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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]

A large number of observational studies have found a J-shaped relationship between alcohol intake and ischemic heart disease (IHD) risk. However, some studies suggest that the alleged cardio-protective effect may be an artifact in the way that the elevated risk for abstainers is due to self-selection on risk factors for IHD. The aim of this paper is to estimate the association between alcohol and IHD-mortality on the basis of aggregate time-series data, where the problem with selection effects is not present. In addition, we will analyze SES-specific mortality to investigate whether there is any socio-economic gradient in the relationship at issue. SES was measured by educational level. We used IHD-mortality in three educational groups as outcome. Per capita alcohol consumption was proxied by Systembolaget's alcohol sales (litres of alcohol 100% per capita 15+). Swedish quarterly data on mortality and alcohol consumption spanned the period 1991Q1–2020Q4. We applied SARIMA time-series analysis. Survey data were used to construct an indicator of heavy SES-specific episodic drinking. The estimated association between per capita consumption and IHD-mortality was positive and statistically significant in the two groups with primary and secondary education, but not in the group with postsecondary education. The association was significantly stronger the lower the educational group. Although the associations were generally stronger for males than for females, these differences were not statistically significant (P  > 0.05). Our findings suggest that the detrimental impact of per capita consumption on IHD-mortality was stronger the lower the educational group. [ABSTRACT FROM AUTHOR]

Background This paper presents the results of an exercise to scope the potential of a virtual network to support dissemination, collaboration and innovation among the UK research community on the topic of 'work and health and well-being'. Methods Through a search of the literature and internet searches, a database of 333 individuals and 10 organizations (stakeholders) was developed to whom an online questionnaire was sent. The questionnaire scoped the potential of a virtual network on work and health and well- being. We compared respondents' aspirations for a network with the critical management literature examining the core conditions under which networks work best. Results We identified 1435 papers, published since 2008. In the UK, 333 individuals and 10 organizations were identified as working within the broad topic of Work and Health and Well-being. Of the 110 (a 34% response) responses to our online questionnaire, the majority (80%, n = 88) stated they would be interested in joining a virtual network. Conclusions Respondents indicated a willingness to engage with the network. They had a range of ideas regarding how a network could operate, which broadly match the conditions that support network effectiveness. A virtual-enabled network would be best supplemented by opportunities for face-to-face interaction. [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: the care of older people with dementia is often complicated by physical comorbidity and polypharmacy, but the extent and patterns of these have not been well described. This paper reports analysis of these factors within a large, cross-sectional primary care data set. Methods: data were extracted for 291,169 people aged 65 years or older registered with 314 general practices in the UK, of whom 10,258 had an electronically recorded dementia diagnosis. Differences in the number and type of 32 physical conditions and the number of repeat prescriptions in those with and without dementia were examined. Age-gender standardised rates were used to calculate odds ratios (ORs) of physical comorbidity and polypharmacy. Results: people with dementia, after controlling for age and sex, had on average more physical conditions than controls (mean number of conditions 2.9 versus 2.4; P < 0.001) and were on more repeat medication (mean number of repeats 5.4 versus 4.2; P < 0.001). Those with dementia were more likely to have 5 or more physical conditions (age-sex standardised OR [sOR] 1.42, 95% confidence interval (CI) 1.35-1.50; P < 0.001) and were also more likely to be on 5 or more (sOR 1.46; 95% CI 1.40-1.52; P < 0.001) or 10 or more repeat prescriptions (sOR 2.01; 95% CI 1.90-2.12; P < 0.001). Conclusions: people with dementia have a higher burden of comorbid physical disease and polypharmacy than those without dementia, even after accounting for age and sex differences. Such complex needs require an integrated response from general health professionals and multidisciplinary dementia specialists. [ABSTRACT FROM AUTHOR]

Background With the rapid development of the global economy and the acceleration of urbanization, air pollution has become a major environmental problem threatening human health. There is limited evidence on the acute effects of air pollution on chronic obstructive pulmonary disease (COPD). Methods From 2014 to 2019, we collected data on daily admissions for COPD patients from a city in China. We used the generalized additive model together with distributed lag models to fit the associations of air pollutants with hospital admissions. Results We observed significant increments in the number of daily admissions (0.086–0.109%) for COPD for a unit range increase in air quality index, PM 2.5 and PM 10 over four lag days. The impact of air pollution on the number of daily admissions was mainly reflected in the COPD patients who were hospitalized through outpatient departments and tertiary hospitals. Discussion Short-term exposure to outdoor air pollution may induce the occurrence or exacerbation of COPD patients; therefore, government departments should strengthen the management of air pollution, improve supervision and control mechanisms, pay attention to the quality of medical services, and reduce the adverse effects of air pollution on patients' health. [ABSTRACT FROM AUTHOR]

