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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]

Introduction: The PROMIS Smoking Initiative has developed six item banks for assessment related to cigarette smoking among adult smokers (Nicotine Dependence, Coping Expectancies, Emotional and Sensory Expectancies, Health Expectancies, Psychosocial Expectancies, and Social Motivations). This article evaluates the psychometric performance of the banks when administered via short form (SF), computer adaptive test (CAT), and by mode of administration (computer vs. paper-and-pencil).Methods: Data are from two sources: an internet sample (N = 491) of daily and nondaily smokers who completed both SFs and CATs via the web and a community sample (N = 369) that completed either paper-and-pencil or computer administration of the SFs at two time points. First a CAT version of the PROMIS Smoking Assessment Toolkit was evaluated by comparing item administration rates and scores to the SF administration. Next, we considered the effect of computer versus paper-and-pencil administration on scoring and test-retest reliability.Results: Across the domains approximately 5.4 to 10.3 items were administered on average for the CAT. SF and CAT item response theory-scores were correlated from 0.82 to 0.92 across the domains. Cronbach's alpha for the four- to eight-item SFs among daily smokers ranged from .80 to .91 and .82 to .91 for paper-and-pencil and computer administrations, respectively. Test-retest reliability of the SFs ranged from 0.79 to 0.89 across mode of administration.Conclusions: Results indicate that the SF and CAT and computer and paper-and-pencil administrations provide highly comparable scores for daily and nondaily smokers, but preference for SF or CAT administration may vary by smoking domain. [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]

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]

Research has consistently identified embarrassment as a barrier hindering communication about sex across a range of professions. This paper presents an in-depth exploration of embarrassment as an experience in discussion about everyday sexuality between social workers and service users. It is based on the interpretative phenomenological analysis of eleven semi-structured interviews with social workers, working across a range of services in Israel. The analysis revealed that the experiences of embarrassment related to four aspects of one's identity. The term social self relates to embarrassment due to the breach of social codes, especially taboos about sex. Embodied self incorporates the embarrassment of social workers in facing their own physical feelings arising from interactions with services users. The term gendered self describes the uncomfortable feelings generated by a challenges to one's own sense of gendered identity. Finally, sexual self relates to the sexual autobiography of the practitioners and service users. The findings of this paper highlight a new perspective on embarrassment as a potential site for challenging dominant discourse and practice about sex and gender. The paper also highlight the relational interdependency between their embodied gendered sexual self and their social work practice that can serve to transform both self and practice. [ABSTRACT FROM AUTHOR]

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]

The selection, preparation and consumption of food are everyday experiences; however, the social and symbolic meaning attached to such practices varies widely. This paper presents findings from a research project which aimed to explore how such food practices were experienced, produced and maintained within residential children's homes in Scotland. Data were generated over a year-long fieldwork period during which participant observation was undertaken alongside qualitative interviews and/or focus groups with sixteen children and forty-six adults. The paper emphasises the importance of food and food practices to the ways in which children and staff living and working in residential care manage, express and contain feelings and emotions. [ABSTRACT FROM PUBLISHER]

Objective The aims of the study were to identify prognostic factors associated with health care outcomes in patients with musculoskeletal (MSK) conditions in primary care and to determine whether characteristics associated with choice of care modify treatment effects of a direct-access physical therapist–led pathway in addition to general practitioner (GP)–led care compared to GP-led care alone. Methods A secondary analysis of a 2-parallel-arm, cluster randomized controlled trial involving general practices in the United Kingdom was conducted. Practices were randomized to continue offering GP-led care or to also offer a direct-access physical therapist–led pathway. Data from adults with MSK conditions who completed the 6-month follow-up questionnaire were analyzed. Outcomes included physical health, opioid prescription, and self-reported health care utilization over 6 months. Treatment effect modifiers were selected a priori from associations in observational studies. Multivariable regression models identified potential prognostic factors, and interaction analysis tested for potential treatment effect modifiers. Results Analysis of 767 participants indicated that baseline pain self-efficacy, pain severity, and having low back pain statistically predicted outcomes at 6 months. Higher pain self-efficacy scores at baseline were associated with improved physical health scores, reduced opioid prescription, and less health care utilization. Higher bodily pain at baseline and having low back pain were associated with worse physical health scores and increased opioid prescription. Main interaction analyses did not reveal that patients' age, level of education, duration of symptoms, or MSK presentation influenced response to treatment, but visual trends suggested those in the older age group proceeded to fewer opioid prescriptions and utilized less health care when offered direct access to physical therapy. Conclusions Patients with MSK conditions with lower levels of pain self-efficacy, higher pain severity, and presenting with low back pain have less favorable clinical and health care outcomes in primary care. Prespecified characteristics did not modify the treatment effect of the offer of a direct-access physical therapist–led pathway compared to GP-led care. Impact Patients with MSK conditions receiving primary care in the form of direct-access physical therapist–led or GP-led care who have lower levels of self-efficacy, higher pain severity, and low back pain are likely to have a less favorable prognosis. Age and duration of symptoms should be explored as potential patient characteristics that modify the treatment response to a direct-access physical therapist–led model of care. [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]

Comments on research studies concerning different approaches to the analysis of ordered longitudinal data. Strenghts and weaknesses of summary and multilevel approaches; Significance of the size of the variation among individuals surveyed in the research studies.

Study Question: Does pre-treatment with a low dose of mifepristone improve irregular vaginal bleeding patterns during the initial 3 months after LNG-IUS placement?Summary Answer: Mifepristone treatment prior to LNG-IUS insertion results in significantly lower bleeding and spotting rates but no significant reduction post insertion.What Is Known Already: One of the leading causes of premature discontinuation of the LNG-IUS is unscheduled bleeding in the first months following its insertion. Up to now, there has been no effective treatment to prevent this side effect which reduces continuation rates for one of the most effective contraceptives.Study Design, Size, Duration: This randomized, double blinded, controlled trial was conducted between 2009 and 2015. In total, 68 women opting for a LNG-IUS were screened for eligibility, of whom 58 were randomized at a ratio of 1:1 in blocks of 10 to pre-treatment with mifepristone or a comparator. The main outcome was the rate of bleeding and spotting days reported during the first 3 months post LNG-IUS 52 mg placement.Participants/materials, Setting, Methods: Healthy women with regular and normal menstrual cycles aged 18-43 years were enrolled at a single center in a university hospital; 29 were allocated to 2 months pre-treatment with a low dose mifepristone and 29 to the comparator prior to insertion of the LNG-IUS. Women were advised to use barrier methods during the pre-treatment period. Bleeding diaries were collected for the pre-treatment period and for the first 6 months after the LNG-IUS placement.Main Results and the Role Of Chance: There were no differences in demographics or baseline characteristics between the study groups. Data for analysis of the main outcome were contributed by a per protocol population of 19 women per group. There was a significant lower bleeding and spotting rate in the mifepristone group (-17.8% points, P < 0.001) after 2 months of pretreatment but after the LNG-IUS insertion no significant difference could be seen. While no pregnancies occurred prior to LNG-IUS insertion in the mifepristone group, there were three unintended pregnancies in the comparator group which emphasizes the need for a reliable contraceptive potential in any pre-treatment regiment used in clinical practice.Limitations, Reasons For Caution: The use of mifepristone prior to the LNG-IUS insertion in this trial was used as prophylaxis against unscheduled bleeding after the placement of the device. Although this side effect constitutes a major concern in a clinical setting, only a subset of women are at risk. This is the first study using pre-treatment to attempt improved bleeding control. The differences were small and the effect was short lasting but the reduced rate of bleeding and spotting observed during the first month following LNG-IUS insertion, even though not statistically significant, indicates that this approach may be further explored. The fact that there were three pregnancies in the comparator group stresses the need for any pre-treatment to also protect against unplanned pregnancy.Wider Implications Of the Findings: Modified treatment protocols of mifepristone could be used prior to the LNG-IUS insertion to investigate possible further improvement of the outcome. The effect size of the current dose used might have been more prominent in women with LNG-IUS if the treatment also continued some weeks after the placement of the device. Although the low dose of mifepristone used in this trial is not available in Europe, other progesterone receptor modulators currently available could be investigated in larger clinical trials. To avoid unintended pregnancy in the pretreatment period, the dosage used should, ideally, also be effective for contraception and the pretreatment period should be kept as short as possible.Study Funding/competing Interest(s): This study was funded by the Swedish Research Council (2012-2844, 2017-00932), Stockholm County Council and Karolinska Institutet (ALF). Conflicts of interests for K.G.D. and H.K.K. are listed at the end of the paper. The other authors have no conflicts of interest.Trial Registration Number: EudraCT number 2009-009014-40. Regional ethical review board at Karolinska Institutet permit 2009/144-31/4.Trial Registration Date: 20 July 2009.Date Of First Patient’s Enrolment: 24 November 2009. [ABSTRACT FROM AUTHOR]

