Sequential Data-Mining for Adverse Events After Recombinant Herpes Zoster Vaccination Using the Tree-Based Scan Statistic.

Tree-based scan statistics have been successfully used to study the safety of several vaccines without prespecifying health outcomes of concern. In this study, the binomial tree-based scan statistic was applied sequentially to detect adverse events in days 1-28 compared with days 29-56 after recombinant herpes zoster (RZV) vaccination, with 5 looks at the data and formal adjustment for the repeated analyses over time. IBM MarketScan data on commercially insured persons ≥50 years of age receiving RZV during January 1, 2018, to May 5, 2020, were used. With 999,876 doses of RZV included, statistically significant signals were detected only for unspecified adverse effects/complications following immunization, with attributable risks as low as 2 excess cases per 100,000 vaccinations. Ninety percent of cases in the signals occurred in the week after vaccination and, based on previous studies, likely represent nonserious events like fever, fatigue, and headache. Strengths of our study include its untargeted nature, self-controlled design, and formal adjustment for repeated testing. Although the method requires prespecification of the risk window of interest and may miss some true signals detectable using the tree-temporal variant of the method, it allows for early detection of potential safety problems through early initiation of ongoing monitoring.

Future Research by the Australian Chiropractic Profession: Analysis of Comments and Suggestions From a Nationwide Survey of Academics and Practitioners.

OBJECTIVE: The purpose of this study was to identify and compare the research priorities of Australian practicing chiropractors and academics across listed research domains and to seek their views on existing chiropractic research strategies. Concurrent objectives were to gain insight into the perspectives on characteristics of research and solicit ideas and suggestions for future research from both groups. METHODS: This study used a mixed-method research design to collect data using an online survey portal. Australian chiropractic academics (n = 220) and practicing chiropractors who were also members of a nationally representative, practice-based research network database (n = 1680) were invited to participate. Data were collected (February 19, 2019, to May 24, 2019). The free-text data were analyzed primarily via semantic coding and verbatim referential units in cases where the category was an exact match for the textual data. Content analyses of the qualitative data were presented in a tabulated and narrative manner as identified domains. Selected representative examples were provided verbatim. RESULTS: The response rate for the survey was 44% for full-time equivalent academics, 8% for casuals and part-time chiropractic academics, and 21.5% for Australian Chiropractic Research Network database chiropractic practitioners. Open-text data comprised a narrower focus on musculoskeletal (MSK) conditions and opposition or reservations by academics and some practitioners toward the research agenda of those espousing traditional concepts and terminology. Comments from both groups illustrate the strongly held views that characterize divergent factions of the chiropractic profession. Some practitioners were highly critical of the narrow focus and epistemological paradigm of Australian university-based research, while others were strongly supportive of the traditional focus of the Australian Spinal Research Foundation. Australian academics at the 4 university-based programs held the view that MSK and spinal pain, for which some evidence already exists, should be the priority of future research, building on what is known. Practitioners believed that future research should be directed toward expanded areas such as basic science, younger populations, and non-MSK conditions. Respondents were sharply divided on attitudes toward traditional chiropractic terminology, concepts, and philosophy and the utility of future research on these topics. CONCLUSION: Our qualitative findings suggest there is a division in the Australian chiropractic profession regarding research direction and priorities. This divide exists between academics and researchers and within field practitioners. This study highlights the attitudes, opinions, and perceptions of important stakeholder groups, which should be considered by decision-makers when formulating research policy, strategy, and prioritization of funding.

A Broad Safety Assessment of the Recombinant Herpes Zoster Vaccine.