Explicit criteria, such as the STOPP/START criteria, are increasingly used both in clinical practice and in research to identify potentially inappropriate prescribing in older people. In an article on the STOPP/START criteria version 2, O'Mahony et al. have pointed out the advantages of developing computerised criteria. Both clinical decision support systems to support healthcare professionals and software applications to automatically detect inappropriate prescribing in research studies can be developed. In the process of developing such tools, difficulties may occur. In the context of a research study, we have developed an algorithm to automatically apply STOPP/START criteria version 2 to our research database. We comment in this paper on different kinds of difficulties encountered and make suggestions that could be taken into account when developing the next version of the criteria. [ABSTRACT FROM AUTHOR]

Clinical and research staff who work around magnetic resonance imaging (MRI) scanners are exposed to the static magnetic stray fields of these scanners. Although the past decade has seen strong developments in the assessment of occupational exposure to electromagnetic fields from MRI scanners, there is insufficient insight into the exposure variability that characterizes routine MRI work practice. However, this is an essential component of risk assessment and epidemiological studies. This paper describes the results of a measurement survey of shift-based personal exposure to static magnetic fields (SMF) (B) and motion-induced time-varying magnetic fields (dB/dt) among workers at 15 MRI facilities in the Netherlands. With the use of portable magnetic field dosimeters, >400 full-shift and partial shift exposure measurements were collected among various jobs involved in clinical and research MRI. Various full-shift exposure metrics for B and motion-induced dB/dt exposure were calculated from the measurements, including instantaneous peak exposure and time-weighted average (TWA) exposures. We found strong correlations between levels of static (B) and time-varying (dB/dt) exposure (r = 0.88–0.92) and between different metrics (i.e. peak exposure, TWA exposure) to express full-shift exposure (r = 0.69–0.78). On average, participants were exposed to MRI-related SMFs during only 3.7% of their work shift. Average and peak B and dB/dt exposure levels during the work inside the MRI scanner room were highest among technical staff, research staff, and radiographers. Average and peak B exposure levels were lowest among cleaners, while dB/dt levels were lowest among anaesthesiology staff. Although modest exposure variability between workplaces and occupations was observed, variation between individuals of the same occupation was substantial, especially among research staff. This relatively large variability between workers with the same job suggests that exposure classification based solely on job title may not be an optimal grouping strategy for epidemiological purposes. [ABSTRACT FROM AUTHOR]

The aim of this study was to update and validate the Pregnancy Physical Activity Questionnaire (PPAQ), using novel and innovative accelerometer and wearable camera measures in a free-living setting, to improve the measurement performance of this method for self-reporting physical activity. A prospective cohort of 50 eligible pregnant women were enrolled in early pregnancy (mean = 14.9 weeks' gestation). In early, middle, and late pregnancy, participants completed the updated PPAQ and, for 7 days, wore an accelerometer (GT3X-BT; ActiGraph, Pensacola, Florida) on the nondominant wrist and a wearable camera (Autographer; OMG Life (defunct)). At the end of the 7-day period, participants repeated the PPAQ. Spearman correlations between the PPAQ and accelerometer data ranged from 0.37 to 0.44 for total activity, 0.17 to 0.53 for moderate- to vigorous-intensity activity, 0.19 to 0.42 for light-intensity activity, and 0.23 to 0.45 for sedentary behavior. Spearman correlations between the PPAQ and wearable camera data ranged from 0.52 to 0.70 for sports/exercise and from 0.26 to 0.30 for transportation activity. Reproducibility scores ranged from 0.70 to 0.92 for moderate- to vigorous-intensity activity and from 0.79 to 0.91 for sports/exercise, and were comparable across other domains of physical activity. The PPAQ is a reliable instrument and a valid measure of a broad range of physical activities during pregnancy. [ABSTRACT FROM AUTHOR]

