A polymorphism, located within the regulatory region of Ecadherin promoter, has been shown to influence E-cadherin transcription by altering transcription factor binding. We examined the effect of this polymorphism on risk of gastric cancer and on histological classification of intestinal- and diffuse-type gastric cancer in 146 normal healthy individuals and 292 Korean gastric cancer patients. Genomic DNA samples were examined by polymerase chain reaction (PCR)-single strand conformational polymorphism (SSCP)-sequencing and confirmed by restriction fragment length polymorphism (RFLP). Unexpectedly, there was no significant difference in the genotype frequencies of the polymorphism between normal control and gastric cancer patients (x(2) test, p=0.433). The estimated odd ratio of C/C to A/A genotype in gastric cancer cases was 1.07 (95% confidence interval, 0.396-2.870). We also found no evidence for differences in risk for the intestinal- and diffuse-type gastric cancer. These results suggest that the -160 C/A polymorphism of the E-cadherin has no direct effect on the risk of Korean gastric cancer development and on its histological classification.

CDH1 c-160a promotor polymorphism is not associated with risk of stomach cancer.

We have combined data from case control studies designed to test the hypothesis that the c-160a promotor polymorphism in the gene coding for the cell adhesion molecule E-cadherin (CDH1) is associated with stomach cancer. A total of 899 individuals (433 patients and 466 controls) were analyzed. The genotype frequencies did not differ significantly between cases and controls, and the genotype-specific risks were not significantly different from unity, with an odds ratio for heterozygotes compared with the common homozygote of 1.3 (95% CI 0.98-1.8) and 1.2 (0.68-2.0) for rare homozygotes compared with common homozygotes. We found no evidence for differences in risk for the intestinal- and diffuse-type histopathologic subgroups.

Risk of congenital anomalies near hazardous-waste landfill sites in Europe: the EUROHAZCON study

Waste-disposal sites are a potential hazard to health. This study is a multicentre case-control study of the risk of congenital anomalies associated with residence near hazardous-waste landfill sites in Europe. We used data from seven regional registers of congenital anomalies in five countries. We studied 1089 livebirths, stillbirths, and terminations of pregnancy with non-chromosomal congenital anomalies and 2366 control births without malformation, whose mothers resided within 7 km of a landfill site; 21 sites were included. A zone within 3 km radius of each site was defined as the "proximate zone" of most likely exposure to teratogens. Residence within 3 km of a landfill site was associated with a significantly raised risk of congenital anomaly (295 cases/511 controls living 0-3 km from sites, 794/1855 living 3-7 km from sites; combined odds ratio 1.33 [95% CI 1.11-1.59], adjusted for maternal age and socioeconomic status). There was a fairly consistent decrease in risk with distance away from the sites. A significantly raised odds ratio for residence within 3 km of a landfill site was found for neural-tube defects (odds ratio 1.86 [1.24-2.79]), malformations of the cardiac septa (1.49 [1.09-2.04]), and anomalies of great arteries and veins (1.81 [1.02-3.20]). Odds ratios of borderline significance were found for tracheo-oesophageal anomalies (2.25 [0.96-5.26]), hypospadias (1.96 [0.98-3.92]), and gastroschisis (3.19 [0.95-10.77]). There was little evidence of differences in risk between landfill sites but power to detect such differences was low. This study shows a raised risk of congenital anomaly in babies whose mothers live close to landfill sites that handle hazardous chemical wastes, although there is a need for further investigation of whether the association of raised risk of congenital anomaly and residence near landfill sites is a causal one. Apparent differences between malformation subgroups should be interpreted cautiously.