The self-controlled case series (SCCS) is a useful design for investigating associations between outcomes and transient exposures. The SCCS design controls for all fixed covariates, but effect ...modification can still occur. This can be evaluated by including interaction terms in the model which, when exponentiated, can be interpreted as a relative incidence ratio (RIR): the change in relative incidence (RI) for a unit change in an effect modifier.
We conducted a scoping review to investigate the use of RIRs in published primary SCCS studies, and conducted a case-study in one of our own primary SCCS studies to illustrate the use of RIRs within an SCCS analysis to investigate subgroup effects in the context of comparing whole cell (wcp) and acellular (acp) pertussis vaccines. Using this case study, we also illustrated the potential utility of RIRs in addressing the healthy vaccinee effect (HVE) in vaccine safety surveillance studies.
Our scoping review identified 122 primary studies reporting an SCCS analysis. Of these, 24 described the use of interaction terms to test for effect modification. 21 of 24 studies reported stratum specific RIs, 22 of 24 reported the p-value for interaction, and less than half (10 of 24) reported the estimate of the interaction term/RIR, the stratum specific RIs and interaction p-values. Our case-study demonstrated that there was a nearly two-fold greater RI of ER visits and admissions following wcp vaccination relative to acp vaccination (RIR = 1.82, 95 % CI 1.64-2.01), where RI estimates in each subgroup were clearly impacted by a strong healthy vaccinee effect.
We demonstrated in our scoping review that calculating RIRs is not a widely utilized strategy. We showed that calculating RIRs across time periods is useful for the detection of relative changes in adverse event rates that might otherwise be missed due to the HVE. Many published studies of vaccine-associated adverse events could have missed/underestimated important safety signals masked by the HVE. With further development, our application of RIRs could be an important tool to address the HVE, particularly in the context of self-controlled study designs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PurposeTo investigate the robustness and longevity of SARS-CoV-2 immune responses conferred by natural infection and vaccination among priority populations such as immunocompromised individuals and ...people with post-acute sequelae of COVID-19 in a prospective cohort study (Stop the Spread Ottawa—SSO) in adults living in the Ottawa region. In this paper, we describe the study design, ongoing data collection and baseline characteristics of participants.ParticipantsSince October 2020, participants who tested positive for COVID-19 (convalescents) or at high risk of exposure to the virus (under surveillance) have provided monthly blood and saliva samples over a 10-month period. As of 2 November 2021, 1026 adults had completed the baseline survey and 976 had attended baseline bloodwork. 300 participants will continue to provide bimonthly blood samples for 24 additional months (ie, total follow-up of 34 months).Findings to dateThe median age of the baseline sample was 44 (IQR 23, range: 18–79) and just over two-thirds (n=688; 67.1%) were female. 255 participants (24.9%) had a history of COVID-19 infection confirmed by PCR and/or serology. Over 600 participants (60.0%) work in high-risk occupations (eg, healthcare, teaching and transportation). 108 participants (10.5%) reported immunocompromising conditions or treatments at baseline (eg, cancer, HIV, other immune deficiency, and/or use of immunosuppressants).Future plansSSO continues to yield rich research potential, given the collection of pre-vaccine baseline data and samples from the majority of participants, recruitment of diverse subgroups of interest, and a high level of participant retention and compliance with monthly sampling. The 24-month study extension will maximise opportunities to track SARS-CoV-2 immunity and vaccine efficacy, detect and characterise emerging variants, and compare subgroup humoral and cellular response robustness and persistence.
Melanoma represents an important public health problem, due to its high case-fatality rate. Identification of individuals at high risk would be of major interest to improve early diagnosis and ...ultimately survival. The aim of this study was to evaluate whether
variants predicted melanoma risk independently of at-risk phenotypic characteristics.
Data were collected within an international collaboration - the M-SKIP project. The present pooled analysis included data on 3,830 single, primary, sporadic, cutaneous melanoma cases and 2,619 controls from seven previously published case-control studies. All the studies had information on
gene variants by sequencing analysis and on hair color, skin phototype, and freckles, ie, the phenotypic characteristics used to define the red hair phenotype.
The presence of any
variant was associated with melanoma risk independently of phenotypic characteristics (OR 1.60; 95% CI 1.36-1.88). Inclusion of
variants in a risk prediction model increased melanoma predictive accuracy (area under the receiver-operating characteristic curve) by 0.7% over a base clinical model (
=0.002), and 24% of participants were better assessed (net reclassification index 95% CI 20%-30%). Subgroup analysis suggested a possibly stronger role of
in melanoma prediction for participants without the red hair phenotype (net reclassification index: 28%) compared to paler skinned participants (15%).
The authors suggest that measuring the
genotype might result in a benefit for melanoma prediction. The results could be a valid starting point to guide the development of scientific protocols assessing melanoma risk prediction tools incorporating the
genotype.