The recombinant herpes zoster vaccine (RZV), approved as a 2-dose series in the United States in October 2017, has proven highly effective and generally safe. However, a small risk of Guillain-Barré syndrome after vaccination was identified after approval, and questions remain about other possible adverse events. This data-mining study assessed RZV safety in the United States using the self-controlled tree-temporal scan statistic, scanning data on thousands of diagnoses recorded during follow-up to detect any statistically unusual temporal clustering of cases within a large hierarchy of diagnoses. IBM MarketScan data on commercially insured persons at least 50 years of age receiving RZV between January 1, 2018, and May 5, 2020, were used, including 56 days of follow-up; 1,014,329 doses were included. Statistically significant clustering was found within a few days of vaccination for unspecified adverse effects, complications, or reactions to immunization or other medical substances/care; fever; unspecified allergy; syncope/collapse; cellulitis; myalgia; and dizziness/giddiness. These findings are consistent with the known safety profile of this and other injected vaccines. No cluster of Guillain-Barré syndrome was detected, possibly due to insufficient sample size. This signal-detection method has now been applied to 5 vaccines, with consistently plausible results, and seems a promising addition to vaccine-safety evaluation methods.

Dental caries and depression in pregnant women: The role of oral health self-perception as mediator.

OBJECTIVE: This study investigated the role of oral health self-perception as mediator of association between dental caries and depression among pregnant women from the 2015 Pelotas Birth Cohort Study, Brazil. MATERIALS AND METHODS: Overall, 2,496 pregnant women participated of this oral health sub-study. Data related to demographic and socioeconomic conditions, lifetime and current depression, and oral health self-perception were collected. Participants were also assessed for dental caries (DMF-T index). Depression was assessed using the Edinburgh Postnatal Depression Scale. For analysis, six outcomes related to dental caries experience were considered. Causal mediation analysis was performed using parametric regression models. RESULTS: When it was assumed that all subjects had poor perception about oral health, it was observed that the presence of moderate/severe depressive signals and symptoms was higher in subjects with dental caries experience (OR 1.13; CI 95% 1.06-1.20), with severity of untreated dental caries (OR 2.08; CI 95% 1.16-3.78), untreated dental caries (OR 1.18; 95% CI 1.07-1.29), tooth loss (OR 1.08; 95% CI 1.02-1.14), and filled tooth (OR 1.07; 95% CI 1.02-1.16). CONCLUSIONS: Our findings show the effect of dental caries on depression is mediated by self-perception about oral health in pregnant women.

Seasonality of SARS-CoV-2 Infections in G20 Countries: Ecological Analysis of Publicly Available Data.

Previous laboratory studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed that the stability of the virus in the air or on surfaces is sensitive to seasonally relevant environmental conditions. However, the seasonality of the virus in the real world remains unclear because each country adopted various infection control policies. Therefore, we investigated peak dates with regard to new confirmed cases of coronavirus disease 2019 (COVID-19) and an association of these dates with the timing of the lockdown among G20 countries that have four seasons from 1 June 2020 to 18 February 2021. As a result, countries in both hemispheres experienced seasonal peaks in the number of COVID-19 cases both in the middle of warm and cold seasons. In addition, there were no apparent relationships between the peak date and periods with stringent measures. Our study demonstrated that SARS-CoV-2 causes seasonal outbreaks in the winter and possibly summer and thus, countries might need to consider measures to prepare for resurgence of the virus in the middle of 2021.

The effect of the Affordable Care Act dependent coverage provision on HPV vaccine uptake in young adult women, National Health and Nutrition Examination Survey 2007-2016.

The human papillomavirus (HPV) vaccine protects against cancers caused by HPV. The study objective was to examine the effect of the Affordable Care Act (ACA) dependent child coverage provision on HPV vaccination initiation, HPV vaccine completion, HPV infection, and health insurance coverage among young women. Using cross-sectional data from the National Health and Nutrition Examination Survey (NHANES), 2172 female participants were included. The impact of the dependent coverage provision on the four outcomes was examined using difference-in-difference analyses with linear probability regressions, controlling for race/ethnicity, age, income, head of household education, and family employment. ACA exposure group was operationalized by age, with those targeted by the dependent coverage provision (ages 19-25) serving as the intervention group and those similar in age but not targeted (ages 18 and 26) serving as the control group. From 2007 to 2016, HPV vaccine initiation, HPV vaccine completion, and health insurance prevalence increased and HPV infection prevalence decreased. In the difference-in-difference adjusted models, ACA exposure was not associated with HPV vaccine initiation (0.045 percentage points [95% CI -0.087, 0.178]), completion (-0.044 percentage points [95% CI -0.152, 0.063]), HPV 16/18 infection (-0.051 percentage points [95% CI -0.123, 0.021]), or health insurance (0.065 percentage points [95% CI -0.032, 0.162]) among women aged 19 to 25. The dependent coverage provision may not have addressed relevant barriers to HPV vaccination. However, given that the effect of the dependent coverage provision on HPV vaccination and health insurance has been demonstrated previously, small sample size is a concern.

