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Few biomarker-based validation studies have examined error in online self-report dietary assessment instruments, and food records (FRs) have been considered less than food frequency questionnaires (FFQs) and 24-hour recalls (24HRs). We investigated measurement error in online and paper-based FFQs, online 24HRs, and paper-based FRs in 3 samples drawn primarily from 3 cohorts, comprising 1,393 women and 1,455 men aged 45–86 years. Data collection occurred from January 2011 to October 2013. Attenuation factors and correlation coefficients between reported and true usual intake for energy, protein, sodium, potassium, and respective densities were estimated using recovery biomarkers. Across studies, average attenuation factors for energy were 0.07, 0.07, and 0.19 for a single FFQ, 24HR, and FR, respectively. Correlation coefficients for energy were 0.24, 0.23, and 0.40, respectively. Excluding energy, the average attenuation factors across nutrients and studies were 0.22 for a single FFQ, 0.22 for a single 24HR, and 0.51 for a single FR. Corresponding correlation coefficients were 0.31, 0.34, and 0.53, respectively. For densities (nutrient expressed relative to energy), the average attenuation factors across studies were 0.37, 0.17, and 0.50, respectively. The findings support prior research suggesting different instruments have unique strengths that should be leveraged in epidemiologic research. [ABSTRACT FROM AUTHOR]

Background Persons with HIV and tuberculosis (TB) co-infection require transaminase monitoring while on hepatotoxic medications. A novel paper-based, point-of-care transaminase test is in development at an anticipated cost of $1 per test. Methods To project long-term clinical outcomes and estimate the cost-effectiveness of using a paper-based fingerstick test to monitor for drug-induced liver injury (DILI), as compared with automated testing and with no laboratory monitoring. The design was a decision analytic model, including deterministic and probabilistic sensitivity analyses. Data sources were observational cohorts and a validation study of the paper-based test. The target population was HIV/TB co-infected persons in South Africa on antiretroviral therapy who were initiating TB therapy. Interventions: (1) clinical (no laboratory) monitoring; (2) monitoring using the paper-based test with a ≥120 IU/mL threshold for positivity; (3) monitoring using the paper-based test with a ≥200 IU/mL threshold for positivity; (4) monitoring using the paper-based test using 1 of 3 categories: <120 IU/mL, 120 to 200 IU/mL, and >200 IU/mL (“bin placement”); (5) monitoring using automated ALT testing using the same 3 categories (“automated testing”). The outcome measures were discounted quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Results The ICER of automated testing was $5180/QALY. Use of the paper-based test with the bin placement strategy was cost-effective compared with clinical monitoring alone. Conclusion At its current performance, monthly DILI monitoring by bin placement using the paper-based test was cost-effective, compared with clinical monitoring, in HIV/TB co-infected persons in South Africa. [ABSTRACT FROM AUTHOR]

The authors assessed the utility and cost-effectiveness of using a World Wide Web-based questionnaire in a large prospective cohort study, the Black Women's Health Study (BWHS). In 1995, 59,000 African-American women were recruited into the BWHS through a paper questionnaire. Follow-up paper questionnaires have been mailed every 2 years since then. During the 2003, 2005, and 2007 questionnaire cycles, participants were given the option of completing a Web-based questionnaire. The cost of developing and processing a returned paper questionnaire was 4 times that of a returned Web questionnaire, primarily because of return postage costs and greater processing time for paper questionnaires. The proportion of respondents who completed a Web questionnaire doubled from 2003 to 2007, from 10.1% to 19.9%, but the characteristics of those completing the Web questionnaire remained the same. Web response was greatest at younger ages (20.9% of those aged <30 years) and declined with age to 3.6% among women aged 60 years or more. Web questionnaires were filled out more completely than paper questionnaires, regardless of the sensitivity of a question. The use of a Web questionnaire in the BWHS resulted in cost savings and more complete responses. Although there are advantages to using a Web questionnaire, the use of multiple means of soliciting questionnaire responses is still needed. [ABSTRACT FROM PUBLISHER]

The authors repeatedly use the construction "X% of patients who did Y at baseline" when they should have used the construction 'X% of I all i 316 patients (i.e. those who provided follow-up data)'. The omission is all the more disquieting given that the corresponding author of the paper was a lead investigator on the PACE trial itself. Dear Sir, I Occupational Medicine i recently published a paper from Stevelink I et al. i [[1]] called 'Chronic fatigue syndrome and occupational status: a retrospective longitudinal study'. [Extracted from the article]

Background Value-based healthcare (VBHC) is a conceptual framework to improve the value of healthcare by health, care-process and economic outcomes. Benchmarking should provide useful information to identify best practices and therefore a good instrument to improve quality across healthcare organizations. This paper aims to provide a proof-of-concept of the feasibility of an international VBHC benchmarking in breast cancer, with the ultimate aim of being used to share best practices with a data-driven approach among healthcare organizations from different health systems. Methods In the VOICE community—a European healthcare centre cluster intending to address VBHC from theory to practice—information on patient-reported, clinical-related, care-process-related and economic-related outcomes were collected. Patient archetypes were identified using clustering techniques and an indicator set following a modified Delphi was defined. Benchmarking was performed using regression models controlling for patient archetypes and socio-demographic characteristics. Results Six hundred and ninety patients from six healthcare centres were included. A set of 50 health, care-process and economic indicators was distilled for benchmarking. Statistically significant differences across sites have been found in most health outcomes, half of the care-process indicators, and all economic indicators, allowing for identifying the best and worst performers. Conclusions To the best of our knowledge, this is the first international experience providing evidence to be used with VBHC benchmarking intention. Differences in indicators across healthcare centres should be used to identify best practices and improve healthcare quality following further research. Applied methods might help to move forward with VBHC benchmarking in other medical conditions. [ABSTRACT FROM AUTHOR]

Objectives This scoping review identifies research in musculoskeletal disorders that uses high frequency follow-up of symptoms. The aim was to investigate whether symptom variability is investigated as a predictor of disease outcome and how intensive follow-up methods are used in musculoskeletal research. Methods Embase, MEDLINE and PsycInfo were searched using OVID, and the Institute of Electrical and Electronic Engineers was also searched using the Institute of Electrical and Electronic Engineers Xplore search engine. Studies were systematically reviewed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses, but no meta-analysis was done because the priority in this study is to identify gaps in available literature. Results Twenty-one papers were included. There was a mean of 54 patients per study (s. d. of 27.7). Two-thirds of the papers looked at how a symptom influences another in the short-term (subsequent assessment in the same day or next day), but none looked at the long-term. Only one study considered symptom variability investigating how higher variability in pain (defined by the s. d.) is associated with higher average pain severity and lower average sleep quality. Conclusion The methodology of musculoskeletal disorder research has changed from completing paper booklets to using electronic data capture (smartphones). There has also been a trend of collecting more intensive longitudinal data, but very little research utilizes these data to look at how symptom variability affects symptom outcomes. This demonstrates a gap in research where furthering understanding of this will help clinicians decide on the most important symptom to address in future patients. [ABSTRACT FROM AUTHOR]

Most epidemiological studies examine how risk factors relate to average difference in outcomes (linear regression) or odds of a binary outcome (logistic regression); they do not explicitly examine whether risk factors are associated differentially across the distribution of the health outcome investigated. This paper documents a phenomenon found repeatedly in the minority of epidemiological studies which do this (via quantile regression): associations between a range of established risk factors and body mass index (BMI) are progressively stronger in the upper ends of the BMI distribution. In this paper, we document this finding and provide illustrative evidence of it in the 1958 British birth cohort study. Associations of low childhood socio-economic position, high maternal weight, low childhood general cognition and adult physical inactivity with higher BMI are larger at the upper end of the BMI distribution, on both absolute and relative scales. For example, effect estimates for socio-economic position and childhood cognition were around three times larger at the 90th compared with 10th quantile, while effect estimates for physical inactivity were increasingly larger from the 50th to 90th quantiles, yet null at lower quantiles. We provide potential explanations for these findings and discuss implications. Risk factors may have larger causal effects among those in worse health, and these effects may not be discovered when health is only examined in average terms. In such scenarios, population-based approaches to intervention may have larger benefits than anticipated when assuming equivalent benefit across the population. Further research is needed to understand why effect estimates differ across the BMI outcome distribution and to investigate whether differential effects exist for other physical and mental health outcomes. [ABSTRACT FROM AUTHOR]