Social Work Practices (SWPs) were established in England in 2009 to deliver social work services to looked after children and care leavers. The introduction of independent social work-led organisations generated controversy focused on issues such as the privatisation of children's services and social workers' conditions of employment. This paper reports early findings from the evaluation of four of these pilots, drawing on interviews with children and young people, staff, and local authority and national stakeholders. The SWPs assumed a variety of organisational forms. The procurement process was demanding, with protracted negotiations over matters such as budgetary control and providing a round-the-clock service. Start-up was facilitated by an established relationship between the SWP provider and the local authority. Once operational, SWPs continued to rely on local authorities for various functions; in most cases, local authorities retained control of placement budgets. Levels of consultation and choice offered to children and young people regarding the move to an SWP varied considerably. Children's understanding about SWPs was generally low except in the pilot where most children retained their original social worker. These early findings show some dilution of the original SWP model, while the pilots' diversity allows the benefits of particular models to emerge. [ABSTRACT FROM AUTHOR]

Background: Cancer-related cognitive dysfunction has mostly been attributed to chemotherapy; this explanation, however, fails to account for cognitive dysfunction observed in chemotherapy-naïve patients. In a controlled, longitudinal, multisite study, we tested the hypothesis that cognitive function in breast cancer patients is affected by cancer-related post-traumatic stress.Methods: Newly diagnosed breast cancer patients and healthy control subjects, age 65 or younger, underwent three assessments within one year, including paper-and-pencil and computerized neuropsychological tests, clinical diagnostics of post-traumatic stress disorder (PTSD), and self-reported cognitive function. Analysis of variance was used to compare three groups of participants-patients who did or did not receive chemotherapy and healthy control subjects-on age- and education-corrected cognitive performance and cognitive change. Differences that were statistically significant after correction for false discovery rate were investigated with linear mixed-effects models and mediation models. All statistical tests were two-sided.Results: Of 226 participants (166 patients and 60 control subjects), 206 completed all assessment sessions (attrition: 8.8%). Patients demonstrated overall cognitive decline (group*time effect on composite z -score: -0.13, P = .04) and scored consistently worse on Go/Nogo errors. The latter effect was mediated by PTSD symptoms (mediation effect: B = 0.15, 95% confidence interval = 0.02 to 0.38). Only chemotherapy patients showed declined reaction time on a computerized alertness test. Overall cognitive performance correlated with self-reported cognitive problems at one year ( T = -0.11, P = .02).Conclusions: Largely irrespective of chemotherapy, breast cancer patients may encounter very subtle cognitive dysfunction, part of which is mediated by cancer-related post-traumatic stress. Further factors other than treatment side effects remain to be investigated. [ABSTRACT FROM AUTHOR]

Background: The aim of this paper is to compare three models for exploring the links between different measures of adult socioeconomic position (SEP)-education, occupation, income-and psychosocial health. Model I is a basic univariate regression model with psychosocial health as the outcome and a measure of SEP as the predictor. Model II is a multiple regression model with psychosocial health as the outcome with all three measures of SEP allocated the same temporal position as predictors. Model III treats education, a distal measure of SEP, as antecedent to the proximal measures of SEP in the prediction equations linking SEP to health.Methods: Participants were drawn from the Whitehall II study, a prospective cohort study of British civil servants. Data analysed here are from Phase 5 (1997-1999) of data collection, 7830 individuals in all. The measures of SEP and psychosocial health were assessed via a self-administered questionnaire.Results: The three models can lead to completely different conclusions. Model III, our preferred model, shows education to have a stronger indirect effect on psychosocial health when compared to its direct effect. The indirect effect is due to the effect of education on proximal measures of social position, occupation, and income in this case.Conclusions: Results reported here support the hypothesis that a comparison of the relative importance of the different measures of social position in predicting health is meaningless if the causal relationships among these measures are not accounted for. [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs)-the gold standard for evaluating the effects of medical interventions-are notoriously challenging in terms of logistics, planning and costs. The cohort multiple randomized controlled trial approach is designed to facilitate randomized trials for pragmatic evaluation of (new) interventions and is a promising variation from conventional pragmatic RCTs. In this paper, we evaluate methodological challenges of conducting an RCT within a cohort. We argue that equally valid results can be obtained from trials conducted within cohorts as from pragmatic RCTs. However, whether this design is more efficient compared with conducting a pragmatic RCT depends on the amount and nature of non-compliance in the intervention arm. [ABSTRACT FROM AUTHOR]

This paper presents the results of an exploratory study linking the national data-sets for all children in need and child protection services in England. The study was informed by an emerging literature on systems thinking in public services, and aimed to examine variations and patterns of response in local authorities to demand for child welfare services in their area. One hundred and fifty-two local authority census returns and other statistical indicators covering up to a thirteen-year period were combined into a single data-set. Statistical analysis was undertaken to explore the characteristics of demand, workload and workforce, trends over time and variations between local authorities. The results showed that the overall system has become increasingly geared towards protective interventions, especially since the Baby P scandal of 2008. Deprivation levels continue to be the key driver of referrals and other categories of demand, and are strongly associated with variations in service response, particularly in the initial stages of referral and assessment. Implications are considered for the current organisation of child welfare services in light of recent reviews and reforms. [ABSTRACT FROM AUTHOR]

In the disaster literature, psycho-social recovery is conceptualised typically as the alleviation of traumatic stress, with the alleviation of disaster-related grief as a less prominent part of this. Yet, incorporating grief understandings into recovery conceptualisations post disaster is important. This paper explores these conceptualisations by analysing participants' bereavement experiences following the Black Saturday bushfires. It draws on data from Beyond Bushfires, a mixed-methods study (n = 1,016) in which survey and interview data relating to individual loss and recovery experiences were examined. The loss through death of friends and community members was found to be predictive of poorer mental health outcomes, although prolonged grief outcomes were rare. The sense of relationships as being 'like family' was identified by interviewees as an important dimension of their particular communities, as was coping with multiple deaths and the hierarchy of grief that emerged, and the stress of notifying others of these deaths. The implications of these impacts are considered for social work research and practice. [ABSTRACT FROM AUTHOR]

Objective: To study whether disposable diapers decrease the incidence of neonatal infections compared with cloth diapers in a level II neonatal intensive care unit (NICU). Method and Material: All neonates admitted to the NICU and having duration of stay >48 h were enrolled. Those babies with signs and symptoms of infection were screened with septic screen and/or blood culture. Results: The primary outcome of the study was incidence of probable sepsis. Of 253 babies enrolled in the study period, probable sepsis was present in 101 (39.9%) infants in the total study group and was higher in cloth diaper group as compared with disposable diaper group (p = 0.01). For an average NICU stay of 6 days, cloth diapers would cost Rs. 241 vs. Rs. 162 for disposable diaper for any infant. Conclusion: Usage of disposable diapers decrease the incidence of probable sepsis in babies admitted to NICU. It is also cost effective to use disposable diapers in the NICU. [ABSTRACT FROM AUTHOR]