The accuracy of administrative health data for identifying patients with rheumatoid arthritis: a retrospective validation study using medical records in Western Australia.

The use of administrative health datasets is increasingly important for research on disease trends and outcome. The Western Australian (WA) Rheumatic Disease Epidemiological Registry contains longitudinal health data for over 10,000 patients with rheumatoid arthritis (RA). Accurate coding for RA is essential to the validity of this dataset. Investigate the diagnostic accuracy of International Classification of Diseases (ICD)-based discharge codes for RA at WA's largest tertiary hospital. Medical records for a sample of randomly selected patients with ICD-10 codes (M05.00-M06.99) in the hospital discharge database between 2008 and 2020 were retrospectively reviewed. Rheumatologist-reported diagnoses and ACR/EULAR classification criteria were used as reference standards to determine accuracy measures. Medical chart review was completed for 87 patients (mean (± SD) age 64.7 ± 17.2 years), 67.8% female). A total of 80 (91.9%) patients had specialist confirmed RA diagnosis, while seven patients (8%) had alternate clinical diagnoses. Among 87 patients, 69 patients (79.3%) were fulfilled ACR/EULAR classification criteria. The agreement between the reference standards was moderate (Kappa 0.41). Based on rheumatologist-reported diagnoses and ACR/EULAR classification criteria, primary diagnostic codes for RA alone had a sensitivity of (90% vs 89.8%), and PPV (90.9% vs 63.6%), respectively. A combination of a diagnostic RA code with biologic infusion codes in two or more codes increased the PPV to 97.9%. Hospital discharge diagnostic codes in WA identify RA patients with a high degree of accuracy. Combining a primary diagnostic code for RA with biological infusion codes can further increase the PPV.

Hospital Records of Pain, Fatigue, or Circulatory Symptoms in Girls Exposed to Human Papillomavirus Vaccination: Cohort, Self-Controlled Case Series, and Population Time Trend Studies.

Human papillomavirus (HPV) vaccination has been associated with subsequent diffuse symptoms in girls, reducing public confidence in the vaccine. We examined whether girls have nonspecific outcomes of HPV vaccination, using triangulation from cohort, self-controlled case series (SCCS), and population time trend analyses carried out in Denmark between 2000 and 2014. The study population consisted of 314,017 HPV-vaccinated girls and 314,017 age-matched HPV-unvaccinated girls (cohort analyses); 11,817 girls with hospital records (SCCS analyses); and 1,465,049 girls and boys (population time trend analyses). The main outcome measures were hospital records of pain, fatigue, or circulatory symptoms. The cohort study revealed no increased risk among HPV vaccine-exposed girls, with incidence rate ratios close to 1.0 for abdominal pain, nonspecific pain, headache, hypotension/syncope, tachycardia (including postural orthostatic tachycardia syndrome), and malaise/fatigue (including chronic fatigue syndrome). In the SCCS analyses, we observed no association between HPV vaccination and subsequent symptoms. In time trend analyses, we observed a steady increase in these hospital records in both girls and (HPV-unvaccinated) boys, with no relationship to the 2009 introduction of HPV vaccine to Denmark's vaccination program. This study, which had nationwide coverage, showed no evidence of a causal link between HPV vaccination and diffuse autonomic symptoms leading to hospital contact.

Improving design choices in Delphi studies in medicine: the case of an exemplary physician multi-round panel study with 100% response.