Background: Dentists and dental students have been reported to be at high risk of burnout and risk factors have been identified. Despite research into burnout in dentists, only a few papers have identified significantly associated factors. Aims: To identify the most significant factors associated with burnout in dentists and dental students in published literature. Methods: We systematically searched MEDLINE, EMBASE and HMIC electronic databases to source literature on the factors associated with burnout in dentists. We critically appraised and themed papers using the Critical Appraisal Skills Programme to find the most significant factors. Results: From 115 studies identified by the search string, we deemed 33 papers to be relevant for review. The most prevalent and significant factors associated with burnout were: younger age, male gender, student status, high job-strain/working hours, those enrolled in clinical degree programmes and certain personality types. However, only a limited amount of literature explored the directional relationship between these factors and burnout. Conclusions: This review identified several significant factors contributing to burnout in dentists and dental students. Further longitudinal and prospective studies are required to assess causation. Burnout should be considered a multifactorial phenomenon that can develop early in a dental career. Screening programmes and coping strategies might help to identify and prevent it. [ABSTRACT FROM AUTHOR]

Qualitative research methods, while rising in popularity, are still a relatively underutilized tool in public health research. Usually reserved for small samples, qualitative research techniques have the potential to enhance insights gained from large questionnaires and cohort studies, both deepening the interpretation of quantitative data and generating novel hypotheses that might otherwise be missed by standard approaches; this is especially true where exposures and outcomes are new, understudied, or rapidly changing, as in a pandemic. However, methods for the conduct of qualitative research within large samples are underdeveloped. Here, we describe a novel method of applying qualitative research methods to free-text comments collected in a large epidemiologic questionnaire. Specifically, this method includes: 1) a hierarchical system of coding through content analysis; 2) a qualitative data management application; and 3) an adaptation of Cohen's κ and percent agreement statistics for use by a team of coders, applying multiple codes per record from a large codebook. The methods outlined in this paper may help direct future applications of qualitative and mixed methods within large cohort studies. [ABSTRACT FROM AUTHOR]

In longitudinal studies variables are measured repeatedly over time, leading to clustered and correlated observations. If the goal of the study is to develop prediction models, machine learning approaches such as the powerful random forest (RF) are often promising alternatives to standard statistical methods, especially in the context of high-dimensional data. In this paper, we review extensions of the standard RF method for the purpose of longitudinal data analysis. Extension methods are categorized according to the data structures for which they are designed. We consider both univariate and multivariate response longitudinal data and further categorize the repeated measurements according to whether the time effect is relevant. Even though most extensions are proposed for low-dimensional data, some can be applied to high-dimensional data. Information of available software implementations of the reviewed extensions is also given. We conclude with discussions on the limitations of our review and some future research directions. [ABSTRACT FROM AUTHOR]

Background: Rigorously designed longitudinal studies can inform how best to reduce the widening health gap between Indigenous and non-Indigenous children.Methods: A systematic review was performed to identify and present the breadth and depth of longitudinal studies reporting the health and well-being of Indigenous children (aged 0-18 years) globally. Databases were searched up to 23 June 2020. Study characteristics were mapped according to domains of the life course model of health. Risk of bias was assessed using the National Institutes of Health (NIH) Study Quality Assessment Tools. Reported level of Indigenous involvement was also appraised; PROSPERO registration CRD42018089950.Results: From 5545 citations, 380 eligible papers were included for analysis, representing 210 individual studies. Of these, 41% were located in Australia (n = 88), 22.8% in the USA (n = 42), 11.9% in Canada (n = 25) and 10.9% in New Zealand (n = 23). Research tended to focus on either health outcomes (50.9%) or health-risk exposures (43.8%); 55% of studies were graded as 'good' quality; and 89% of studies made at least one reference to the involvement of Indigenous peoples over the course of their research.Conclusions: We identified gaps in the longitudinal assessment of cultural factors influencing Indigenous child health at the macrosocial level, including connection to culture and country, intergenerational trauma, and racism or discrimination. Future longitudinal research needs to be conducted with strong Indigenous leadership and participation including holistic concepts of health. This is critical if we are to better understand the systematic factors driving health inequities experienced by Indigenous children globally. [ABSTRACT FROM AUTHOR]

The use of clinical neuropsychological tests in the evaluation of National Football League (NFL) players has been ongoing for more than two decades. Prior research has demonstrated that the NFL population may perform differently than the general population on standard paper and pencil neuropsychological tests. Given the increased interest in the longitudinal and long-term assessment of neurocognitive functioning in this group of athletes, we reviewed the published neuropsychological literature in an attempt to compile an initial compendium of available normative data on paper and pencil as well as computerized neuropsychological tests for this group of football players. Thirteen published studies met the inclusion criteria, and the results are presented by athlete status (active vs. retired) and classified by neuropsychological domain. Suggestions for potential core batteries with this population are discussed, as are directions for future research. [ABSTRACT FROM PUBLISHER]

Background Glioblastoma (GBM) has a poor prognosis, and patients with epidermal growth factor receptor (EGFR) amplification have an even worse prognosis. Nimotuzumab is an EGFR monoclonal antibody thought to play a significant role in the treatment of GBM. This paper presents a retrospective cohort study that evaluates the clinical efficacy and safety of nimotuzumab in GBM. Materials and Methods A total of 56 newly diagnosed patients with EGFR-positive GBM were included in our study. The patients were divided into radiotherapy (RT) + temozolomide (TMZ) + nimotuzumab (39 patients) and RT + TMZ (17 patients) groups based on whether or not nimotuzumab was added during RT. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed. Results The median follow-up time was 27.9 months (95% confidence interval [CI], 25.1-30.8). The median PFS was 12.4 months (95% CI, 7.8-17.0) and 8.2 months (95% CI, 6.1-10.3) in the 2 groups, respectively, P  = .052. The median OS was 27.3 months (95% CI, 19.0-35.6) and 16.7 months (95% CI, 11.1-22.2), respectively, P   =  .018. In patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter, the PFS and OS were significantly better in patients treated with nimotuzumab than in those without nimotuzumab (median PFS: 19.3 vs 6.7 months, P   =  .001; median OS: 20.2 vs 13.8 months, P   =  .026). During the treatment period, no statistically significant difference in toxicity was noted between the 2 groups. Conclusion Our retrospective cohort study suggests the efficacy of Nimotuzumab combined with concurrent RT with TMZ in patients with newly diagnosed EGFR-positive GBM, and specifically those with unmethylated MGMT promoter. Further prospective studies are warranted to validate our findings. Besides, nimotuzumab demonstrated good safety and tolerability. [ABSTRACT FROM AUTHOR]

We tested if we could replicate the main effect relations of elevated striatum and lateral orbitofrontal cortex (OFC) response to high-calorie food stimuli to weight gain reported in past papers in six prospective datasets that used similar functional MRI (fMRI) paradigms. Participants in Study 1 (N  = 37; M (mean) age = 15.5), Study 2 (N  = 160; M age = 15.3), Study 3 (N  = 130; M age = 15.0), Study 4 (N  = 175; M age = 14.3), Study 5 (N  = 45; M age = 20.8) and Study 6 (N  = 49; M age = 31.1) completed fMRI scans at the baseline and had their body mass index (BMI) and body fat (Studies 4 and 6 only) measured at the baseline and over follow-ups. Elevated striatal response to palatable food images predicted BMI gain in Studies 1 and 6 and body fat gain in Study 6. Lateral OFC activation did not predict weight gain in any of the six studies. The result provide limited support for the hypothesis that elevated reward region responsivity to palatable food images predicts weight gain. Factors that make replication difficult are discussed and potential solutions considered. [ABSTRACT FROM AUTHOR]