There has until recently been relatively little research on child neglect in the UK, in spite of its prevalence and impact on children. This paper considers factors that relate to outcomes for neglected children based on a five-year follow-up study. The research used case file reviews to follow up a cohort of 138 neglected children in England who had been looked after and reunified. Half of the returns had broken down after two years, rising to almost two-thirds after five years. Rates of repeat neglect and abuse were also high. The study considered children's outcomes in terms of stability and well-being. Children over the age of six were at increased risk of experiencing placement instability after their returns ended and older children's cases were less well managed. Rates of stability varied widely by local authority. Poorer well-being was associated with persistent neglect and with the presence of behaviour problems prior to the child returning home, although children with such problems attained better well-being when case management prioritised safeguarding and planning. Earlier intervention, more protective and proactive action and better planning for children's futures, particularly for older children, are needed if their outcomes are to be improved. [ABSTRACT FROM AUTHOR]

Background: In a recent paper by Homer et al. (Resolving individuals contributing trace amounts of DNA to highly complex mixtures using high-density SNP genotyping microarrays. PLoS Genet 2008;4:e1000167), a method for detecting whether a given individual is a contributor to a particular genomic mixture was proposed. This prompted grave concern about the public dissemination of aggregate statistics from genome-wide association studies. It is of clear scientific importance that such data be shared widely, but the confidentiality of study participants must not be compromised. The issue of what summary genomic data can safely be posted on the web is only addressed satisfactorily when the theoretical underpinnings of the proposed method are clarified and its performance evaluated in terms of dependence on underlying assumptions.Methods: The original method raised a number of concerns and several alternatives have since been proposed, including a simple linear regression approach. In our proposed generalized estimating equation approach, we maintain the simplicity of the linear regression model but obtain inferences that are more robust to approximation of the variance/covariance structure and can accommodate linkage disequilibrium.Results: We affirm that, in principle, it is possible to determine that a 'candidate' individual has participated in a study, given a subset of aggregate statistics from that study. However, the methods depend critically on a number of key factors including: the ancestry of participants in the study; the absolute and relative numbers of cases and controls; and the number of single nucleotide polymorphisms.Conclusions: Simple guidelines for publication that are based on a single criterion are therefore unlikely to suffice. In particular, 'directed' summary statistics should not be posted openly on the web but could be protected by an internet-based access check as proposed by the P3G_Consortium et al. (Public access to genome-wide data: five views on balancing research with privacy and protection. PLoS Genet 2009;5:e1000665). [ABSTRACT FROM AUTHOR]

Background: Understanding the relationship between different aspects of disadvantage over time and domains of child development will facilitate the formulation of more precise policy responses. We examined the association between exposure to aspects of disadvantage over the childhood period (from 0-9 years) and child development at 10-11 years.Methods: We used data from the nationally representative birth cohort of the Longitudinal Study of Australian Children (n = 4979). Generalized linear models with log-Poisson link were used to estimate the association between previously derived disadvantage trajectories (in each of four lenses of sociodemographic, geographic environments, health conditions and risk factors, and a composite of these) and risk of poor child developmental outcomes. Population-attributable fractions were calculated to quantify the potential benefit of providing all children with optimal conditions for each developmental outcome.Results: Trajectories of disadvantage were associated with developmental outcomes: children in the most disadvantaged composite trajectory had seven times higher risk of poor outcomes on two or more developmental domains, compared with those most advantaged. Trajectories of disadvantage in different lenses were varyingly associated with the child development domains of socio-emotional adjustment, physical functioning and learning competencies. Exposure to the most advantaged trajectory across all lenses could reduce poor developmental outcomes by as much as 70%.Conclusions: Exposure to disadvantage over time is associated with adverse child development outcomes. Developmental outcomes varied with the aspects of disadvantage experienced, highlighting potential targets for more precise policy responses. The findings provide evidence to stimulate advocacy and action to reduce child inequities. [ABSTRACT FROM AUTHOR]

Longitudinal studies play an important role in evaluating the temporal behavior of occupational exposures. The purpose of this paper is to examine certain features of longitudinal data and to present a general conceptual framework by which these features may be taken into account so that statistically valid inferences can be made. Statistical methods that rely on the application of mixed-effects models are proposed for evaluating long-term trends in exposures to workplace contaminants. The mixed-effects model presented herein has fixed effects for trend components and random effects for workers, job groups, buildings and plants. These models differ from conventional techniques in that they accommodate hierarchically structured data and account for the correlation that may arise due to the clustering of measurements based on when and where the data were collected. While primary interest is focused on determining the magnitude of trends in exposure levels over time, the model also provides information about the magnitude of the sources of variation associated with different groupings of workers. Application of the mixed-effects model is illustrated with a large database of shift-long personal exposure measurements collected on workers exposed to nickel aerosols in the nickel-producing industry. [ABSTRACT FROM PUBLISHER]

Background Incontinence is common in hospitalised older adults but few studies report new incidence during or following hospitalisation. Objective To describe prevalence and incidence of incontinence in older inpatients and associations with clinical outcomes. Design Secondary analysis of prospectively collected data from consecutive consenting inpatients age 65 years and older on medical and surgical wards in four Australian public hospitals. Methods Participants self-reported urinary and faecal incontinence 2 weeks prior to admission, at hospital discharge and 30 days after discharge as part of comprehensive assessment by a trained research assistant. Outcomes were length of stay, facility discharge, 30-day readmission and 6-month mortality. Results Analysis included 970 participants (mean age 76.7 years, 48.9% female). Urinary and/or faecal incontinence was self-reported in 310/970 (32.0%, [95% confidence interval (CI) 29.0–35.0]) participants 2 weeks before admission, 201/834 (24.1% [95% CI 21.2–27.2]) at discharge and 193/776 (24.9% [95% CI 21.9–28.1]) 30 days after discharge. Continence patterns were dynamic within the peri-hospital period. Of participants without pre-hospital incontinence, 74/567 (13.1% [95% CI 10.4–16.1) reported incontinence at discharge and 85/537 (15.8% [95% CI 12.8–19.2]) reported incontinence at 30 days follow-up. Median hospital stay was longer in participants with pre-hospital incontinence (7 vs. 6 days, P  = 0.02) even in adjusted analyses and pre-hospital incontinence was significantly associated with mortality in unadjusted but not adjusted analyses. Conclusion Pre-hospital, hospital-acquired and new post-hospital incontinence are common in older inpatients. Better understanding of incontinence patterns may help target interventions to reduce this complication. [ABSTRACT FROM AUTHOR]

Multi-site research studies redefine cohort studies by simultaneously providing a cross-sectional snapshot of patients and monitoring them over time, to evaluate outcomes. However, careful design is crucial to minimize potential biases, such as seasonal variations, that may arise during the study period. Addressing snapshot study challenges requires strategic solutions: implementing multi-stage sampling for representativeness, providing rigorous data collection training, using translation techniques and content validation for cultural and linguistic appropriateness, streamlining ethical approval processes, and applying comprehensive data management for follow-up and missing data. These strategies can optimize the efficacy and ethicality of snapshot studies. [ABSTRACT FROM AUTHOR]