BACKGROUND: A proper application of the Delphi technique is essential for obtaining valid research results. Medical researchers regularly use Delphi studies, but reports often lack detailed information on methodology and controlled feedback: in the medical literature, papers focusing on Delphi methodology issues are rare. Since the introduction of electronic surveys, details on response times remain scarce. We aim to bridge a number of gaps by providing a real world example covering methodological choices and response times in detail. METHODS: The objective of our e(lectronic)-Delphi study was to determine minimum standards for emergency departments (EDs) in the Netherlands. We opted for a two-part design with explicit decision rules. Part 1 focused on gathering and defining items; Part 2 addressed the main research question using an online survey tool. A two-person consensus rule was applied throughout: even after consensus on specific items was reached, panellists could reopen the discussion as long as at least two panellists argued similarly. Per round, the number of reminders sent and individual response times were noted. We also recorded the methodological considerations and evaluations made by the research team prior to as well as during the study. RESULTS: The study was performed in eight rounds and an additional confirmation round. Response rates were 100% in all rounds, resulting in 100% consensus in Part 1 and 96% consensus in Part 2. Our decision rules proved to be stable and easily applicable. Items with negative advice required more rounds before consensus was reached. Response delays were mostly due to late starts, but once panellists started, they nearly always finished the questionnaire on the same day. Reminders often yielded rapid responses. Intra-individual differences in response time were large, but quick responders remained quick. CONCLUSIONS: We advise those considering Delphi study to follow the CREDES guideline, consider a two-part design, invest in personal commitment of the panellists, set clear decision rules, use a consistent lay-out and send out your reminders early. Adopting this overall approach may assist researchers in future Delphi studies and may help to improve the quality of Delphi designs in terms of improved rigor and higher response rates.

Using the Self-Controlled Tree-Temporal Scan Statistic to Assess the Safety of Live Attenuated Herpes Zoster Vaccine.

The self-controlled tree-temporal scan statistic allows detection of potential vaccine- or drug-associated adverse events without prespecifying the specific events or postexposure risk intervals of concern. It thus opens a promising new avenue for safety studies. The method has been successfully used to evaluate the safety of 2 vaccines for adolescents and young adults, but its suitability to study vaccines for older adults had not been established. The present study applied the method to assess the safety of live attenuated herpes zoster vaccination during 2011-2017 in US adults aged ≥60 years, using claims data from Truven Health MarketScan Research Databases. Counts of International Classification of Diseases diagnosis codes recorded in emergency department or hospital settings were scanned for any statistically unusual clustering within a hierarchical tree structure of diagnoses and within 42 days after vaccination. Among 1.24 million vaccinations, 4 clusters were found: cellulitis on days 1-3, nonspecific erythematous condition on days 2-4, "other complications . . ." on days 1-3, and nonspecific allergy on days 1-6. These results are consistent with local injection-site reactions and other known, generally mild, vaccine-associated adverse events and a favorable safety profile. This method might be useful for assessing the safety of other vaccines for older adults.

Predictors of Response Outcomes for Research Recruitment Through a Central Cancer Registry: Evidence From 17 Recruitment Efforts for Population-Based Studies.