The disease risk score (DRS) is a summary score that is a function of a potentially large set of covariates. The DRS can be used to control for confounding by the covariates that went into estimation of the DRS and obtain a standardized estimate of an exposure's effect on disease. However, to date, literature on the DRS has not addressed analyses that focus on estimation of survival or hazard functions, which are common in epidemiologic analyses of cohort data. Here, we propose a method for standardization of hazard ratios using the DRS in longitudinal analyses of the association between a binary exposure and an outcome. This approach to handling a potentially large set of covariates through a model-based approach to standardization may provide a useful tool for cohort analyses of hazard ratios and may be particularly well-suited to settings where an exposure propensity score is difficult to model. Simulations are used in this paper to illustrate the approach, and an empirical example is provided. [ABSTRACT FROM AUTHOR]

Good data curation is integral to cohort studies, but it is not always done to a level necessary to ensure the longevity of the data a study holds. In this opinion paper, we introduce the concept of data curation debt-the data curation equivalent to the software engineering principle of technical debt. Using the context of UK cohort studies, we define data curation debt-describing examples and their potential impact. We highlight that accruing this debt can make it more difficult to use the data in the future. Additionally, the long-running nature of cohort studies means that interest is accrued on this debt and compounded over time-increasing the impact a debt could have on a study and its stakeholders. Primary causes of data curation debt are discussed across three categories: longevity of hardware, software and data formats; funding; and skills shortages. Based on cross-domain best practice, strategies to reduce the debt and preventive measures are proposed-with importance given to the recognition and transparent reporting of data curation debt. Describing the debt in this way, we encapsulate a multi-faceted issue in simple terms understandable by all cohort study stakeholders. Data curation debt is not only confined to the UK, but is an issue the international community must be aware of and address. This paper aims to stimulate a discussion between cohort studies and their stakeholders on how to address the issue of data curation debt. If data curation debt is left unchecked it could become impossible to use highly valued cohort study data, and ultimately represents an existential risk to studies themselves. [ABSTRACT FROM AUTHOR]

Background Few studies into chronic fatigue syndrome (CFS) have emphasized work-related consequences, including return to work after illness. Aims This paper explores socio-demographic, work and clinical characteristics that are associated with occupational status among patients who were assessed at baseline and a follow-up point. Methods Longitudinal data were assessed from patients affected by CFS who attended an outpatient CFS treatment service between 2007 and 2014. Employment status at baseline and follow-up was available for 316 patients. Data were also included on gender, age, duration of CFS, fatigue severity, type and number of treatment sessions, coping strategies, functional impairment, common mental disorders and physical functioning. Results Most patients were female (73%) and had been affected by CFS for longer than 2 years (66%). Patients were followed up for an average of 285 days and over this period 53% of patients who were working remained in employment. Of the patients who were not working at baseline, 9% had returned to work at follow-up. However, of those working at baseline, 6% were unable to continue to work at follow-up. Age, fatigue severity, functional impairment, cognitive and behavioural responses, and depressive symptoms impacted on a patients' work status at follow-up. Conclusions The findings indicated that it is possible for people with CFS to remain in work or return to work, despite having had a disabling illness. Work-related outcomes should be targeted in all people of working age. [ABSTRACT FROM AUTHOR]

The acquired immune deficiency syndrome (AIDS) epidemic was first recognized in 1981, and it quickly became a public health emergency. In a 1987 paper in the American Journal of Epidemiology (Am J Epidemiol. 1987;126(2): 310-318), Richard Kaslow et al. described the launch of the Multicenter AIDS Cohort Study (MACS), a cohort study of homosexual men in 4 US cities, the purpose of which was to better understand the natural history of AIDS and its determinants. The MACS enrolled participants through a range of community contacts. These efforts facilitated rapid recruitment, but given the targeted approaches, participants tended to comprise high-risk social networks. At baseline, 4%-26% of participants at the 4 sites reported having a sexual partner who had developed AIDS. Kaslow et al. also described baseline testing for the causative agent of AIDS, the human immunodeficiency virus (HIV). HIV sero- prevalence was remarkably high, ranging from 11 %-26% across age groups in Pittsburgh to 38%-53% in Los Angeles. The major turning point in the epidemic occurred in 1995-1996 when combination antiretroviral therapy was introduced, effectively blocking HIV replication and markedly reducing AIDS morbidity and mortality. The MACS cohort continues to be followed actively 3 decades after its launch and has proven to be an important resource for information on HIV infection and AIDS. [ABSTRACT FROM AUTHOR]

Background vaccination uptake in the UK and increased care home testing are likely affecting care home visitation. With scant scientific evidence to date, the aim of this longitudinal qualitative study was to explore the impact of both (vaccination and testing) on the conduct and experiences of care home visits. Methods family carers of care home residents with dementia and care home staff from across the UK took part in baseline (October/November 2020) and follow-up interviews (March 2021). Public advisers were involved in all elements of the research. Data were analysed using thematic analysis. Results across 62 baseline and follow-up interviews with family carers (n  = 26; 11) and care home staff (n  = 16; 9), five core themes were developed: delayed and inconsistent offers of face-to-face visits; procedures and facilitation of visits; variable uptake of the COVID-19 vaccine; misinformation, education and free choice; frustration and anger among family carers. The variable uptake in staff, compared to family carers, was a key factor seemingly influencing visitation, with a lack of clear guidance leading care homes to implement infection control measures and visitation rights differently. Conclusions we make five recommendations in this paper to enable improved care home visitation in the ongoing, and in future, pandemics. Visits need to be enabled and any changes to visiting rights must be used as a last resort, reviewed regularly in consultation with residents and carers and restored as soon as possible as a top priority, whilst more education needs to be provided surrounding vaccination for care home staff. [ABSTRACT FROM AUTHOR]

Since the early 2000s, Chinese government has sought to encourage the growth of private health insurance (PHI) while simultaneously expanding the breadth of coverage in its social health insurance (SHI) system. This paper examines how the prevalence of PHI has changed during this period and the extent to which PHI contributed to the growth of horizontal and geographical inequities with a focus on healthcare utilization. National data from China Health and Nutrition Survey between 2000 and 2015 were analysed using a multilevel modelling approach. The analysis investigated the impact of SHI membership as related to PHI uptake, PHI enrolees' utilization of health services and out-of-pocket (OOP) expenses. This study found being covered by an SHI scheme reduced the uptake of PHI between 2004 and 2015. Having PHI caused an increase in utilizing outpatient care but did not affect OOP expenses. Coverage prevalence of PHI in a residential community was positively associated with the average level of healthcare utilization. Coverage prevalence of PHI and its effects on healthcare utilization varied geographically. The findings suggest that expanding the role of PHI was not effective without clear support from government policy. Furthermore, the expansion of PHI may cause an increase in horizontal and geographical inequities in healthcare utilization. [ABSTRACT FROM AUTHOR]