Objectives Negative age stereotypes have negative, assimilative effects on the subjective aging experience due to internalization processes, but sometimes positive contrast effects are reported as well, reflecting dissociation and downward comparisons. Our aim was thus to compare short-term and long-term consequences of age stereotypes on the subjective aging experience, to test the hypothesis that contrast effects are visible cross-sectionally, whereas internalization processes are observed when considering long-term changes. Methods We assessed age stereotypes and subjective age in a core sample of N = 459 participants (initial age range 30–80 years) from the Ageing as Future project across 3 consecutive measurement occasions spanning a longitudinal interval of 10 years. Short-term and long-term effects were estimated with latent growth models by assessing the effects of age stereotypes on the intercepts (cross-sectional) and on the slopes (longitudinal) of subjective age, respectively, while controlling for current self-views. Results Age stereotypes had opposite effects on subjective age depending on the time frame. A cross-sectional contrast effect was found, whereas longitudinal effects were assimilative in nature. Discussion Our findings support the time-dependent nature of the effects of age stereotypes on the subjective aging experience. Negative age stereotypes temporarily lead to a significantly younger subjective age, indicating dissociation from one's age group and downward comparison. In the long run, however, negative (positive) age stereotypes become internalized into the self-views of older people and are linked to a relatively older (younger) subjective age. [ABSTRACT FROM AUTHOR]

Aims Electronic health (eHealth) sources have great potential to improve patients' access to health information for self-management of secondary prevention after percutaneous coronary intervention (PCI). It remains unclear, however, whether patients are health-related digitally active and whether they have sufficient eHealth literacy. This study aimed to determine the extent to which patients after PCI are health-related digitally active at baseline, 2 and 6 months after PCI, and to determine the association between patients' eHealth literacy and their health-related digital activity. Methods and results This multicentre cohort study included patients at three large referral PCI centres in Norway (n = 1970). Data were collected from medical records, national registries, and patients' self-reports. The eHealth Literacy Scale (eHEALS) assessed patients' eHealth literacy. At baseline, 67% had used the internet to find health information. The mean eHEALS score was 25.71 (standard deviation 6.22), illustrating a lower level of eHealth literacy. There were substantial associations between eHealth literacy and use of the internet to find health information [coefficient 10.90, 95% confidence interval (CI) 8.05–14.57]. At the 2-month follow-up, there were substantial associations between baseline eHealth literacy and use of the internet to find information about health, prevention, illness, or treatment [odds ratio (OR) 1.19, 95% CI 1.14–1.24] and use of health applications (OR 1.15, 95% CI 1.08–1.22). Conclusion This study provides evidence that patients' level of eHealth literacy after PCI is associated to how patients use, and can make use of, eHealth technology for health information. Registration ClinicalTrials.gov (NCT03810612). [ABSTRACT FROM AUTHOR]

Background: The dramatic increase in mortality in Russia and Ukraine in the late 1980s and 1990s has been due to increases in certain causes of death, particularly cardiovascular disease and accidents and violence. In contrast, there has been a slight fall in mortality from cancer.Methods: This paper presents an analysis of trends and patterns in cancer mortality and examines four possible explanations for its recent fall: changes in data collection; cohort effects; competing mortality from other causes of death; and improvements in health care.Results: All contribute to some extent to the observed changes, with each affecting predominantly different age groups. There is evidence of a significant underrecording of cancer deaths among the elderly especially in rural areas and of significant changes in coding practices in the early 1990s. Competing mortality from cardiovascular diseases and accidents can explain some reduction in male deaths from cancer in middle age. Birth cohort effects can explain some reduction among males after early middle age and among females at all ages. The impact of changes in health care are more difficult to identify with certainty but there is evidence of reduced deaths from childhood leukaemia.Implications: Recent changes in mortality in Russia are complex and their understanding will require a multidisciplinary approach embracing demography, epidemiology and health services research. [ABSTRACT FROM AUTHOR]

Objectives To investigate associations between leisure-time physical activity (LPA) and injurious falls in older women and explore modification of associations by physical function and frailty. Methods Women born during 1946–51 from the Australian Longitudinal Study on Women's Health, injurious falls (self-reported fall with injury and/or medical attention) and self-reported weekly LPA (duration and type). We undertook cross-sectional and prospective analyses using data from 2016 [ n  = 8,171, mean (SD) age 68 (1)] and 2019 surveys (n  = 7,057). Associations were quantified using directed acyclic graph-informed logistic regression and effect modification examined using product terms. Results Participation in LPA as recommended by World Health Organization (150–300 min/week) was associated with lower odds of injurious falls in cross-sectional (adjusted Odds Ratio (OR) 0.74, 95% CI 0.61–0.90) and prospective analyses (OR 0.75, 95% CI 0.60–0.94). Compared with those who reported no LPA, cross-sectionally, odds of injurious falls were lower in those who reported brisk walking (OR 0.77, 95% CI 0.67–0.89) and vigorous LPA (OR 0.86, 95% CI 0.75–1.00). No significant association was found between different types of LPA and injurious falls prospectively. Only cross-sectionally, physical function limitation and frailty modified the association between LPA and injurious falls, with tendencies for more injurious falls with more activity in those with physical limitation or frailty, and fewer injurious falls with more activity among those without physical function limitation or frailty. Conclusion Participation in recommended levels of LPA was associated with lower odds of injurious falls. Caution is required when promoting general physical activity among people with physical limitation or frailty. [ABSTRACT FROM AUTHOR]

Objectives To demonstrate that unsuccessful treatment optimization in early disease is associated with difficult-to-treat RA (D2T-RA). Methods In this retrospective multicentre cohort study conducted from 09/2021–03/2022, we enrolled individuals fulfilling the 2010 ACR/EULAR RA criteria diagnosed 2000–2019. The outcome was D2T-RA by the EULAR definition. We used robust regression to examine the associations with delay, dose, duration of methotrexate and discontinuation of glucocorticoids. We tested through multinomial regression which factors were associated with persistent inflammatory refractory RA (PIRRA) or non-inflammatory refractory RA (NIRRA). Sensitivity analysis included a case-control study matching the year of diagnosis. Results We enrolled 48 D2T-RA patients and 145 non-D2T-RA controls. Methotrexate was started within 3 months in 16.7% of D2T-RA vs 33.1% of non-D2T-RA (P  = 0.011). Adequate duration of methotrexate was obtained in significantly fewer D2T-RA patients (70.8% vs 85.5%). Glucocorticoids were continued beyond 6 months in a higher proportion of D2T-RA patients (70.8% vs 33.8%, P  < 0.001). In multiple regression, treatment delay beyond 3 months (OR 0.3; 95% CI 0.1, 0.9) and non-discontinuation of glucocorticoids after 6 months (OR 4.6; 95% CI 2.2, 9.5) were significantly associated with D2T-RA. Treatment delay was significantly associated with PIRRA only, while non-discontinuation of glucocorticoids was significantly associated with PIRRA and NIRRA. Results were replicated in sensitivity analyses. Conclusion Failure to start methotrexate within 3 months and not being off glucocorticoids within 6 months are early predictive features of D2T-RA. [ABSTRACT FROM AUTHOR]

Aims Supervised exercise is a guideline-recommended treatment in intermittent claudication (IC). Hospital-based supervised exercise programmes (SEPs) are underutilized, while home-based structured exercise programmes (HSEPs) have attracted interest. The results from HSEP in IC are inconsistent and may confer no benefit over walk advice (WA) and be less effective than SEP. The aim of the study was to compare the effectiveness of best medical treatment, including Nordic pole WA alone, or WA + SEP or WA + HSEP for patients with IC. Methods and results This three-armed, multicentre randomized clinical trial enrolled patients with IC; all patients received best medical treatment including walking poles and the advice of regular Nordic pole walking (WA). For HSEP and SEP, additional exercise programmes were provided. The primarily investigated hypothesis was a non-inferiority analysis of SEP vs. HSEP regarding the 6-min walk test (6MWT) maximum distance, with a pre-defined non-inferiority margin of 50 m. Supporting outcomes included muscle endurance tests and the walking impairment questionnaire. Outcomes were assessed at baseline, 3, 6, and 12 months by a blinded evaluator. Altogether 166 patients (mean age 72 years; 59% males) were randomized. In HSEP and SEP, 24 and 26% patients, respectively, were fully exercise adherent. All three groups improved pain-free walking distance over time, but there were no significant intergroup differences. The intergroup 6MWT difference between SEP and HSEP from 0 to 12 months was –11.6 m, 95% confidence interval: –36.4 to 13.0 m (i.e. within the pre-specified non-inferiority margin). Conclusion The HSEP was non-inferior to SEP in patients with IC. There were no significant differences observed between the three groups at 1 year. Registration ClinicialTrials.gov: NCT02341716. [ABSTRACT FROM AUTHOR]