When recruiting research participants through central cancer registries, high response fractions help ensure population-based representation. We conducted multivariable mixed-effects logistic regression to identify case and study characteristics associated with making contact with and obtaining cooperation of Utah cancer cases using data from 17 unique recruitment efforts undertaken by the Utah Cancer Registry (2007-2016) on behalf of the following studies: A Population-Based Childhood Cancer Survivors Cohort Study in Utah, Comparative Effectiveness Analysis of Surgery and Radiation for Prostate Cancer (CEASAR Study), Costs and Benefits of Follow-up Care for Adolescent and Young Adult Cancers, Study of Exome Sequencing for Head and Neck Cancer Susceptibility Genes, Genetic Epidemiology of Chronic Lymphocytic Leukemia, Impact of Remote Familial Colorectal Cancer Risk Assessment and Counseling (Family CARE Project), Massively Parallel Sequencing for Familial Colon Cancer Genes, Medullary Thyroid Carcinoma (MTC) Surveillance Study, Osteosarcoma Surveillance Study, Prostate Cancer Outcomes Study, Risk Education and Assessment for Cancer Heredity Project (REACH Project), Study of Shared Genomic Segment Analysis and Tumor Subtyping in High-Risk Breast-Cancer Gene Pedigrees, Study of Shared Genomic Segment Analysis for Localizing Multiple Myeloma Genes. Characteristics associated with lower odds of contact included Hispanic ethnicity (odds ratio (OR) = 0.34, 95% confidence interval (CI): 0.27, 0.41), nonwhite race (OR = 0.46, 95% CI: 0.35, 0.60), and younger age at contact. Years since diagnosis was inversely associated with making contact. Nonwhite race and age ≥60 years had lower odds of cooperation. Study features with lower odds of cooperation included longitudinal design (OR = 0.50, 95% CI: 0.41, 0.61) and study brochures (OR = 0.70, 95% CI: 0.54, 0.90). Increased odds of cooperation were associated with including a questionnaire (OR = 3.19, 95% CI: 1.54, 6.59), postage stamps (OR = 1.60, 95% CI: 1.21, 2.12), and incentives (OR = 1.62, 95% CI: 1.02, 2.57). Among cases not responding after the first contact, odds of eventual response were lower when >10 days elapsed before subsequent contact (OR = 0.71, 95% CI: 0.59, 0.85). Obtaining high response is challenging, but study features identified in this analysis support better results when recruiting through central cancer registries.

Associations of insulin-like growth factor-I and insulin-like growth factor binding protein-3 with bone quality in the general adult population.

OBJECTIVE: Growth hormone (GH) and its main mediator, insulin-like growth factor-I (IGF-I), play a significant role in bone metabolism. The relations between IGF-I and bone mineral density (BMD) or osteoporosis have been assessed in previous studies but whether the associations are sex-specific remains uncertain. Moreover, only a few studies examined bone quality assessed by quantitative ultrasound (QUS). We aimed to investigate these associations in the general population of north-east Germany. DESIGN AND MEASUREMENTS: Data from 1759 men and 1784 women who participated in the baseline examination of the Study of Health in Pomerania (SHIP)-Trend were used. IGF-I and IGF-binding protein-3 (IGFBP-3) concentrations were measured on the IDS-iSYS multidiscipline automated analyser (Immunodiagnostic Systems Limited). QUS measurements were performed at the heel (Achilles InSight, GE Healthcare). Sex-specific linear and multinomial logistic regression models adjusted for potential confounders were calculated. RESULTS: Linear regression analyses revealed significant positive associations between IGF-I and IGF-I/IGFBP-3 ratio, a marker for free IGF-I, with all QUS parameters in men. Among women, we found an inverse association between IGF-I and the QUS-based fracture risk but no association with any other QUS parameter. There was no association between IGFBP-3 and the QUS-based fracture risk. CONCLUSIONS: Our data suggest an important role of IGF-I on bone quality in men. The observed association of IGF-I with the QUS-based stiffness index and QUS-based fracture risk in this study might animate clinicians to refer patients with low IGF-I levels, particularly men, to a further evaluation of risk factors for osteoporosis and a detailed examination of the skeletal system.

Assessment of demographic and perinatal predictors of non-response and impact of non-response on measures of association in a population-based case control study: findings from the Georgia Study to Explore Early Development.