Background: measures of physical capability may be predictive of subsequent health, but existing published studies have not been systematically reviewed. We hypothesised that weaker grip strength, slower walking speed and chair rising and shorter standing balance time, in community-dwelling populations, would be associated with higher subsequent risk of fracture, cognitive outcomes, cardiovascular disease, hospitalisation and institutionalisation.Methods: studies were identified through systematic searches of the electronic databases MEDLINE and EMBASE (to May 2009). Reference lists of eligible papers were also manually searched.Results: twenty-four papers had examined the associations between at least one physical capability measure and one of the outcomes. As the physical capability measures and outcomes had been assessed and categorised in different ways in different studies, and there were differences in the potential confounding factors taken into account, this made it impossible to pool results. There were more studies examining fractures than other outcomes, and grip strength and walking speed were the most commonly examined capability measures. Most studies found that weaker grip strength and slower walking speed were associated with increased risk of future fractures and cognitive decline, but residual confounding may explain results in some studies. Associations between physical capability levels and the other specified outcomes have not been tested widely.Conclusions: there is some evidence to suggest that objective measures of physical capability may be predictors of subsequent health in older community-dwelling populations. Most hypothesised associations have not been studied sufficiently to draw definitive conclusions suggesting the need for further research. [ABSTRACT FROM AUTHOR]

Background Delays in diagnosing herpes simplex encephalitis (HSE) are associated with increased morbidity and mortality. The purpose of this paper is to determine the frequency and duration of diagnostic delays for HSE and risk factors for diagnostic delays. Methods Using data from the IBM Marketscan Databases, 2001–2017, we performed a retrospective cohort study of patients with HSE. We estimated the number of visits with HSE-related symptoms before diagnosis that would be expected to occur in the absence of delays and compared this estimate to the observed pattern of visits. Next, we used a simulation-based approach to compute the number of visits representing a delay, the number of missed diagnostic opportunities per case patient, and the duration of delays. We also investigated potential risk factors for delays. Results We identified 2667 patients diagnosed with HSE. We estimated 45.9% (95% confidence interval [CI], 43.6%–48.1%) of patients experienced at least 1 missed opportunity; 21.9% (95% CI, 17.3%–26.3%) of these patients had delays lasting >7 days. Risk factors for delays included being seen only in the emergency department, age <65, or a history of sinusitis or schizophrenia. Conclusions Many patients with HSE experience multiple missed diagnostic opportunities before diagnosis. [ABSTRACT FROM AUTHOR]

The collection of a subset of CFS/ME patient data as part of the.national CFS/ME collaborative was confirmed to be service evaluation by the North Somerset & Bristol Research Ethics Committee under REC reference 07/Q2006/48, and in a letter dated 29 January 2007 the Chair of the Research Ethics Committee had previously confirmed (a) that it would not be necessary to apply for ethical permission to use the data being collected as part of service evaluation for the national CFS/ME collaborative and (b) that if in future this data were to be used as part of a research project, this would be agreeable. The "Ethical Approval" section of this paper has been updated to read The data used in this study was originally collected and collated in the National Outcomes Database for the purposes of evaluation of CFS/ME services. [Extracted from the article]

In 2019, the National Institutes of Health combined the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS) into the MACS/WIHS Combined Cohort Study (MWCCS). In this paper, participants who made a study visit during October 2018–September 2019 (targeted for MWCCS enrollment) are described by human immunodeficiency virus (HIV) serostatus and compared with people living with HIV (PLWH) in the United States. Participants include 2,115 women and 1,901 men with a median age of 56 years (interquartile range, 48–63); 62% are PLWH. Study sites encompass the South (18%), the Mid-Atlantic/Northeast (45%), the West Coast (22%), and the Midwest (15%). Participant race/ethnicity approximates that of PLWH throughout the United States. Longitudinal data and specimens collected for 35 years (men) and 25 years (women) were combined. Differences in data collection and coding were reviewed, and key risk factor and comorbidity data were harmonized. For example, recent use of alcohol (62%) and tobacco (28%) are common, as are dyslipidemia (64%), hypertension (56%), obesity (42%), mildly or severely impaired daily activities (31%), depressive symptoms (28%), and diabetes (22%). The MWCCS repository includes serum, plasma, peripheral blood mononuclear cells, cell pellets, urine, cervicovaginal lavage samples, oral samples, B-cell lines, stool, and semen specimens. Demographic differences between the MACS and WIHS can confound analyses by sex. The merged MWCCS is both an ongoing observational cohort study and a valuable resource for harmonized longitudinal data and specimens for HIV-related research. [ABSTRACT FROM AUTHOR]

Background dementia policy suggests diagnosing dementia early can reduce the risk of potentially harmful hospital admissions or emergency department (ED) attendances; however, there is little evidence to support this. A diagnosis of mild cognitive impairment (MCI) before dementia is a helpful proxy to explore early diagnosis. This study investigated the association between an early diagnosis of dementia and subsequent hospitalisations and ED attendances. Method a retrospective cohort study of electronic health care records from 15,836 patients from a large secondary care database in South London, UK. Participants were divided into two groups: those with a diagnosis of MCI before dementia, an early diagnosis, and those without. Cox regression models were used to compare the risk of hospitalisation and ED attendance after dementia diagnosis and negative binomial regression models were used to compare the average length of stay and average number of ED attendances. Results participants with an early diagnosis were more likely to attend ED after their diagnosis of dementia (HR = 1.09, CI = 1.00–1.18); however, there was no difference in the number of ED attendances (IRR = 1.04, CI = 0.95–1.13). There was no difference in the risk of hospitalisation (HR = 0.99, CI = 0.91–1.08) or length of stay between the groups (IRR = 0.97, CI = 0.85–1.12). Conclusion the findings of this study do not support the assumption that an early diagnosis reduces the risk of hospitalisation or ED attendance. The patterns of health service use in this paper could reflect help-seeking behaviour before diagnosis or levels of co-morbidity. [ABSTRACT FROM AUTHOR]

Objectives The purpose of this paper is to investigate the utilisation of general practice Medicare Benefit Schedule (MBS) services aligned to Comprehensive Geriatric Assessment (CGA) within 6 months of an aged care eligibility assessment and its effects on mortality and transition to permanent residential aged care (PRAC). Design Retrospective cohort study from the Historical Cohort of the Registry of Senior Australians. Setting Community. Participants In total, 69,171 Individuals (aged 75+) receiving home care packages (HCPs) between 2011 and 2015. Outcome measures Mortality and transition to PRAC. Results The claims for a management plan with team care arrangement (TCA) within 3 months of the health assessment (i.e. CGA) was present in 5% and associated with 14% lower mortality (adjusted hazard ratio [aHR], 95%CI = 0.86, 0.80–0.93) compared to no claims, lower than that seen with partial CGA which was either health assessment claims only 7.0% (aHR, 95%CI = 0.93, 0.89–0.97) or management plan coupled with TCA claims only 9.0% (aHR, 95%CI = 0.91, 0.89–0.97). This pattern was seen in those frailer but not in those where the frailty index score was <0.21. Claims for management plans coupled with TCAs alone were associated with a 10% lower transition to PRAC (asHR, 95%CI = 0.90, 0.85–0.96) in those with FI score < 0.21 while this estimate was not significant in individuals with FI score ≥ 0.21. Conclusion It appears the conduct of a combination of interventions considered to be components of the CGA by GPs was associated with a lower risk of mortality that no claims or partial conduct of CGA. [ABSTRACT FROM AUTHOR]

Researchers increasingly wish to test hypotheses concerning the impact of environmental or disease exposures on telomere length (TL), and they use longitudinal study designs to do so. In population studies, TL is usually measured with a quantitative polymerase chain reaction (qPCR)-based method. This method has been validated by calculating its correlation with a gold standard method such as Southern blotting (SB) in cross-sectional data sets. However, in a cross-section, the range of true variation in TL is large, and measurement error is introduced only once. In a longitudinal study, the target variation of interest is small, and measurement error is introduced at both baseline and follow-up. In this paper, we present results from a small data set (n  = 20) in which leukocyte TL was measured twice 6.6 years apart by means of both qPCR and SB. The cross-sectional correlations between qPCR and SB were high at both baseline (r  = 0.90) and follow-up (r  = 0.85), yet their correlation for TL change was poor (r  = 0.48). Moreover, the qPCR data but not the SB data showed strong signatures of measurement error. Through simulation, we show that the statistical power gain from performing a longitudinal analysis is much greater for SB than for qPCR. We discuss implications for optimal study design and analysis. [ABSTRACT FROM AUTHOR]