Objectives Previous research has suggested cross-national differences in the association between living alone and well-being among older adults. This study examined whether the association varied across social contexts within the country, Japan, in terms of varying degree of urbanization and differential time periods. Methods Data were obtained from a nine-wave nationwide longitudinal survey with a probability sample of Japanese adults aged 60 years and over. Respondents belonged to one of the three periods (around 1990, 2000, and 2015) according to the year they commenced participation. As many as 4,655 individuals from 575 municipalities provided 9,016 observation sets of two consecutive waves (t − 1 and t). Within a framework of the Hierarchical Generalized Linear Model, depressive symptoms at t were predicted based on changes in living arrangements from t − 1 to t and their cross-level interactions with gender, level of urbanization, and time period, controlling for various covariates at t −  1. Results In general, older adults living alone continuously as well as those who started living alone between the waves showed more depressive symptoms than those coresiding with someone continuously. However, this tendency was more prominent among rural residents than their urban counterparts, especially for men. Moreover, the effect of continuously living alone on depressive symptoms became smaller in Period 2015 than that in Period 1990, because of the increase in depressiveness in coresident older adults. Discussion Our findings indicate that living alone has a differential effect on older adults' well-being depending on the social context where residents' preferences for living arrangements and availability of formal services could vary. [ABSTRACT FROM AUTHOR]

Introduction Adverse drug reactions (ADRs) to anti-infectives affect especially hospitalized children and contribute to increased morbidity, mortality, length of stay, and costs in healthcare systems. Objective To assess ADRs associated with anti-infective use in Brazilian hospitalized children. Methods A prospective cohort study was conducted in 5 public hospitals over 6 months. Children aged 0–11 years and 11 months who were hospitalized for more than 48 h and prescribed anti-infectives for over 24 h were included. Results A total of 1020 patients met the inclusion criteria. Of these, 152 patients experienced 183 suspected ADRs. Most reactions were related to the gastrointestinal system (65.6%), followed by skin reactions (18.6%). Most reactions were classified as probable causality (58.5%), moderate severity (61.1%), and unavoidable (56.2%). Our findings showed that ADRs were associated with increased length of stay (P <.001), increased length of therapy (P <.015), increased days of therapy (P =.038), and increased number of anti-infectives prescribed per patient (P <.001). Conclusion Almost 15% of hospitalized children exposed to anti-infectives presented suspected ADRs. Their occurrence was classified as probable, of moderate severity, and unavoidable. ADRs were significantly influenced by the length of hospital stay and the number of anti-infectives prescribed per patient. [ABSTRACT FROM AUTHOR]

Objective To determine whether BILAG-2004 index is associated with the development of damage in a cohort of SLE patients. Mortality and development of damage were examined. Methods This was a multicentre longitudinal study. Patients were recruited within 12 months of achieving fourth ACR classification criterion for SLE. Data were collected on disease activity, damage, SLE-specific drug exposure, cardiovascular risk factors, antiphospholipid syndrome status and death at every visit. This study ran from 1 January 2005 to 31 December 2017. Descriptive statistics were used to analyse mortality and development of new damage. Poisson regression was used to examine potential explanatory variables for development of new damage. Results A total of 273 SLE patients were recruited with total follow-up of 1767 patient-years (median 73.4 months). There were 6348 assessments with disease activity scores available for analysis. During follow-up, 13 deaths and 114 new damage items (in 83 patients) occurred. The incidence rate for development of damage was higher in the first 3 years before stabilizing at a lower rate. Overall rate for damage accrual was 61.1 per 1000 person-years (95% CI: 50.6, 73.8). Analysis showed that active disease scores according to BILAG-2004 index (systems scores of A or B, counts of systems with A and BILAG-2004 numerical score) were associated with development of new damage. Low disease activity (LDA) states [BILAG-2004 LDA and BILAG Systems Tally (BST) persistent LDA] were inversely associated with development of damage. Conclusions BILAG-2004 index is associated with new damage. BILAG-2004 LDA and BST persistent LDA can be considered as treatment targets. [ABSTRACT FROM AUTHOR]

Background Although several coronavirus disease 2019 (COVID-19) vaccines initially showed high efficacy, there have been concerns because of waning immunity and the emergence of variants with immune escape capacity. Methods A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic severe acute respiratory syndrome coronavirus 2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period compared with unvaccinated individuals. Results The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received messenger RNA (mRNA)-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% confidence interval [CI], 82–93) 14 days to 3 months after dose 2 and 87% (95% CI, 38–97) 3 to 6 months after dose 2. During the Omicron-dominant period, VE was 56% (95% CI, 37–70) 14 days to 3 months since dose 2, 52% (95% CI, 40–62) 3 to 6 months after dose 2, 49% (95% CI, 34–61) 6+ months after dose 2, and 74% (95% CI, 62–83) 14+ days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (ie, mask wearing/high-risk behaviors) yielded similar estimates, respectively. Conclusions In Japan, where most are infection-naïve, and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level. [ABSTRACT FROM AUTHOR]

Background Successful tuberculosis (TB) treatment is necessary for disease control. The World Health Organization (WHO) has a target TB treatment success rate of ≥90%. We assessed whether the different types of unfavorable TB treatment outcome had different predictors. Methods Using data from Regional Prospective Observational Research for Tuberculosis-Brazil, we evaluated biological and behavioral factors associated with each component of unsuccessful TB outcomes, recently updated by WHO (death, loss to follow-up [LTFU], and treatment failure). We included culture-confirmed, drug-susceptible, pulmonary TB participants receiving standard treatment in 2015–2019. Multinomial logistic regression models with inverse probability weighting were used to evaluate the distinct determinants of each unsuccessful outcome. Results Of 915 participants included, 727 (79%) were successfully treated, 118 (13%) were LTFU, 44 (5%) had treatment failure, and 26 (3%) died. LTFU was associated with current drug-use (adjusted odds ratio [aOR] = 5.3; 95% confidence interval [CI], 3.0–9.4), current tobacco use (aOR = 2.9; 95% CI, 1.7–4.9), and being a person with HIV (PWH) (aOR = 2.0; 95% CI, 1.1–3.5). Treatment failure was associated with PWH (aOR = 2.7; 95% CI, 1.2–6.2) and having diabetes (aOR = 2.2; 95% CI, 1.1–4.4). Death was associated with anemia (aOR = 5.3; 95% CI, 1.4–19.7), diabetes (aOR = 3.1; 95% CI, 1.4–6.7), and PWH (aOR = 3.9; 95% CI, 1.3–11.4). Direct observed therapy was protective for treatment failure (aOR = 0.5; 95% CI,.3–.9) and death (aOR = 0.5; 95% CI,.2–1.0). Conclusions The treatment success rate was below the WHO target. Behavioral factors were most associated with LTFU, whereas clinical comorbidities were correlated with treatment failure and death. Because determinants of unsuccessful outcomes are distinct, different intervention strategies may be needed to improve TB outcomes. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, yet a significant proportion of individuals on clozapine continue to experience disabling symptoms, despite being treated with an adequate dose. There is a need for adjunct treatments to augment clozapine, notably for negative and cognitive symptoms. One such potential agent is the glutathione precursor N -acetylcysteine (NAC). Study Design A randomized double-blind, multi-center, placebo-controlled trial for clozapine patients with enduring psychotic symptoms (n = 84) was undertaken to investigate the efficacy of adjunctive NAC (2 g daily) for negative symptoms, cognition and quality of life (QoL). Efficacy was assessed at 8, 24, and 52 weeks. Study Results NAC did not significantly improve negative symptoms (P =.62), overall cognition (P =.71) or quality of life (Manchester quality of life: P =.11; Assessment of quality of life: P =.57) at any time point over a 1-year period of treatment. There were no differences in reported side effects between the groups (P =.26). Conclusions NAC did not significantly improve schizophrenia symptoms, cognition, or quality of life in treatment-resistant patients taking clozapine. This trial was registered with "Australian and New Zealand Clinical Trials" on the 30 May, 2016 (Registration Number: ACTRN12615001273572). [ABSTRACT FROM AUTHOR]