The transition from childhood to adolescence is associated with an increase in rates of some psychiatric disorders, including major depressive disorder, a debilitating mood disorder. The aim of this ...systematic review is to update the evidence on the benefits and harms of screening for depression in primary care and non-mental health clinic settings among children and adolescents.
This review is an update of a previous systematic review, for which the last search was conducted in 2017. We searched Ovid MEDLINE® ALL, Embase Classic+Embase, PsycINFO, Cochrane Central Register of Controlled Trials, and CINAHL on November 4, 2019, and updated on February 19, 2021. If no randomized controlled trials were found, we planned to conduct an additional search for non-randomized trials with a comparator group. For non-randomized trials, we applied a non-randomized controlled trial filter and searched the same databases except for Cochrane Central Register of Controlled Trials from January 2015 to February 2021. We also conducted a targeted search of the gray literature for unpublished documents. Title and abstract, and full-text screening were completed independently by pairs of reviewers.
In this review update, we were unable to find any randomized controlled studies that satisfied our eligibility criteria and evaluated the potential benefits and harms of screening for depression in children and adolescents. Additionally, a search for non-randomized trials yielded no studies that met the inclusion criteria.
The findings of this review indicate a lack of available evidence regarding the potential benefits and harms of screening for depression in children and adolescents. This absence of evidence emphasizes the necessity for well-conducted clinical trials to evaluate the effectiveness of depression screening among children and adolescents in primary care and non-mental health clinic settings.
PROSPERO CRD42020150373 .
Background
Nonsyndromic cleft lip with or without cleft palate (nsCL±P) and nonsyndromic cleft palate (nsCP) are caused by a combination of genetic and environmental risk factors. We investigated ...gene-environment and gene-gene joint effects in a large multicenter study of case-parent triads.
Methods
The nsCL±P or nsCP triads were recruited in 11 European countries between 2001 and 2005. We collected DNA samples from infants and from their mothers and fathers, and mothers completed a questionnaire on exposures, including smoking and folic acid supplement use during pregnancy. We used log-linear regression to estimate relative risks (RRs) and 95% confidence intervals (CIs) for associations between nsCL±P or nsCP and variants in MTHFR, MTHFD1, TGFA, SATB2, and MSX1, stratifying by environmental or genetic factors.
Results
We obtained genotype and exposure data for 728 nsCL±P triads and 292 nsCP triads. In male infants, there was no association between the mother's homozygous MSX1 p(CA) ∗4/∗4 genotype and nsCL±P (RR, 0.98; 95% CI, 0.63–1.54), but this maternal genotype resulted in a doubling of risk for female infants (RR, 2.21; 95% CI, 1.13–4.34). There was evidence suggestive of gene-gene joint-effects between MTHFR-TGFA for nsCP but not for nsCL±P.
Conclusion
Although we chose the genes and their variants and putative joint effects based on associations previously reported in the literature, we replicated few associations. These results do not provide evidence supporting associations between these genes and oral clefts in European populations, although gene-environment and gene-gene interactions could play a role in oral cleft etiology.
IntroductionHealth inequities are defined as unfair and avoidable differences in health between groups within a population. Most health research is conducted through observational studies, which are ...able to offer real-world insights about etiology, healthcare policy/programme effectiveness and the impacts of socioeconomic factors. However, most published reports of observational studies do not address how their findings relate to health equity. Our team seeks to develop equity-relevant reporting guidance as an extension of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. This scoping review will inform the development of candidate items for the STROBE-Equity extension. We will operationalise equity-seeking populations using the PROGRESS-Plus framework of sociodemographic factors. As part of a parallel stream of the STROBE-Equity project, the relevance of candidate guideline items to Indigenous research will be led by Indigenous coinvestigators on the team.Methods and analysisWe will follow the Joanna Briggs Institute method for conducting scoping reviews. We will evaluate the extent to which the identified guidance supports or refutes our preliminary candidate items for reporting equity in observational studies. These candidate items were developed based on items from equity-reporting guidelines for randomised trials and systematic reviews, developed by members of this team. We will consult with our knowledge users, patients/public partners and Indigenous research steering committee to invite suggestions for relevant guidance documents and interpretation of findings. If the identified guidance suggests the need for additional candidate items, they will be developed through inductive thematic analysis.Ethics and disseminationWe will follow a principled approach that promotes ethical codevelopment with our community partners, based on principles of cultural safety, authentic partnerships, addressing colonial structures in knowledge production and the shared ownership, interpretation, and dissemination of research. All products of this research will be published as open access.