Medication use is often underreported in paper-based questionnaires or interviews.Web-based questionnaires may improve recall ofmedication use, but data on their validity are currently lacking. Participants in the Pregnancy and Infant Development (PRIDE) Study (2014-2016; n = 557) and the Pregnancy Drug Registry (pREGnant) (2015-2016; n = 169) completed a 6-week paper-based medication diary during gestational weeks 19-24 or 26-31. In week 34, they completed a Web-based questionnaire with questions on medication names, time period and frequency of use, and quantity taken. To assess the degree of underreporting, we calculated the questionnaire's sensitivity using the medication diary as the reference standard. Sensitivity was high formany medication groups, including antiepilepticmedication (sensitivity (Sn) = 0.96, 95% confidence interval (CI): 0.89, 1.00), antacids (Sn = 0.89, 95% CI: 0.86, 0.93), and iron preparations (Sn = 0.81, 95% CI: 0.64, 0.98). However, medications for short-term use were underreported more frequently, with sensitivities of 0.54 (95% CI: 0.35, 0.72) for antihistamines, 0.63 (95% CI: 0.57, 0.69) for analgesic and antipyretic agents, and 0.57 (95% CI: 0.51, 0.64) for acetaminophen. Shortening the period of time between exposure and questionnaire administration increased sensitivity substantially. In conclusion, underreporting in Web-based questionnaires is limited for many medication groups. In prospective studies, underreporting of medications for short-term usemay be reduced by decreasing the interval between consecutive questionnaires. medication use; pregnancy; Pregnancy Drug Registry (pREGnant); Pregnancy and Infant Development (PRIDE) [ABSTRACT FROM AUTHOR]

Study Question: Is bacterial vaginosis (BV) associated with fecundability?Summary Answer: Women with BV may be at increased risk for sub-fecundity.What Is Known Already: While BV has been associated with poor IVF outcomes, the association between vaginal microbiota disruption and non-medically assisted conception has not been thoroughly explored.Study Design, Size, Duration: Kenyan women with fertility intent were enrolled in prospective cohort that included monthly preconception visits with vaginal fluid specimen collection and pregnancy testing. Four hundred fifty-eight women attempting pregnancy for ≤3 menstrual cycles at enrollment were eligible for this fecundability analysis.Participants/materials, Setting, Methods: At monthly preconception visits, participants reported the first day of last menstrual period and sexual behavior, underwent pregnancy testing and provided vaginal specimens. Discrete time proportional probabilities models were used to estimate fecundability ratios (FRs) and 95% CI in menstrual cycles with and without BV (Nugent score ≥ 7) at the visit prior to each pregnancy test. We also assessed the association between persistent BV (BV at two consecutive visits) and fecundability.Main Results and the Role Of Chance: Participants contributed 1376 menstrual cycles; 18.5% (n = 255) resulted in pregnancy. After adjusting for age, frequency of condomless sex and study site, BV at the visit prior to pregnancy testing was associated with a 17% lower fecundability (adjusted FR (aFR) 0.83, 95% CI 0.6-1.1). Persistent BV was associated with a 43% reduction in fecundability compared to cycles characterized by optimal vaginal health (aFR 0.57, 95% CI 0.4-0.8).Limitations, Reasons For Caution: Detection of vaginal microbiota disruption using Gram stain and a point-of-care test for elevated sialidase identified a non-optimal vaginal environment, but these non-specific methods may miss important relationships that could be identified by characterizing individual vaginal bacteria and bacterial communities using molecular methods. In addition, results may be subject to residual confounding by condomless sex as this was reported for the prior month rather than for the fertile window during each cycle.Wider Implications Of the Findings: Given the high global prevalence of BV and infertility, an association between BV and reduced fecundability could have important implications for a large number of women who wish to conceive. Multi-omics approaches to studying the vaginal microbiota may provide key insights into this association and identify potential targets for intervention.Study Funding/competing Interest(s): This work was supported by a National Institutes of Health grant (NICHD R01 HD087346-R.S.M.). R.S.M. received additional support for mentoring (NICHD K24 HD88229). E.M.L. was supported by pre- and post-doctoral fellowships (NIAID T32 AI07140, NICHD F32 HD100202). Data collection and management were made possible using REDCap electronic data capture tools hosted at the University of Washington's Institute of Translational Health Science supported by grants from NCATS/NIH (UL1 TR002319). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. R.S.M. receives research funding, paid to the University of Washington, from Hologic Corporation, and has received honoraria for consulting from Lupin Pharmaceuticals. L.E.M. receives research funding, paid to the University of Washington, from Hologic Corporation, and has received honoraria for service on scientific advisory boards from Hologic and Nabriva Therapeutics.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Children are increasingly recognized as secondary victims of intimate partner violence. This paper uses a unique UK longitudinal child development survey to study the relationship between verbal and physical abuse experienced by mothers and children's development up to the age of seven. Estimating production functions for cognitive, social, and socio-emotional skills, we find that exposure during pre-school years has a quantitatively important negative effect on socio-emotional skills among toddlers and negatively affects cognitive and social skills after the age of three. The estimated impact on cognitive development is consistent with measures of cognitive skills based on school-based tests. [ABSTRACT FROM AUTHOR]

Background COVID-19 has disproportionately affected older people. Objective The objective of this paper to investigate whether frailty is associated with all-cause mortality in older hospital inpatients, with COVID-19. Design Cohort study. Setting Secondary care acute hospital. Participants Participants included are 677 consecutive inpatients aged 65 years and over. Methods Cox proportional hazards models were used to examine the association of frailty with mortality. Frailty was assessed at baseline, according to the Clinical Frailty Scale (CFS), where higher categories indicate worse frailty. Analyses were adjusted for age, sex, deprivation, ethnicity, previous admissions and acute illness severity. Results Six hundred and sixty-four patients were classified according to CFS. Two hundred and seventy-one died, during a mean follow-up of 34.3 days. Worse frailty at baseline was associated with increased mortality risk, even after full adjustment (P  = 0.004). Patients with CFS 4 and CFS 5 had non-significant increased mortality risks, compared to those with CFS 1–3. Patients with CFS 6 had a 2.13-fold (95% CI 1.34–3.38) and those with CFS 7–9 had a 1.79-fold (95% CI 1.12–2.88) increased mortality risk, compared to those with CFS 1–3 (P  = 0.001 and 0.016, respectively). Older age, male sex and acute illness severity were also associated with increased mortality risk. Conclusions Frailty is associated with all-cause mortality risk in older inpatients with COVID-19. [ABSTRACT FROM AUTHOR]

Taking advantage of the ability of modern missing data treatments in epidemiological research (e.g. multiple imputation) to recover power while avoiding bias in the presence of data that is missing completely at random, planned missing data designs allow researchers to deliberately incorporate missing data into a research design. A planned missing data design may be done by randomly assigning participants to have missing items in a questionnaire (multiform design) or missing occasions of measurement in a longitudinal study (wave-missing design), or by administering an expensive gold-standard measure to a random subset of participants while the whole sample is administered a cheaper measure (two-method design). Although not common in epidemiology, these designs have been recommended for decades by methodologists for their benefits-notably that data collection costs are minimized and participant burden is reduced, which can increase validity. This paper describes the multiform, wave-missing and two-method designs, including their benefits, their impact on bias and power, and other factors that must be taken into consideration when implementing them in an epidemiological study design. [ABSTRACT FROM AUTHOR]