Background: Children in low- and middle-income countries are particularly vulnerable in the months following an initial health event (IHE), with increased risk of mortality caused mostly by infectious diseases. Due to exposure to a wide range of environmental stressors, hospitalization in itself might increase child vulnerability at discharge. The goal of this study was to disentangle the role of hospitalization on the risk of subsequent infection.Methods: Data from a prospective, longitudinal, international, multicenter mother-and-child cohort were analysed. The main outcome assessed was the risk of subsequent infection within 3 months of initial care at hospital or primary healthcare facilities. First, risk factors for being hospitalized for the IHE (Step 1) and for having a subsequent infection (Step 2) were identified. Then, inpatients were matched with outpatients using propensity scores, considering the risk factors identified in Step 1. Finally, adjusted on the risk factors identified in Step 2, Cox regression models were performed on the matched data set to estimate the effect of hospitalization at the IHE on the risk of subsequent infection.Results: Among the 1312 children presenting an IHE, 210 (16%) had a subsequent infection, mainly lower-respiratory infections. Although hospitalization did not increase the risk of subsequent diarrhoea or unspecified sepsis, inpatients were 1.7 (95% Confidence Intervals [1.0-2.8]) times more likely to develop a subsequent lower-respiratory infection than comparable outpatients.Conclusion: For the first time, our findings suggest that hospitalization might increase the risk of subsequent lower-respiratory infection adjusted on severity and symptoms at IHE. This highlights the need for robust longitudinal follow-up of at-risk children and the importance of investigating underlying mechanisms driving vulnerability to infection. [ABSTRACT FROM AUTHOR]

Objectives To better understand the temporal dynamics of progression from cognitive decline to onset of dementia in the dementia-free older population in the United States. Methods We used longitudinal data from a diverse national population-based sample of older adults (N = 531) in the Aging, Demographics, and Memory Study from the Health and Retirement Study with repeated measures of cognitive function and dementia diagnosis during 12 years of follow-up from 1996 to 2009. We employed joint latent class mixed models to estimate the association between cognitive change and competing risks of dementia and nondementia death and identify heterogeneity in the age profiles of such association adjusting for baseline characteristics. Results Our analyses found 3 latent classes with distinct age profiles of cognitive decline and associated risk of dementia and mortality: "Rapid Cognitive Decline" (19.6%), "Moderate Progression" (44.6%), and "Optimal Cognitive Aging" (35.8%). When simultaneously accounting for cognitive trajectories and time-to-dementia/death, we also found associations of baseline covariates with slope of cognitive decline (e.g. steeper decline among non-Hispanic Blacks and more educated) and risk of dementia (e.g. greater risk for females and apolipoprotein E-4 carriers, but no difference by education level) that differ substantially from those in separate longitudinal mixed models or survival models. Discussion The differential age patterns of cognitive decline predicting dementia incidences identified in this study suggest variation in the course of cognitive aging in older adults that may inform future etiological and intervention studies. [ABSTRACT FROM AUTHOR]

Aims: Interventional cardiology procedures may expose patients and staff to considerable radiation doses. We aimed to assess whether exposure to ionizing radiation during catheter ablation of supraventricular tachycardia (SVT) can be completely avoided.Methods and Results: In this prospective randomized study, patients with SVT (atrioventricular re-entrant tachycardia n = 94, typical atrial flutter n = 29) were randomly assigned in a 1:1 ratio to catheter ablation with conventional fluoroscopic guidance (CF group) or with the EnSite Precision mapping system [zerofluoro (ZF) group]. Acute procedural parameters, increased stochastic risk of cancer incidence and 6-month follow-up data were assessed. Between May 2019 and August 2020, 123 patients were enrolled. Clinical parameters were comparable. Median procedural time was 60.0 and 58.0 min, median fluoroscopy time and estimated median effective dose were 240 s vs. 0 and 0.38 mSv vs. 0 and arrhythmia recurrence was 5% and 7.9% in the CF and ZF groups, respectively. The acute success rate was 98.4% in both groups. No procedure-related complications were reported. At an average age of 55.5 years and median radiation exposure of 0.38 mSv, the estimate of increased incidence was approximately 1 in 14 084. The estimated mortality rate was 1 per 17 857 exposed persons.Conclusions: The procedural safety and efficacy of the zero-fluoroscopic approach are similar to those of conventional fluoroscopy-based ablation for atrioventricular nodal re-entrant tachycardia and atrial flutter. Under the assumption of low radiation dose, the excessive lifetime risk of malignancy in the CF group due to electrophysiology procedure is reasonably small, whilst totally reduced in zero fluoroscopy procedures. [ABSTRACT FROM AUTHOR]

Objectives To develop and validate in real-world patients a conversion algorithm from the Multidimensionel Health Assessment Questionnaire physical function scale (MDHAQ) to the Stanford Health Assessment Questionnaire disability index physical function scale (HAQ) score. Methods From the DANBIO registry, 13 391 patients with RA (n  = 8983), PsA (n  = 2649) and axial spondyloarthritis (axSpA, n  = 1759) with longitudinal data on HAQ and MDHAQ were included, stratified by diagnosis, and randomized 1:1 into development and validation cohorts. Conversion algorithms were developed by linear regression and applied in validation cohorts. From MDHAQ, the HAQ was calculated (cHAQ) and validated against the observed HAQ for criterion, correlational and construct validity. Results For RA, we developed the conversion algorithm cHAQ = 0.15+MDHAQ*1.08, and validated it in the RA validation cohort. Criterion validity : HAQ and cHAQ had comparable discriminative power to distinguish between high and low patient global scores (standardized mean difference: HAQ:–1.29, cHAQ:–1.35). Kappa value between HAQ and cHAQ functional states indicated good agreement (0.83). Correlational validity : baseline HAQ and cHAQ, respectively, correlated well with patient global scores (r = 0.65/0.67). Bland–Altman plots showed good agreement across all functional states. Construct validity : HAQ and cHAQ discriminated equally well between patients reporting symptom state as acceptable vs not, and across responses to an external anchor. Aiming for a common algorithm, the RA conversion algorithm was validated for PsA and axSpA with similar results. Conclusion This study suggests that in observational datasets with only the MDHAQ available, a simple algorithm allows valid conversion to HAQ on the group level in RA, PsA and axSpA. [ABSTRACT FROM AUTHOR]