BACKGROUND: Participation in epidemiologic studies has declined, raising concerns about selection bias. While estimates derived from epidemiologic studies have been shown to be robust under a wide range of scenarios, additional empiric study is needed. The Georgia Study to Explore Early Development (GA SEED), a population-based case-control study of risk factors for autism spectrum disorder (ASD), provided an opportunity to explore factors associated with non-participation and potential impacts of non-participation on association studies. METHODS: GA SEED recruited preschool-aged children residing in metropolitan-Atlanta during 2007-2012. Children with ASD were identified from multiple schools and healthcare providers serving children with disabilities; children from the general population (POP) were randomly sampled from birth records. Recruitment was via mailed invitation letter with follow-up phone calls. Eligibility criteria included birth and current residence in study area and an English-speaking caregiver. Many children identified for potential inclusion could not be contacted. We used data from birth certificates to examine demographic and perinatal factors associated with participation in GA SEED and completion of the data collection protocol. We also compared ASD-risk factor associations for the final sample of children who completed the study with the initial sample of all likely ASD and POP children invited to potentially participate in the study, had they been eligible. Finally, we derived post-stratification sampling weights for participants who completed the study and compared weighted and unweighted associations between ASD and two factors collected via post-enrollment maternal interview: infertility and reproductive stoppage. RESULTS: Maternal age and education were independently associated with participation in the POP group. Maternal education was independently associated with participation in the ASD group. Numerous other demographic and perinatal factors were not associated with participation. Moreover, unadjusted and adjusted odds ratios for associations between ASD and several demographic and perinatal factors were similar between the final sample of study completers and the total invited sample. Odds ratios for associations between ASD and infertility and reproductive stoppage were also similar in unweighted and weighted analyses of the study completion sample. CONCLUSIONS: These findings suggest that effect estimates from SEED risk factor analyses, particularly those of non-demographic factors, are likely robust.

Online market research panel members as controls in case-control studies to investigate gastrointestinal disease outbreaks: early experiences and lessons learnt from the UK.

Established methods of recruiting population controls for case-control studies to investigate gastrointestinal disease outbreaks can be time consuming, resulting in delays in identifying the source or vehicle of infection. After an initial evaluation of using online market research panel members as controls in a case-control study to investigate a Salmonella outbreak in 2013, this method was applied in four further studies in the UK between 2014 and 2016. We used data from all five studies and interviews with members of each outbreak control team and market research panel provider to review operational issues, evaluate risk of bias in this approach and consider methods to reduce confounding and bias. The investigators of each outbreak reported likely time and cost savings from using market research controls. There were systematic differences between case and control groups in some studies but no evidence that conclusions on the likely source or vehicle of infection were incorrect. Potential selection biases introduced by using this sampling frame and the low response rate are unclear. Methods that might reduce confounding and some bias should be balanced with concerns for overmatching. Further evaluation of this approach using comparisons with traditional methods and population-based exposure survey data is recommended.

Quality of dying and quality of end-of-life care of nursing home residents in six countries: An epidemiological study.

BACKGROUND: Nursing homes are among the most common places of death in many countries. AIM: To determine the quality of dying and end-of-life care of nursing home residents in six European countries. DESIGN: Epidemiological survey in a proportionally stratified random sample of nursing homes. We identified all deaths of residents of the preceding 3-month period. Main outcomes: quality of dying in the last week of life (measured using End-of-Life in Dementia Scales - Comfort Assessment while Dying (EOLD-CAD)); quality of end-of-life care in the last month of life (measured using Quality of Dying in Long-Term Care (QoD-LTC) scale). Higher scores indicate better quality. SETTING/PARTICIPANTS: Three hundred and twenty-two nursing homes in Belgium, Finland, Italy, the Netherlands, Poland and England. Participants were staff (nurses or care assistants) most involved in each resident's care. RESULTS: Staff returned questionnaires regarding 1384 (81.6%) of 1696 deceased residents. The End-of-Life in Dementia Scales - Comfort Assessment while Dying mean score (95% confidence interval) (theoretical 14-42) ranged from 29.9 (27.6; 32.2) in Italy to 33.9 (31.5; 36.3) in England. The Quality of Dying in Long-Term Care mean score (95% confidence interval) (theoretical 11-55) ranged from 35.0 (31.8; 38.3) in Italy to 44.1 (40.7; 47.4) in England. A higher End-of-Life in Dementia Scales - Comfort Assessment while Dying score was associated with country ( p = 0.027), older age ( p = 0.012), length of stay ⩾1 year ( p = 0.034), higher functional status ( p < 0.001). A higher Quality of Dying in Long-Term Care score was associated with country ( p < 0.001), older age ( p < 0.001), length of stay ⩾1 year ( p < 0.001), higher functional status ( p = 0.002), absence of dementia ( p = 0.001), death in nursing home ( p = 0.033). CONCLUSION: The quality of dying and quality of end-of-life care in nursing homes in the countries studied are not optimal. This includes countries with high levels of palliative care development in nursing homes such as Belgium, the Netherlands and England.