Microvascular dysfunction (MVD) is a common pathophysiological change that occurs in various diseases, such as type 2 diabetes mellitus (T2DM), heart failure, dementia, and depression. Recent technical advances have enabled noninvasive measurement and quantification of microvascular changes in humans. In this paper, we describe the protocols of the microvascular measurements applied in the Maastricht Study, an ongoing prospective, population-based cohort study of persons aged 40–75 years being carried out in the southern part of the Netherlands (baseline data assessment, November 2010–January 2020). The study includes a variety of noninvasive measurements in skin, retina, brain, and sublingual tissue, as well as plasma and urine biomarker assessments. Following this, we summarize our main findings involving these microvascular measurements through the end of 2018. Finally, we provide a brief perspective on future microvascular investigations within the framework of the Maastricht Study. [ABSTRACT FROM AUTHOR]

Epidemiologists often compare the observed number of deaths in a cohort with the expected number of deaths, obtained by multiplying person-time accrued in the cohort by mortality rates for a reference population (ideally, a reference that represents the mortality rate in the cohort in the absence of exposure). However, if exposure is hazardous (or salutary), this calculation will not consistently estimate the number of deaths expected in the absence of exposure because exposure will have affected the distribution of person-time observed in the study cohort. While problems with interpretation of this standard calculation of expected counts were discussed more than 2 decades ago, these discussions had little impact on epidemiologic practice. The logic of counterfactuals may help clarify this topic as we revisit these issues. In this paper, we describe a simple way to consistently estimate the expected number of deaths in such settings, and we illustrate the approach using data from a cohort study of mortality among underground miners. [ABSTRACT FROM AUTHOR]

Social scientists increasingly link survey data with administrative records. However, data protection legislation often requires respondents’ informed consent prior to record linkage. This has confronted research with nontrivial refusal rates in combination with selectivity of the consent decision. In longitudinal surveys, linkage requests may also increase attrition rates in subsequent waves, as many respondents perceive record linkages negatively. Hence, in panel surveys, both nonresponse forms potentially bias the resulting datasets. The present paper examines (a) whether we can minimize consent refusals in a longitudinal survey by varying which survey wave includes the linkage request and (b) whether such requests increase subsequent attrition. To test this, we implement a randomized survey experiment within a face-to-face household panel survey focusing on migrants in Germany. Respondents of the IAB-SOEP Migration Sample, conducted by the Institute for Employment Research (IAB) and the Socio-Economic Panel study (SOEP), were randomly allocated into three groups: first, a control group without record linkage; a second group that was asked in wave 1 (2013) to allow data linkage to administrative employment and benefits records held by the Federal Employment Agency; and a third group that was asked the same question in wave 2 (2014). We found neither significant differences in consent rates when introducing the request in wave 1 or 2 nor significant differences in panel attrition in subsequent waves. Therefore, results suggest that requesting consent to link records in wave 1 of a panel study provides the largest quantity of linked data without inflating panel attrition. [ABSTRACT FROM AUTHOR]

Background The aim of this paper is to describe UK-trained doctors' early intentions about seeking careers in public health and their eventual speciality destinations. Methods Analysis of longitudinal studies of medical graduates from all UK medical schools in selected year-of-qualification cohorts from 1974 to 2008; data collected by postal questionnaires at various times after qualifying; and selection, for this paper, of doctors who expressed an early preference for a career in public health and/or who eventually practised in it. Results Of all doctors eventually practising in public health, for whom we had early choices, public health had been the unreserved first choice of 8% (10/125) in their first post-qualification year, 27% (33/122) in their third year and 59% (51/86) in their fifth year. Including first choices for public health ‘tied’ with an equal preference for a different speciality, and doctors' second and third choices for public health, 19% (24/125) of practising public health doctors had considered public health as a possible career in their first post-graduation year, 41% (50/122) in the third and 83% (71/86) in the fifth year. Conclusions Comparisons with other specialities show that doctors in public health chose their speciality relatively late after qualification. [ABSTRACT FROM PUBLISHER]

This paper has the following aims: (i) to explore the extent to which students who received an intervention involving HIV/AIDS and sexuality perceived that their teacher cared for their health and well-being, (ii) to investigate the characteristics of students who reported to have caring teachers and (iii) to document the association between students’ perceptions of care and reported onset of sexual activity. Data were obtained from the second follow-up survey of a prospective study carried out among high school students in South Africa (Cape Town and Mankweng). We analyzed data from 3483 students who met the inclusion criteria. Students from the intervention group perceived greater care from teachers than students in the control group. Female students and students from Cape Town perceived having received more care, and their perception of care was associated with the number of lessons received, how often students expressed their opinions in class and how often teachers talked about HIV/AIDS, condoms and abstinence. Students who perceived that their teacher cared for their health and well-being were less likely to initiate sexual intercourse. This is the first paper to demonstrate the salience of the concept of care in studies of school-based HIV/AIDS prevention programs in sub-Saharan Africa. [ABSTRACT FROM PUBLISHER]

BACKGROUND Several studies have examined the relationship between direct antisperm antibody (ASA) levels in semen and pregnancy rate after advanced assisted reproductive technologies (ARTs) but the results have been inconsistent. The aim of our study was to further evaluate the relationship between ASA and pregnancy after IVF or ICSI by systematic review and meta-analysis. METHODS We conducted a systematic Medline search of all relevant full papers on direct semen ASA and pregnancy after IVF or ICSI. Three investigators independently reviewed the papers, followed by group discussion to choose the included papers. Meta-analysis was performed to get an odds ratio (OR) for the effect of ASA on pregnancy using IVF or ICSI. RESULTS The study identified and analyzed 16 valid studies (10 IVF and 6 ICSI). The study characteristics (including the ASA cutoff values) were heterogeneous. Our meta-analysis revealed that the combined OR for failure to achieve a pregnancy using IVF or ICSI in the presence of positive semen ASA was 1.22 (95% CI: 0.84, 1.77) and 1.00 (95% CI: 0.72, 1.38), respectively. The overall (IVF + ICSI) combined OR was 1.08 (95% CI: 0.85, 1.38). CONCLUSION This systematic review and meta-analysis indicate that semen antisperm antibodies are not related to pregnancy rates after IVF or ICSI, suggesting that both forms of ART remain viable options for infertile couples with semen ASA. However, additional, well-designed prospective studies using appropriate ASA cutoff levels are needed to further address this issue. [ABSTRACT FROM AUTHOR]

This paper presents the largest cohort to date of infants under 1 year of age treated with mebendazole. We evaluated the occurrence of mebendazole-associated clinical and laboratory toxicity as safety data in this age group are currently lacking. [ABSTRACT FROM AUTHOR]

Background The emergence of new types of tobacco and tobacco-related products on the European Union (EU) market has precipitated the possibility for both poly-tobacco use and transitions between products. In the EU, the regulatory environment has shifted with the implementation of the European Tobacco Products Directive (TPD) in May 2016, which may influence consumer transitions between products. Methods The aim of this paper was to examine trends and transitions in tobacco products from 2016 to 2018 -before and after implementation of the TPD in the EU. Data come from Wave 1 (pre-TPD) and Wave 2 (post-TPD) of the EUREST-PLUS ITC Six European Country Survey, a cohort study of adults who at the time of recruitment were smokers from six EU countries- Germany, Greece, Hungary, Poland, Romania, and Spain. D (N = 3195). Bivariate and logistic regression analyses of weighted data was conducted using SAS-callable SUDAAN Results Overall, among those who smoked factory-made cigarettes (FM) only at Wave 1, 4.3% switched to roll-your-own tobacco (RYO) only. Among RYO only users at Wave 1, 17.0% switched to FM only, however compared to all other countries, respondents from Hungary had the highest percentage of FM only users at Wave 1 switch to RYO only at Wave 2 (18.0%). Conclusions The most prominent transition overall was from smoking RYO exclusively at Wave 1 to smoking FM tobacco exclusively at Wave 2, however this varied across countries. As the tobacco control regulatory environment of the EU develops, it is important to continue to monitor transitions between types of products, as well as trends in cessation. [ABSTRACT FROM AUTHOR]