Background We sought to explore multinational differences in functional status by global burden of disease (GBD) regions in the REPRIEVE cohort. Methods REPRIEVE is a prospective, double-blind, randomized, placebo-controlled, multicenter, phase III primary cardiovascular prevention study of pitavastatin calcium vs placebo among people with human immunodeficiency virus (HIV, PWH) ages 40–75 on antiretroviral therapy (ART). GBD super regions were defined using World Health Organization classifications. Participants were categorized by impairment on the Duke Activity Status Instrument (DASI: none, some, moderate, severe). Logistic regression models examined risk factors and GBD regions associated with functional impairment. The association between functional impairment and cardiometabolic risk was also explored. Results Of 7736 participants, the majority were from high-income countries (n = 4065), were male (65%), and had received ART for ≥ 10 years. The median DASI score was 58.2 (interquartile range [IQR] 50.2, 58.2); 36% reported at least some impairment. In adjusted analyses, functional impairment was significantly more frequent among participants from Southeast/East Asia. Other factors associated with greater impairment included female sex, Black race, older age, current/former smoking, higher body mass index, use of ART for ≥ 10 years, and select ART regimens; differences were seen in risks across GBD regions. Functional impairment was associated with increased cardiometabolic risk. Conclusions Over 1/3 of middle-aged and older PWH in a global cohort across diverse GBD regions demonstrate functional impairments. The associations between DASI and cardiometabolic risk suggest that a measure of functional status may improve risk prediction; these longitudinal associations will be further investigated over REPRIEVE trial follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Cerebrospinal fluid (CSF) spectroscopy can identify subarachnoid haemorrhage (SAH) when CT is negative in patients presenting with acute severe headache. The primary objective of this study was to evaluate the clinical use and usefulness of CSF spectrophotometry. Secondary objectives were to identify other causes of elevated CSF bilirubin, to analyse headache descriptions and to compare clinical features in patients with an elevated CSF bilirubin among those with and without an intracranial vascular cause of SAH (avSAH).Methods: Consecutive patients admitted to two hospitals in Enniskillen and Londonderry between 1 January 2004 and 30 September 2014 with CSF spectroscopy bilirubin results were identified from a clinical chemistry laboratory dataset. Patients with elevated CSF bilirubin were studied. Clinical demographics, delays to investigation and final diagnoses were recorded. Patients with avSAH were compared with patients without avSAH.Results: Among 1813 patients with CSF spectrophotometry results, requests increased more than threefold during the study (p<0.001). Fifty-six patients had elevated CSF bilirubin. Ten (17.9%) had avSAH, of which 8 (14.3%) had aneurysmal SAH. Non-vascular causes of elevated CSF bilirubin included meningitis, spontaneous intracranial hypotension and carcinomatous meningitis. Headache descriptions varied. Time from headache onset to admission, CT scan and lumbar puncture did not differ significantly for patients with avSAH and non-avSAH. CSF red cell counts were higher among patients with avSAH than patients with non-avSAH (p=0.005).Conclusions: CSF bilirubin measurement has an important role in identifying avSAH in CT-negative patients presenting with a thunderclap headache. Better clinical selection of patients is required as CSF spectrophotometry, although sensitive, is not specific for SAH. [ABSTRACT FROM AUTHOR]

Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from 8 prospective population-based cohort studies, representing 13 021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had excess mortality from all causes of 57 deaths per 10 000 person-years (95% confidence interval [CI]: 38, 76) compared with their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10 000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the World Health Organization (WHO) risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors. [ABSTRACT FROM AUTHOR]

Aims The hybrid comprehensive telerehabilitation (HCTR) consisting of telecare (with psychological telesupport), telerehabilitation, and remote monitoring of cardiovascular implantable electronic devices might be an option to improve both physical capacity and depressive symptoms. The aim of the study was to investigate the influence of HCTR on depressive symptoms and physical capacity in heart failure (HF) patients in comparison with usual care (UC). Methods and results The present analysis formed part of a multicentre, randomized trial that enrolled 850 HF patients (New York Heart Association I–III, left ventricular ejection fraction ≤ 40%). Patients were randomized 1:1 to HCTR or UC. Patients underwent an HCTR programme (1 week in hospital and 8 weeks at home; exercise training 5 times weekly) or UC with observation. The Beck Depression Inventory II (BDI-II) score (cut point for depression ≥ 14) was used to assess depression and the physical capacity was measured by peak oxygen consumption (peak VO2; mL/kg/min). Measurements were made before and after 9-week intervention/observation (HCTR/UC group). Both groups were comparable in terms of demographic and clinical characteristics. In HCTR group, at entry, 23% of the sample obtained BDI-II scores ≥14 vs. 27.5% in UC group. There were no significant differences between groups regarding ΔBDI-II score (P = 0.992) after 9-week HCTR/UC. There was a significant improvement in physical capacity only in the HCTR group in both patients with (P = 0.033) and without (P < 0.001) depression. Conclusions In HF patients, HCTR provided similar reduction of depressive symptoms as UC. HCTR resulted in a significant improvement in physical capacity in patients with and without depression. [ABSTRACT FROM AUTHOR]

Background: The association between body mass index (BMI) and oesophageal cancer (OC) has been consistently negative among Asians, whereas different associations based on histological OC subtypes have been observed in Europeans and North Americans. We examined the association between BMI and OC mortality in the Asia Cohort Consortium.Methods: We performed a pooled analysis to evaluate the association between BMI and OC mortality among 842 630 Asians from 18 cohort studies. Cox regression models were used to estimate hazard ratios (HRs) and 95% CIs.Results: A wide J-shaped association between BMI and overall OC mortality was observed. The OC mortality risk was increased for underweight (BMI <18.5 kg/m2: HR = 2.20, 95% CI 1.80-2.70) and extreme obesity (BMI ≥35 kg/m2: HR = 4.38, 95% CI 2.25-8.52) relative to the reference BMI (23-25 kg/m2). This association pattern was confirmed by several alternative analyses based on OC incidence and meta-analysis. A similar wide J-shaped association was observed in oesophageal squamous cell carcinoma (OSCC). Smoking and alcohol synergistically increased the OC mortality risk in underweight participants (HR = 6.96, 95% CI 4.54-10.67) relative to that in reference BMI participants not exposed to smoking and alcohol.Conclusion: Extreme obesity and being underweight were associated with an OC mortality risk among Asians. OC mortality and BMI formed a wide J-shaped association mirrored by OSCC mortality. Although the effect of BMI on OSCC and oesophageal adenocarcinoma mortality can be different in Asians, further research based on a large case-control study is recommended. [ABSTRACT FROM AUTHOR]

Study Question: Is there any difference in developmental outcomes in children born after capacitation IVM (CAPA IVM) compared with conventional IVF?Summary Answer: Overall development up to 24 months of age was comparable in children born after CAPA IVM compared with IVF.What Is Known Already: IVM has been shown to be a feasible alternative to conventional IVF in women with a high antral follicle count (AFC). In addition to live birth rate, childhood development is also a relevant metric to compare between the two approaches to ART and there are currently no data on this.Study Design, Size, Duration: This study was a follow-up of babies born to women who participated in a randomized controlled trial comparing IVM with a pre-maturation step (CAPA IVM) and IVF. Developmental assessments were performed on 231 children over 24 months of follow-up.Participants/materials, Setting, Methods: Participants in the randomized controlled trial had an indication for ART and a high AFC (≥24 follicles in both ovaries). They were randomized to undergo one cycle of either IVM (n = 273) or IVF (n = 273). Of these, 96 women and 118 women, respectively, had live births. Seventy-six women (94 children, 79.2%) and 104 women (137 children, 88.1%), respectively, completed Ages & Stages Third Edition Questionnaire assessment (ASQ-3), and underwent evaluation of Developmental Red Flags at 6, 12 and 24 months of age.Main Results and the Role Of Chance: Baseline characteristics of participants in the follow-up study between the IVM and IVF groups were comparable. Overall, there were no significant differences in ASQ-3 scores at 6, 12 and 24 months between children born after IVM or IVF. The proportion of children with developmental red flags was low and did not differ between the two groups. Slightly, but significantly, lower ASQ-3 problem solving and personal-social scores in twins from the IVM versus IVF group at 6 months were still within the normal range and had caught up to the IVF group in the 12- and 24-month assessments. The number of children confirmed to have abnormal mental and/or motor development after specialist assessment was four in the IVM group and two in the IVF group (relative risk 2.91, 95% CI 0.54-15.6; P = 0.23).Limitations, Reasons For Caution: This study is an open-label follow-up of participants in a randomized controlled trial, and not all original trial subjects took part in the follow-up. The self-selected nature of the follow-up population could have introduced bias, and the sample size may have been insufficient to detect significant between-group differences in developmental outcomes.Wider Implications Of the Findings: Based on the current findings at 2 years of follow-up, there does not appear to be any significant concern about the effects of IVM on childhood development. These data add to the evidence available to physicians when considering different approaches to fertility treatment, but require validation in larger studies.Study Funding/competing Interest(s): This work was funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) under grant number FWO.106-YS.2017.02. L.N.V. has received speaker and conference fees from Merck, grant, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring; T.M.H. has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring; R.J.N. has receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia; B.W.M. has acted as a paid consultant to Merck, ObsEva and Guerbet and is the recipient of grant money from an NHMRC Investigator Grant; J.E.J.S. reports lecture fees from Ferring Pharmaceuticals, Biomérieux and Besins Female Healthcare, grants from Fund for Research Flanders (FWO) and is co-inventor on granted patents on CAPA-IVM methodology in the USA (US10392601B2) and Europe (EP3234112B1); T.D.P., M.H.N.N., N.A.N., T.T.L., V.T.T.T., N.T.N., H.L.T.H. and X.T.H.L. have no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work.Trial Registration Number: NCT04296357 (www.clinicaltrials.gov).Trial Registration Date: 5 March 2020.Date Of First Patient’s Enrolment: 7 March 2020. [ABSTRACT FROM AUTHOR]