Objective To investigate the prevalence and mortality impact of interstitial lung abnormalities (ILAs) in RA and non-RA comparators. Methods We analysed associations between ILAs, RA, and mortality in COPDGene, a multicentre prospective cohort study of current and past smokers, excluding known interstitial lung disease (ILD) or bronchiectasis. All participants had research chest high-resolution CT (HRCT) reviewed by a sequential reading method to classify ILA as present, indeterminate or absent. RA cases were identified by self-report RA and DMARD use; non-RA comparators had neither an RA diagnosis nor used DMARDs. We examined the association and mortality risk of RA and ILA using multivariable logistic regression and Cox regression. Results We identified 83 RA cases and 8725 non-RA comparators with HRCT performed for research purposes. ILA prevalence was 16.9% in RA cases and 5.0% in non-RA comparators. After adjusting for potential confounders, including genetics, current/past smoking and other lifestyle factors, ILAs were more common among those with RA compared with non-RA [odds ratio 4.76 (95% CI 2.54, 8.92)]. RA with ILAs or indeterminate for ILAs was associated with higher all-cause mortality compared with non-RA without ILAs [hazard ratio (HR) 3.16 (95% CI 2.11, 4.74)] and RA cases without ILA [HR 3.02 (95% CI 1.36, 6.75)]. Conclusions In this cohort of smokers, RA was associated with ILAs and this persisted after adjustment for current/past smoking and genetic/lifestyle risk factors. RA with ILAs in smokers had a 3-fold increased all-cause mortality, emphasizing the importance of further screening and treatment strategies for preclinical ILD in RA. [ABSTRACT FROM AUTHOR]

Background and Hypotheses Several biological markers are believed to reflect accelerated aging in schizophrenia spectrum disorders; however, retinal neural changes have not yet been explored as potential CNS biomarkers of accelerated aging in this population. The aim of this study was to determine whether retinal neural layer thinning is more strongly related to age in schizophrenia and schizoaffective disorder patients (SZ) than in a psychiatrically healthy control group (CON). Study Design Schizophrenia (n = 60) and CON participants (n = 69) underwent spectral domain optical coherence tomography (OCT) scans to examine the following variables in both eyes: retinal nerve fiber layer (RNFL) thickness, macula central subfield (CSF) thickness, macula volume, ganglion cell layer-inner plexiform layer (GCL-IPL) thickness, optic cup volume, and cup-to-disc ratio. Eleven participants in each group had diabetes or hypertension. Study Results Significant negative relationships between age and RNFL thickness, macula volume, and GCL-IPL thickness were observed in the SZ group, while no significant relationships were observed in the CON group. However, many of the findings in the SZ group lost significance when participants with diabetes/hypertension were removed from analyses. A notable exception to this was that the age × SZ interaction accounted for a unique proportion of variance in GCL-IPL thinning over and above the effect of diabetes/hypertension. Conclusions The results suggest that retinal atrophy occurs at an increased rate in schizophrenia spectrum disorders, potentially reflecting accelerated aging inherent to these conditions, with considerable contributions from systemic medical diseases closely linked to this population. [ABSTRACT FROM AUTHOR]

Background Intelligent artificial agents ('agents') have emerged in various domains of human society (healthcare, legal, social). Since using intelligent agents can lead to biases, a common proposed solution is to keep the human in the loop. Will this be enough to ensure unbiased decision making? Methods To address this question, an experimental testbed was developed in which a human participant and an agent collaboratively conduct triage on patients during a pandemic crisis. The agent uses data to support the human by providing advice and extra information about the patients. In one condition, the agent provided sound advice; the agent in the other condition gave biased advice. The research question was whether participants neutralized bias from the biased artificial agent. Results Although it was an exploratory study, the data suggest that human participants may not be sufficiently in control to correct the agent's bias. Conclusions This research shows how important it is to design and test for human control in concrete human–machine collaboration contexts. It suggests that insufficient human control can potentially result in people being unable to detect biases in machines and thus unable to prevent machine biases from affecting decisions. [ABSTRACT FROM AUTHOR]

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]