Aims The objective of this paper was to examine 20-year trends of the socioeconomic status (SES) measures income and employment and their association with current alcohol use behaviors in Danish adults aged 60–70. Methods Data from The Danish National Health Survey 2013 and the baseline assessment of the Elderly Study (2013–2016) were combined to form four groups from the general population with various drinking patterns, but with no recent treatment for alcohol use disorder (AUD), and one group seeking treatment: Abstinent (n  = 691), low- (n  = 1978), moderate- (n  = 602), and high-risk (HR) drinkers (n  = 467), and DSM-5 AUD seeking treatment (n  = 262). For all groups, Danish national register data were linked at the individual level obtain find annual information on income and employment during the 20 years prior to interview. Mixed effects models were utilized to model trajectories of income and employment for the five groups. Results Lower income and employment status was observed from middle-aged adulthood when comparing 12-month abstinence or AUD to individuals with low or moderate alcohol consumption. At the end of the study period, moderate-risk drinkers experienced an increase, and HR drinkers a decrease, in income and rate of employment relative to the low-risk drinkers. Conclusions Alcohol use behaviors observed in older adults are related to distinct long-term trajectories regarding income and employment status, which are observable already in middle-aged adulthood. [ABSTRACT FROM AUTHOR]

The case-control study design has evolved substantially over the past half century. The design has long been recognized as a way to increase efficiency by studying fewer subjects than would be required for a full cohort study. Historically, it was thought that case-control studies required a rare disease assumption for valid risk ratio estimation, but it was later realized that rare disease was not necessary. Over time, the design and analysis methods were further modified to allow estimation of rate ratios or to allow each person to serve as his/her own control (as we see with case-cohort and case-crossover studies, for example). We now understand that efficiency can be increased through the use of outcome-dependent sampling not only for dichotomous outcomes but also for continuous outcomes in longitudinal studies with repeated outcome measurement during follow-up. In their accompanying paper, Schildcrout et al. (Am J Epidemiol. 2019;000(00):000–000) contribute to our understanding, clearly summarizing many recent advances in study design and analyses that allow more general and efficient use of case-control studies. Their simulations demonstrate that improved efficiency is achieved with these methods when the goal is to estimate associations of exposure with trajectories and patterns of change over time. Here we comment on application of some of these generalized case-control methods to causal inference. [ABSTRACT FROM AUTHOR]

Background: Miscarriage is the spontaneous loss of a pregnancy before 12 weeks (early miscarriage) or from 12 to 24 weeks (late miscarriage) of gestation. Miscarriage occurs in one in five pregnancies and can have considerable physiological and psychological implications for the patient. It is also associated with significant health care costs. There is evidence that potentially preventable infections may account for up to 15% of early miscarriages and up to 66% of late miscarriages. However, the provision of associated screening and management algorithms is inconsistent for newly pregnant women. Here, we review recent population-based studies on infections that have been shown to be associated with miscarriage.Methods: Our aim was to examine where the current scientific focus lies with regards to the role of infection in miscarriage. Papers dating from June 2009 with key words 'miscarriage' and 'infection' or 'infections' were identified in PubMed (292 and 327 papers, respectively, on 2 June 2014). Relevant human studies (meta-analyses, case-control studies, cohort studies or case series) were included. Single case reports were excluded. The studies were scored based on the Newcastle - Ottawa Quality Assessment Scale.Results: The association of systemic infections with malaria, brucellosis, cytomegalovirus and human immunodeficiency virus, dengue fever, influenza virus and of vaginal infection with bacterial vaginosis, with increased risk of miscarriage has been demonstrated. Q fever, adeno-associated virus, Bocavirus, Hepatitis C and Mycoplasma genitalium infections do not appear to affect pregnancy outcome. The effects of Chlamydia trachomatis, Toxoplasma gondii, human papillomavirus, herpes simplex virus, parvovirus B19, Hepatitis B and polyomavirus BK infections remain controversial, as some studies indicate increased miscarriage risk and others show no increased risk. The latest data on rubella and syphilis indicate increased antenatal screening worldwide and a decrease in the frequency of their reported associations with pregnancy failure. Though various pathogens have been associated with miscarriage, the mechanism(s) of infection-induced miscarriage are not yet fully elucidated.Conclusions: Further research is required to clarify whether certain infections do increase miscarriage risk and whether screening of newly pregnant women for treatable infections would improve reproductive outcomes. [ABSTRACT FROM AUTHOR]

Focus of Presentation Cohort study recruitment can be complex, often requiring extensive pre-screening to recruit sufficient numbers of exposed and unexposed participants. We discuss a prospective study of the impact of racism on adult health in New Zealand (NZ), with emphasis on propensity-score based sampling and recruitment methods accessing participants from a national survey (NZ Health Survey 2017/18, n = 12,530 eligible adults). Discussion will cover sampling design, response rate, and confounder balance in the final sample. Key empirical results will be summarised. Findings The NZHS provided a sampling frame with complete baseline exposure and covariate data, giving n = 2,099 exposed individuals (reported racial discrimination on NZHS). A propensity-score model (stratified by ethnicity) allowed invitation of unexposed individuals balanced on key sociodemographic confounders. Recruitment used postal invitations with telephone follow-up: individuals could respond by paper survey, online questionnaire or telephone interview. Response rate was 54%, with comparable rates in exposed/unexposed individuals, with key sociodemographic factors well-balanced by exposure status. Conclusions/Implications Racism is an important determinant of health inequity, with limited prospective research in New Zealand. Our approach enabled appropriate recruitment from a sampling frame with baseline exposure status (NZHS), including allowance for exposure variability by ethnicity. Propensity-score matching on baseline covariates allowed for balance on key confounders at invitation, with balance maintained in the final sample. Key messages Secondary sampling from large national surveys can provide efficient recruitment for prospective studies. We achieved a highly satisfactory response rate, and propensity-score based sampling substantially balanced confounders between exposed and unexposed groups, enhancing study validity. [ABSTRACT FROM AUTHOR]

Background Aimed to compare the prevalence, characteristics, and associated mortality risk of frailty in Northern Ireland (NI) and the Republic of Ireland (ROI). Methods Secondary analysis of the first wave of two nationally representative cohorts, the Northern Ireland Cohort for the Longitudinal Study of Ageing or NICOLA study (N  = 8504) and the Irish Longitudinal Study on Ageing or TILDA study (N  = 8504). Frailty was assessed using a harmonized accumulation deficits frailty index (FI) containing 30 items. FI scores classified individuals as non-frail (<0.10), pre-frail (0.10–0.24) and frail (≥0.25). Linkage to respective administrative data sources provided mortality information with a follow-up time of 8 years. Results The prevalence of frailty was considerably higher in NI compared with the ROI (29.0% compared with 15.0%), though pre-frailty was slightly lower (35.8% and 37.3%, respectively). Age, female sex, and lower socio-economic status were consistently associated with a higher likelihood of both pre-frailty and frailty. In the pooled analysis, both frailty and pre-frailty were higher in NI (RR = 2.68, 95% CIs 2.45, 2.94 and RR = 1.30, 95% CIs 1.21, 1.40, respectively). Frailty was associated with an increased mortality risk in both cohorts, even after full adjustment for all other characteristics, being marginally higher in TILDA than in NICOLA (HR = 2.43, 95% CIs 2.03, 2.91 vs. HR = 2.31, 95% CIs 1.90, 2.79). Conclusions Frailty is a major public health concern for both jurisdictions. Further research and monitoring are required to elucidate why there is a higher prevalence in NI and to identify factors in early life that may be driving these differences. [ABSTRACT FROM AUTHOR]