An overview of confounding. Part 1: the concept and how to address it.

Confounding is an important source of bias, but it is often misunderstood. We consider how confounding occurs and how to address confounding using examples. Study results are confounded when the effect of the exposure on the outcome, mixes with the effects of other risk and protective factors for the outcome. This problem arises when these factors are present to different degrees among the exposed and unexposed study participants, but not all differences between the groups result in confounding. Thinking about an ideal study where all of the population of interest is exposed in one universe and is unexposed in a parallel universe helps to distinguish confounders from other differences. In an actual study, an observed unexposed population is chosen to stand in for the unobserved parallel universe. Differences between this substitute population and the parallel universe result in confounding. Confounding by identified factors can be addressed analytically and through study design, but only randomization has the potential to address confounding by unmeasured factors. Nevertheless, a given randomized study may still be confounded. Confounded study results can lead to incorrect conclusions about the effect of the exposure of interest on the outcome.

An overview of confounding. Part 2: how to identify it and special situations.

Confounding biases study results when the effect of the exposure on the outcome mixes with the effects of other risk and protective factors for the outcome that are present differentially by exposure status. However, not all differences between the exposed and unexposed group cause confounding. Thus, sources of confounding must be identified before they can be addressed. Confounding is absent in an ideal study where all of the population of interest is exposed in one universe and is unexposed in a parallel universe. In an actual study, an observed unexposed population represents the unobserved parallel universe. Thinking about differences between this substitute population and the unexposed parallel universe helps identify sources of confounding. These differences can then be represented in a diagram that shows how risk and protective factors for the outcome are related to the exposure. Sources of confounding identified in the diagram should be addressed analytically and through study design. However, treating all factors that differ by exposure status as confounders without considering the structure of their relation to the exposure can introduce bias. For example, conditions affected by the exposure are not confounders. There are also special types of confounding, such as time-varying confounding and unfixable confounding. It is important to evaluate carefully whether factors of interest contribute to confounding because bias can be introduced both by ignoring potential confounders and by adjusting for factors that are not confounders. The resulting bias can result in misleading conclusions about the effect of the exposure of interest on the outcome.

Prevalence and trends of overweight and obesity in older adults from 10 European countries from 2005 to 2013.

AIMS: Overweight and obesity are clinical public-health concerns worldwide. Amongst older adults, the prevalence of overweight and obesity is considered high. The purpose of this study was to provide current data regarding the prevalence and trends of overweight and obesity of adults from 2005 to 2013 in 10 European countries. METHODS: The data used in the present study were derived from the first, second, fourth and fifth waves of the Survey of Health, Ageing and Retirement in Europe. The present study includes individuals aged ⩾50 years from 10 European countries. Body mass index (BMI) was calculated from self-reported height and weight (kg/m2). RESULTS: The general prevalence of overweight (BMI ⩾25 kg/m2) was slightly above 60% and remained stable between 2005 (60.1%, 95% confidence interval (CI): 59.3-60.9%) and 2013 (60.3%, 95% CI: 59.7-60.9%). On the other hand, the prevalence of obesity (BMI ⩾30 kg/m2) increased significantly (1.6 points, 95% CI: 0.7-2.6) from 17.5% in 2005 to 19.2% in 2013. Although the prevalence of obesity increased in most countries, the only significant increase was observed in Germany (5.8 points, 95% CI: 1.8-9.9). Spain was the only country where the prevalence of obesity decreased significantly (-4.7 points, 95% CI: -8.8 to -0.5). Sex and age differences are reported. CONCLUSIONS: Although the prevalence of overweight was stable, the prevalence of obesity rose. Based on the data currently available for Europe, the prevalence of obesity in European older adults has already reached epidemic proportions, which reinforces the need for the development of effective healthy lifestyle programs.