Background: There is a need for a mortality score that can be used to trigger advanced care planning among older patients discharged from acute geriatric units (AGUs).Objective: We developed a prognostic score for 3- and 12-month mortality after discharge from an AGU, based on a comprehensive geriatric assessment, in-hospital events, and the exclusion of patients already receiving palliative care.Methods: Devenir Après la Médecine Aigue Gériatrique (DAMAGE) is a French multicenter, prospective, cohort study. The broad inclusion criteria ensured that the cohort is representative of patients treated in an AGU. The DAMAGE participants underwent a comprehensive geriatric assessment, a daily clinical checkup, and follow-up visits 3 and 12 months after discharge. Multivariable logistic regression models were used to develop a prognostic score for the derivation and validation subsets.Results: A total of 3 509 patients were assessed and 3 112 were included. The patient population was very old and frail or dependant, with a high proportion of deaths at 3 months (n = 455, 14.8%) and at 12 months (n = 1 014, 33%). The score predicted an individual risk of mortality ranging from 1% to 80% at 3 months and between 5% and 93% at 12 months, with an area under the receiving operator characteristic curve in the validation cohort of 0.728 at 3 months and 0.733 at 12 months.Conclusions: Our score predicted a broad range of risks of death after discharge from the AGU. Having this information at the time of hospital discharge might trigger a discussion on advanced care planning and end-of-life care with very old, frail patients. Clinical Trials Registration Number: NCT02949635. [ABSTRACT FROM AUTHOR]

Purpose: Shared medical appointments (SMAs) may help mitigate some of the barriers for managing obesity in primary care. The primary aim of this systematic review was to measure the effect of weight loss SMAs.Methods: Systematic searches using keywords and Medical Subject Headings for overweight, obesity, and SMAs were conducted in the CENTRAL, Medline Complete, PsycINFO, Scopus, CINAHL, EMBASE, and Web of Science databases with no date limits. Risk of bias was assessed using the Effective Health Practice Project Quality Assessment Tool for Quantitative Studies.Results: Fifteen studies involving weight loss SMAs in adults and children were identified. Six studies had controls. Inconsistency in reporting weight loss or weight change in controlled studies meant that data could not be pooled for meta-analysis. Results from individual studies indicated that SMAs can support adult patients to achieve significant weight loss. Women and older adults were more likely to take up SMA invitations. Results from the 5 studies involving children were less conclusive. Studies involving participants of a higher socioeconomic status tended to report lower attrition than studies involving participants who experienced disadvantage. These findings should be interpreted with caution as all but 1 included study was assessed as being weak in quality.Conclusions: Overall, SMAs may be of benefit to address obesity in primary care, particularly for women and older adults. Appropriately designed prospective and controlled studies are required to engage their target audience and to assess whether SMAs are superior to other weight loss options in primary care. [ABSTRACT FROM AUTHOR]

Background The impact of the US Centers for Medicare & Medicaid Services (CMS) Severe Sepsis and Septic Shock: Management Bundle (SEP-1) core measure on overall antibacterial utilization is unknown. Methods We performed a retrospective multicenter longitudinal cohort study with interrupted time–series analysis to determine the impact of SEP-1 implementation on antibacterial utilization and patient outcomes. All adult patients admitted to 26 hospitals between 1 October 2014 and 30 September 2015 (SEP-1 preparation period) and between 1 November 2015 and 31 October 2016 (SEP-1 implementation period) were evaluated for inclusion. The primary outcome was total antibacterial utilization, measured as days of therapy (DOT) per 1000 patient-days. Results The study cohort included 701 055 eligible patient admissions and 4.2 million patient-days. Overall antibacterial utilization increased 2% each month during SEP-1 preparation (relative rate [RR], 1.02 per month [95% confidence interval {CI}, 1.00–1.04]; P =.02). Cumulatively, the mean monthly DOT per 1000 patient-days increased 24.4% (95% CI, 18.0%–38.8%) over the entire study period (October 2014–October 2016). The rate of sepsis diagnosis/1000 patients increased 2% each month during SEP-1 preparation (RR, 1.02 per month [95% CI, 1.00–1.04]; P =.04). The rate of all-cause mortality rate per 1000 patients decreased during the study period (RR for SEP-1 preparation, 0.95 [95% CI,.92–.98; P =.001]; RR for SEP-1 implementation,.98 [.97–1.00; P =.01]). Cumulatively, the monthly mean all-cause mortality rate/1000 patients declined 38.5% (95% CI, 25.9%–48.0%) over the study period. Conclusions Announcement and implementation of the CMS SEP-1 process measure was associated with increased diagnosis of sepsis and antibacterial utilization and decreased mortality rate among hospitalized patients. [ABSTRACT FROM AUTHOR]

Objectives: To describe current resistance to the β-lactams empirically recommended in the guidelines in bloodstream infection (BSI) episodes caused by Gram-negative bacilli (GNB).Methods: Retrospective, multicentre cohort study of the last 50 BSI episodes in haematological patients across 14 university hospitals in Spain. Rates of inappropriate empirical antibiotic therapy (IEAT) and impact on mortality were evaluated.Results: Of the 700 BSI episodes, 308 (44%) were caused by GNB, mainly Escherichia coli (141; 20.1%), Klebsiella spp. (56; 8%) and Pseudomonas aeruginosa (48; 6.9%). Among GNB BSI episodes, 80 (26%) were caused by MDR isolates. In those caused by Enterobacterales, 25.8% were ESBL producers and 3.5% were carbapenemase producers. Among P. aeruginosa BSI episodes, 18.8% were caused by MDR isolates. Overall, 34.7% of the isolated GNB were resistant to at least one of the three β-lactams recommended in febrile neutropenia guidelines (cefepime, piperacillin/tazobactam and meropenem). Despite extensive compliance with guideline recommendations (91.6%), 16.6% of BSI episodes caused by GNB received IEAT, which was more frequent among MDR GNB isolates (46.3% versus 6.1%; P < 0.001). Thirty day mortality was 14.6%, reaching 21.6% in patients receiving IEAT.Conclusions: Current resistance to empirical β-lactams recommended in febrile neutropenia guidelines is exceedingly high and IEAT rates are greater than desired. There is an urgent need to adapt guidelines to current epidemiology and better identify patients with a high risk of developing MDR GNB infection. [ABSTRACT FROM AUTHOR]