Background There is limited knowledge of whether cognitive-behavioral therapy (CBT) or second-generation antipsychotics (SGAs) should be recommended as the first-line treatment in individuals at clinical high risk for psychosis (CHRp). Hypothesis To examine whether individual treatment arms are superior to placebo and whether CBT is non-inferior to SGAs in preventing psychosis over 12 months of treatment. Study Design PREVENT was a blinded, 3-armed, randomized controlled trial comparing CBT to clinical management plus aripiprazole (CM + ARI) or plus placebo (CM + PLC) at 11 CHRp services. The primary outcome was transition to psychosis at 12 months. Analyses were by intention-to-treat. Study Results Two hundred eighty CHRp individuals were randomized: 129 in CBT, 96 in CM + ARI, and 55 in CM + PLC. In week 52, 21 patients in CBT, 19 in CM + ARI, and 7 in CM + PLC had transitioned to psychosis, with no significant differences between treatment arms (P  = .342). Psychopathology and psychosocial functioning levels improved in all treatment arms, with no significant differences. Conclusions The analysis of the primary outcome transition to psychosis at 12 months and secondary outcomes symptoms and functioning did not demonstrate significant advantages of the active treatments over placebo. The conclusion is that within this trial, neither low-dose aripiprazole nor CBT offered additional benefits over clinical management and placebo. [ABSTRACT FROM AUTHOR]

Respondent-driven sampling (RDS) is a potential strategy for addressing challenges in accurate estimation of abortion incidence, but it relies on often untested assumptions. We conducted an RDS study to estimate the cumulative lifetime incidence of abortion in Soweto, Johannesburg, South Africa (April–December 2018), to evaluate whether RDS assumptions were met, and to compare RDS estimates of incidence with estimates adjusted for employment and age based on census data. A total of 849 participants were recruited from 11 seed participants between April and December 2018. The assumption that individuals can identify target population members and the assumption of approximation of sampling with replacement was met. There were minor violations of the assumptions of seed independence from the final sample and reciprocity of ties. Assumptions of accurate degree reporting and random recruitment were not met. Failure to meet assumptions yielded a study sample with different employment characteristics than those of the target population; this could not be resolved by standard RDS methods. The RDS estimate of cumulative lifetime abortion incidence was 12.1% (95% confidence interval: 9.8, 14.3), and the employment-adjusted estimate was 16.9% (95% confidence interval: 12.8, 22.1). We caution researchers in using RDS for representative estimates of abortion incidence. Use of postsurvey weights to adjust for differences in characteristics between the sample and the target population may yield more representative results. [ABSTRACT FROM AUTHOR]

We describe a new method for presenting and interpreting linear trends in health inequalities, and present a proof-of-concept analysis of inequalities in smoking among adolescents in Europe. We estimated the regression line of the assumed linear relationship between smoking prevalence in low– and high–socioeconomic status (SES) youth over time. Using simulation, we constructed a 95% confidence interval (CI) for the smoking prevalence in low-SES youth for when this would be 0% in high-SES youth, and we calculated the likelihood of eradicating smoking inequality (<5% for both low and high SES). This method was applied to data on adolescents aged 15–16 years (n  = 250,326) from 23 European countries, derived from the 2003–2015 European Survey Project on Alcohol and Other Drugs. Smoking prevalence decreased more slowly among low- than among high-SES adolescents. The estimated smoking prevalence was 9.4% (95% CI: 6.1, 12.7) for boys and 5.4% (95% CI: 1.4, 9.2) for girls with low SES when 0% with high SES. The likelihood of eradicating smoking inequality was <1% for boys and 37% for girls. We conclude that this novel methodological approach to trends in health inequalities is feasible in practice. Applying it to trends in smoking inequalities among adolescents in Europe, we found that Europe is currently not on track to eradicate youth smoking across SES groups. [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]

Background There is a lack of consensus regarding the optimal method of assessing health-related quality of life (HR-QOL) among patients with metastatic renal cell carcinoma (mRCC). This study explored the perceived relevance of items that make up the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), as judged by patients with mRCC. Methods This was a multinational cross-sectional survey. Eligible patients responded to a questionnaire composed of 18 items that assessed the perceived relevance of each item in the FKSI-19 questionnaire. Open-ended questions assessed additional issues deemed relevant by patients. Responses were grouped as relevant (scores 2-5) or nonrelevant (score 1). Descriptive statistics were collated, and open-ended questions were analyzed and categorized into descriptive categories. Spearman correlation statistics were used to test the association between relevance and clinical characteristics. Results A total of 151 patients were included (gender: 78.1 M, 21.9F; median age: 64; treatment: 38.4 immunotherapy, 29.8 targeted therapy, 13.9 immuno-TKI combination therapy) in the study. The most relevant questions evaluated fatigue (77.5), lack of energy (72.2), and worry that their condition will get worse (71.5). Most patients rated blood in urine (15.2), fevers (16.6), and lack of appetite (23.2) as least relevant. Qualitative analysis of open-ended questions revealed several themes, including emotional and physical symptoms, ability to live independently, effectiveness of treatment, family, spirituality, and financial toxicity. Conclusion There is a need to refine widely used HR-QOL measures that are employed among patients diagnosed with mRCC treated with contemporary therapies. Guidance was provided for the inclusion of more relevant items to patients' cancer journey. [ABSTRACT FROM AUTHOR]