Background Newborn screening (NBS) for sickle cell disease incidentally identifies heterozygous carriers of hemoglobinopathy mutations. In Ontario, Canada, these carrier results are not routinely ...disclosed, presenting an opportunity to investigate the potential health implications of carrier status. We aimed to compare rates of health services use among children identified as carriers of hemoglobinopathy mutations and those who received negative NBS results. Methods Eligible children underwent NBS in Ontario from October 2006 to March 2010 and were identified as carriers or as screen-negative controls, matched to carriers 5:1 based on neighbourhood and timing of birth. We used health care administrative data to determine frequencies of inpatient hospitalizations, emergency department (ED) visits, and physician encounters through March 2012, using multivariable negative binomial regression to compare rates of service use in the two cohorts. We analyzed data from 4987 carriers and 24,935 controls. Results Adjusted incidence rate ratios (95% CI) for service use in carriers versus controls among children < 1 year of age were: 1.11 (1.06-1.17) for ED visits; 0.97 (0.89-1.06) for inpatient hospitalization; and 1.02 (1.00-1.04) for physician encounters. Among children greater than or equai to1 year of age, adjusted rate ratios were: 1.03 (0.98-1.07) for ED visits; 1.14 (1.03-1.25) for inpatient hospitalization and 0.92 (0.90-0.94) for physician encounters. Conclusions While we identified statistically significant differences in health services use among carriers of hemoglobinopathy mutations relative to controls, effect sizes were small and directions of association inconsistent across age groups and health service types. Our findings are consistent with the assumption that carrier status is likely benign in early childhood. Keywords: Sickle cell disease, Sickle cell trait, Newborn screening, Carrier status, Health services utilization
To inform recommendations by the Canadian Task Force on Preventive Health Care on screening in primary care for the prevention and early detection of cervical cancer by systematically reviewing ...evidence of (a) effectiveness; (b) test accuracy; (c) individuals' values and preferences; and (d) strategies aimed at improving screening rates.
De novo reviews will be conducted to evaluate effectiveness and to assess values and preferences. For test accuracy and strategies to improve screening rates, we will integrate studies from existing systematic reviews with search updates to the present. Two Cochrane reviews will provide evidence of adverse pregnancy outcomes from the conservative management of cervical intraepithelial neoplasia. We will search Medline, Embase, and Cochrane Central (except for individuals' values and preferences, where Medline, Scopus, and EconLit will be searched) via peer-reviewed search strategies and the reference lists of included studies and reviews. We will search ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. Two reviewers will screen potentially eligible studies and agree on those to include. Data will be extracted by one reviewer with verification by another. Two reviewers will independently assess risk of bias and reach consensus. Where possible and suitable, we will pool studies via meta-analysis. We will compare accuracy data per outcome and per comparison using the Rutter and Gatsonis hierarchical summary receiver operating characteristic model and report relative sensitivities and specificities. Findings on values and preferences will be synthesized using a narrative synthesis approach and thematic analysis, depending on study designs. Two reviewers will appraise the certainty of evidence for all outcomes using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and come to consensus.
The publication of guidance on screening in primary care for the prevention and early detection of cervical cancer by the Task Force in 2013 focused on cytology. Since 2013, new studies using human papillomavirus tests for cervical screening have been published that will improve our understanding of screening in primary care settings. This review will inform updated recommendations based on currently available studies and address key evidence gaps noted in our previous review.
... for the suggested relation between several genetic polymorphisms and occurrence of sepsis in human beings, systematic review in 2006 of the study reports showed that the information needed to ...assess the risk of bias was lacking.3 Results of medical research need to be reported with sufficient accuracy and transparency to enable critical appraisal.
Abstract
Purpose
To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening for prostate cancer in adults aged 18 years and older in primary care. This ...protocol outlines the planned scope and methods for a series of systematic reviews.
Methods
Updates of two systematic reviews and a de novo review will be conducted to synthesize the evidence on the benefits and harms of screening for prostate cancer with a prostate-specific antigen (PSA) and/or digital rectal examination (DRE) (with or without additional information) and patient values and preferences. Outcomes for the benefits of screening include reduced prostate cancer mortality, all-cause mortality, and incidence of metastatic prostate cancer. Outcomes for the harms of screening include false-positive screening tests, overdiagnosis, complications due to biopsy, and complications of treatment including incontinence (urinary or bowel), and erectile dysfunction. The quality of life or functioning (overall and disease-specific) and psychological effects outcomes are considered as a possible benefit or harm. Outcomes for the values and preferences review include quantitative or qualitative information regarding the choice to screen or intention to undergo screening. For the reviews on benefits or harms, we will search for randomized controlled trials, quasi-randomized, and controlled studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. For the review on values and preferences, we will search for experimental or observational studies in MEDLINE, Embase, and PsycInfo. For all reviews, we will also search websites of relevant organizations, gray literature, and reference lists of included studies. Title and abstract screening, full-text review, data extraction, and risk of bias assessments will be completed independently by pairs of reviewers with any disagreements resolved by consensus or by consulting with a third reviewer. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to assess the certainty of the evidence for each outcome.
Discussion
The series of systematic reviews will be used by the Canadian Task Force on Preventive Health Care to update their 2014 guideline on screening for prostate cancer in adults aged 18 years and older.
Systematic review registration
This review has been registered with PROSPERO (CRD42022314407) and is available on the Open Science Framework (osf.io/dm32k).
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