Background According to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, both immunohistochemical HER2 (3+) and HER2 (2+)/in situ hybridization (ISH) amplified [HER2 (2+)/ISH+] breast cancers (BCs) fall under the HER2-positive BC category. However, there is a lack of studies exploring the difference of neoadjuvant therapeutic response between patients with HER2 (3+) and HER2 (2+)/ISH+ early BC. We aimed to evaluate the neoadjuvant therapeutic response, long-term outcome, and intrinsic subtype heterogeneity between HER2 (3+) and HER2 (2+)/ISH+ BC. Methods We examined 2 distinct cohorts. Cohort 1 (C1) encompassed 2648 patients with HER2-positive early BC diagnoses, and they received neoadjuvant therapy (NT) and surgery between January 1, 2009 and December 31, 2022, from the Shanghai Jiao Tong University Breast Cancer Data Base. Cohort 2 (C2) comprised 135 patients with early-stage HER2-positive BC who underwent NT and surgery at Henan Cancer Hospital from January 1, 2021, to December 31, 2022. These patients had available genomic and transcriptomic data at their disposal. C1 and C2 were further categorized into 2 patient cohorts as follows: (1) patients with IHC HER2 (3+) early BC [HER2 (3+) group], (2) patients with HER2 (2+)/ISH+ early BC [HER2 (2+)/ISH+ group]. Among those excluded from the analysis were patients < 18 years or >80 years of age. Clinicopathological parameters, long-term outcomes, and intrinsic subtypes were analyzed. Results In the C1 population, 83.7% had HER2 (3+) BC, while 16.3% had HER2 (2+)/ISH+ BC. Patients with HER2 (3+) had a significantly higher pathological complete response (PCR) rate (38.9%) than patients with HER2 (2+)/ISH+ (18.1%; P  < .001), but the disease-free survival (DFS) was comparable after a median follow-up of 29 months (P  = .556). The addition of trastuzumab or trastuzumab plus pertuzumab to neoadjuvant chemotherapy (NAC) improved PCR rates and DFS in HER2 (3+) BC but not in HER2 (2+)/ISH+ BC. In the C2 population, 97.75% HER2 (3+) and 52.17% HER2 (2+)/ISH+ were HER2 enriched (HER2E) subtype (P  < .001). HER2E showed increased PCR rates compared to non-HER2E (P  = .004). Conclusions Compared to HER2 (3+) BC, the limited effectiveness of neoadjuvant trastuzumab and pertuzumab therapy for HER2 (2+)/ISH+ BC is due to subtype heterogeneity. Reassessment of targeted therapy efficacy in patients with HER2 (2+)/ISH+ BC is essential. [ABSTRACT FROM AUTHOR]

Background As a newly identified subtype of HER2-negative tumors associated with a less favorable prognosis, it remains crucial to evaluate potential prognostic and predictive factors, particularly non-invasive biomarkers, for individuals with human epidermal growth factor 2 (HER2) low early-stage breast cancer (EBC). Multiple investigations have highlighted that HER2-negative patients with EBC exhibiting high homologous recombination deficiency (HRD) scores display lower rates of pathological complete response (PCR) to neoadjuvant chemotherapy (NAC). Nevertheless, no study to date has explored the correlation between HRD and the long-term prognosis in HER2-low patients with EBC. Patients and methods This retrospective observational study focuses on primary EBC sourced from The Cancer Genome Atlas dataset (TCGA). It reveals the gene mutation landscape in EBC with low HER2 expression and elucidates the tumor immune landscape across different HRD states. Utilizing bioinformatics analysis and Cox proportional models, along with the Kaplan-Meier method, the study assesses the correlation between HRD status and disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Subgroup analyses were conducted to identify potential variations in the association between HRD and prognosis. Results In the patients with HER2-low breast cancer, patients with homologous recombination related genes (HRRGs) defects had an HRD score about twice that of those without related genes mutations, and were at higher risk of acquiring ARID1A , ATM , and BRCA2 mutations. We also found that most immune cell abundances were significantly higher in EBC tumors with high HRD than in EBC tumors with low HRD or HRD-medium, particularly plasma B-cell abundance, CD8 T-cell abundance, and M1 macrophages. In addition, these tumors with HRD-high also appear to have significantly higher tumor immune scores and lower interstitial scores. Then, we analyzed the relationship between different HRD status and prognosis. There was statistical significance (P  = .036 and P  = .046, respectively) in DSS and PFI between the HRD-low and HRD-high groups, and patients with HRD-high EBC showed relatively poor survival outcomes. A medium HRD score (hazard ratio, HR = 2.15, 95% CI: 1.04-4.41, P  = .038) was a significant risk factor for PFI. Hormone receptor positivity is an important factor in obtaining medium-high HRD score and poor prognosis. Conclusion Higher HRD scores were associated with poorer PFI outcomes, particularly in people with HR+/HER2-low. Varied HRD states exhibited distinctions in HRRGs and the tumor immune landscape. These insights have the potential to assist clinicians in promptly identifying high-risk groups and tailoring personalized treatments for patients with HER2-low EBC, aiming to enhance long-term outcomes. [ABSTRACT FROM AUTHOR]

Background Ribociclib is approved for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) advanced breast cancer (ABC) treatment, in combination with endocrine therapy. Hematological, hepatic, and cardiac adverse events (AEs) emerged from pivotal trials, but little is known about cutaneous adverse events (CAEs). Patients and Methods We report data from a retrospective cohort study of all patients with HR+/HER2− ABC treated with ribociclib at Humanitas Cancer Center between June 2017 and December 2022. We recorded clinical-pathological data, the incidence, and treatment of ribociclib-related CAEs. These were evaluated according to the NCI-CTCAE v5.0 classification. Progression-free survival (PFS) was estimated by Kaplan-Meier method and the log-rank test was used to analyze differences between groups. Results Thirteen of 91 patients (14.3%) experienced treatment-related CAEs (mean time to the occurrence: 3.9 months). The most frequent CAEs were eczematous dermatitis (53.8%) and maculo-papular reaction (15.4%). Itch was reported by all 13 patients. The grade was G3 in 8 cases, G2 in 4, and G1 in 1. An integrated approach based on ribociclib dose modulation and dermatological interventions (oral antihistamine, moisturized cream, topical, and/or systemic steroids) could prevent ribociclib discontinuation in most patients. At a median follow-up of 20 months, the median PFS was 13 months (range, 1-66) with a better PFS curves for patients experiencing CAEs (P  = .04). Conclusion We mapped frequency and types of ribociclib-induced CAEs. An interdisciplinary management of CAEs incorporated into routine care may reduce the rate of drug discontinuation thus potentially contributing to better long-term outcomes. [ABSTRACT FROM AUTHOR]

Background Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems. Methods Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of covariates that impacted OS and a validation set. Cox models were used to determine the association of various factors with OS and a scoring system was created. Results We identified 383 patients with HCC with imaging and survival outcomes, n  = 255 in the training set and 128 in the validation cohort. Factors associated with OS on multivariate analysis included: tumor margin appearance on CT or MRI (hazard ratio [HR] 1.37, 95% CI, 1.01-1.88) with infiltrative margins portending worse outcomes than encapsulated margins, massive tumor morphology (HR 1.64, 95% CI, 1.06-2.54); >2 lesions (HR 2.06, 95% CI, 1.46-2.88), Child-Turcotte-Pugh class C (HR 3.7, 95% CI, 2.23-6.16), and portal vein thrombus (HR 2.41, 95% CI, 1.71-3.39). A new scoring system was developed and more predictive of OS than other well-established systems. Conclusions Incorporation of standardized imaging characteristics to established clinical and lab predictors of outcome resulted in an improved predictive scoring system for patients with HCC. [ABSTRACT FROM AUTHOR]