Objectives Previous systematic reviews focused on the evidence of common risk factors for knee OA (KOA); however, the effect and strength of association between risk factors and KOA might be different between the two sexes. The aim of the present systematic review was to determine the current evidence on sex differences in the association between risk factors and KOA and their prevalence. Methods We searched the following electronic bibliographic databases: MEDLINE (PubMed), EMBASE and Web of Science. A methodological quality assessment was conducted independently by two researchers according to an adapted version of the standardized set of criteria known as the Newcastle-Ottawa Quality Assessment Scale (NOS). The NOS, a star system, was converted to three categories of quality. Results In total, 27 studies reported sex-specific risk estimates on several risk factors for KOA. Out of the 22 longitudinal cohort studies (except one nested case–control), 12 were of good quality and 10 were of fair quality. The five cross-sectional studies consisted of one of good, three of fair and one of poor quality. There was an indication of sex differences in risk factors leading to higher risk of KOA: high BMI, alcohol consumption, atherosclerosis and high vitamin E levels in women, and high physical activity, soft drink consumption and abdominal obesity in men. Knee injury, high blood pressure and low step rate seem to affect both women and men. Conclusion More good quality studies are needed to assess sex differences in risk factors for KOA, especially for symptomatic/clinical OA. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Cognitive remediation (CR) benefits cognition and functioning in psychosis but we do not know the optimal level of therapist contact, so we evaluated the potential benefits of different CR modes. Study Design A multi-arm, multi-center, single-blinded, adaptive trial of therapist-supported CR. Participants from 11 NHS early intervention psychosis services were independently randomized to Independent, Group, One-to-One, or Treatment-as-usual (TAU). The primary outcome was functional recovery (Goal Attainment Scale [GAS]) at 15-weeks post randomization. Independent and TAU arms were closed after an interim analysis, and three informative contrasts tested (Group vs One-to-One, Independent vs TAU, Group + One-to-One vs TAU). Health economic analyses considered the cost per Quality Adjusted Life Year (QALY). All analyses used intention-to-treat principles. Study Results We analyzed 377 participants (65 Independent, 134 Group, 112 One-to-One, 66 TAU). GAS did not differ for Group vs One-to-One: Cohen's d : 0.07, −0.25 to 0.40 95% CI, P  = .655; Independent vs TAU: Cohen's d : 0.07, −0.41 to 0.55 95% CI, P  = .777. GAS and the cognitive score improved for Group + One-to-One vs TAU favoring CR (GAS: Cohen's d : 0.57, 0.19–0.96 95% CI, P  = .003; Cognitive score: Cohens d : 0.28, 0.07–0.48 95% CI, P  = .008). The QALY costs were £4306 for Group vs TAU and £3170 for One-to-One vs TAU. Adverse events did not differ between treatment methods and no serious adverse events were related to treatment. Conclusions Both active therapist methods provided cost-effective treatment benefiting functional recovery in early psychosis and should be adopted within services. Some individuals benefited more than others so needs further investigation. Trial registration ISRCTN14678860 https://doi.org/10.1186/ISRCTN14678860 Now closed. [ABSTRACT FROM AUTHOR]