PEER-REVIEWED JOURNAL EDITORS' VIEWS ON REAL-WORLD EVIDENCE.

OBJECTIVES: Peer-review publication is a critical step to the translation and dissemination of research results into clinical practice guidelines, health technology assessment (HTA) and payment policies, and clinical care. The objective of this study was to examine current views of journal editors regarding: (i) The value of real-world evidence (RWE) and how it compares with other types of studies; (ii) Education and/or resources journal editors provide to their peer reviewers or perceive as needed for authors, reviewers, and editors related to RWE. METHODS: Journal editors' views on the value of RWE and editorial procedures for RWE manuscripts were obtained through telephone interviews, a survey, and in-person, roundtable discussion. RESULTS: In total, seventy-nine journals were approached, resulting in fifteen telephone interviews, seventeen survey responses and eight roundtable participants. RWE was considered valuable by all interviewed editors (n = 15). Characteristics of high-quality RWE manuscripts included: novelty/relevance, rigorous methodology, and alignment of data to research question. Editors experience challenges finding peer reviewers; however, these challenges persist across all study designs. Journals generally do not provide guidance, assistance, or training for reviewers, including for RWE studies. Health policy/health services research (HSR) editors were more likely than specialty or general medicine editors to participate in this study, potentially indicating that HSR researchers are more comfortable/interested in RWE. CONCLUSIONS: Editors report favorable views of RWE studies provided studies examine important questions and are methodologically rigorous. Improving peer-review processes across all study designs, has the potential to improve the evidence base for decision making, including HTA.

Questionnaire Breakoff and Item Nonresponse in Web-Based Questionnaires: Multilevel Analysis of Person-Level and Item Design Factors in a Birth Cohort.

BACKGROUND: Web-based questionnaires are increasingly used in epidemiologic studies, as traditional methods are facing a decrease in response rates and an increase in costs. However, few studies have investigated factors related to the level of completion of internet-based epidemiologic questionnaires. OBJECTIVE: Our objective was to identify person-level characteristics and item design factors associated with breakoff (not finishing the questionnaire) and item nonresponse in a Web-based questionnaire. METHODS: This study was a cross-sectional analysis of the baseline questionnaire, applied from 2005 to 2016, of the Italian NINFEA (Nascita e Infanzia: gli Effetti dell'Ambiente) birth cohort. The baseline questionnaire was administered to enrolled women, who could register at any time during pregnancy. We used logistic regression to analyze the influence of person-level factors on questionnaire breakoff, and a logistic multilevel model (first level: items of the questionnaire; second level: sections of the questionnaire; third level: study participants) to analyze the influence of person-level and item design factors on item nonresponse. Since the number of applicable items depended on the respondent's characteristics and breakoff, we used inverse probability weighting to deal with missing by design. RESULTS: Of 5970 women, 519 (8.69%) did not finish the questionnaire. Older age (adjusted odds ratio 1.40, 95% CI 1.05-1.88), lower educational level (adjusted odds ratio [OR] 1.53, 95% CI 1.23-1.90), and earlier stage of pregnancy (adjusted OR 3.01, 95% CI 2.31-3.92) were positively associated with questionnaire breakoff. Of the 1,062,519 applicable items displayed for the participants, 22,831 were not responded to (overall prevalence of item nonresponse 2.15%). Item nonresponse was positively associated with older age (adjusted OR 1.25, 95% CI 1.14-1.38), being in the first trimester of pregnancy (adjusted OR 1.18, 95% CI 1.06-1.31), and lower educational level (adjusted OR 1.23, 95% CI 1.14-1.33). Dropdown menu items (adjusted OR 1.77, 95% CI 1.56-2.00) and items organized in grids (adjusted OR 1.69, 95% CI 1.49-1.91) were positively associated with item nonresponse. CONCLUSIONS: It is important to use targeted strategies to keep participants motivated to respond. Item nonresponse in internet-based questionnaires is affected by person-level and item design factors. Some item types should be limited to reduce item nonresponse.