Aims Magnetic resonance spectroscopy (MRS) has been used to probe inflammation in the brain. While altered MRS metabolite levels have previously been found in individuals with alcohol use disorder (AUD), the relationship between potential metabolite markers of inflammation and the clinical correlates of AUD remains understudied. Therefore, this exploratory study sought to elucidate the clinical significance of inflammation in AUD by examining relationships between metabolites, AUD severity, alcohol consumption, and craving in individuals with AUD. Methods Data for this secondary analysis are derived from a two-week clinical trial of ibudilast to treat AUD. Forty-three non-treatment-seeking individuals with an AUD (26M/17F) completed an MRS scan and alcohol-related questionnaires. MRS was performed using a multi-voxel array placed above the corpus callosum, extending from the pregnenual anterior cingulate to premotor cortex. The dorsal anterior cingulate was selected as the volume of interest. Metabolite levels of choline-compounds (Cho), myo -inositol (mI), and creatine+phosphocreatine (Cr) were quantified. Separate hierarchical regression models were used to evaluate the independent effects of metabolite levels on alcohol craving, alcohol problem severity, and alcohol consumption. Results Dorsal anterior cingulate Cho predicted alcohol craving and alcohol problem severity over and above demographics, medication, and alcohol consumption measures. mI and Cr did not predict alcohol craving or alcohol problem severity. Metabolite markers were not predictive of alcohol consumption. Conclusions This preliminary study indicates that dACC Cho is sensitive to clinical characteristics of AUD. This is a further step in advancing neurometabolites, particularly Cho, as potential biomarkers and treatment targets for AUD. [ABSTRACT FROM AUTHOR]

Background The consequences of financial crises on patients' use of healthcare have been widely discussed. This paper seeks to ascertain whether the position of key players, i.e. doctors, may reveal realities other than those officially reported about the 2008 financial crisis. Methods In 2013-14, a national survey of doctors was conducted in Portugal, which received international assistance in the wake of the financial crisis. An exploratory model comprising descriptive statistics, regression and independence analyses focused on doctors' experience of patients' use of medications, consultations, exams and treatment services, and whether they stopped treatments. Results According to doctors, an unspecified number of patients experienced difficulties using healthcare as more patients requested prescriptions for cheaper medications or simply stopped treatments. Significant variations were found according to speciality, years of practice and sector of activity. Conclusions Cost-containment mechanisms are regarded as necessary. However, the evidence indicated a side effect, i.e. a decrease in patients' ability to use healthcare, including in the National Health Service (NHS). It also highlighted the need to listen to health professionals as key informants on patient's behaviour and the daily functioning of health services. [ABSTRACT FROM AUTHOR]

Objective. A comprehensive electronic self-report assessment, called PainCAS1® (Clinical Assessment System), was developed and implemented in three clinics. PainCAS captures demographic information, pain assessment, quality-of-life variables, and contains validated, electronic versions of screeners for risk of aberrant opioid-related behaviors (the SOAPP and COMM). This investigation sought to determine the impact of PainCAS on documentation of pain and opioid risk evaluations. Exploratory hypotheses examined changes in the content of the patient-provider interaction and any impact on outcome. Methods. In study 1, chart reviews were conducted between pain patients who completed the electronic program (N = 89) and controls who represented standard of care (N = 120). In study 2, two groups of chronic pain patients (treatment-as-usual Control condition = 75, PainCAS Experimental condition = 72) were interviewed after completing their index clinic visit and completed mailed questionnaires 3 months later. Results. Results revealed significantly more key, pain-relevant chart elements documented in charts of patients who completed the PainCAS than those using a traditional paper questionnaire (Study 1; <0.001). In Study 2, the Experimental group reported more discussion about legal issues, substance use history, and medication safety compared with the Control group (p<0.05). Satisfaction questionnaire responses supported provider and patient perceived benefit from using PainCAS. However, as expected, no differences were found between conditions on outcome measures of pain, mood, and function. Conclusions. Results indicate that use of the PainCAS electronic pain assessment improves documentation of chart elements in clinic notes and is associated with increased discussion of key, painrelevant topics during the clinical visit. [ABSTRACT FROM AUTHOR]

Objective Parotid swelling (PSW) is a major predictor of non-Hodgkin's lymphoma (NHL) in primary SS (pSS). However, since detailed information on the time of onset and duration of PSW is scarce, this was investigated to verify whether it may lead to further improved prediction. NHL localization was concomitantly studied to evaluate the role of the parotid gland microenvironment in pSS-related lymphomagenesis. Methods A multicentre study was conducted among patients with pSS who developed B cell NHL during follow-up and matched controls that did not develop NHL. The study focused on the history of salivary gland and lachrymal gland swelling, evaluated in detail at different times and for different durations, and on the localization of NHL at onset. Results PSW was significantly more frequent among the cases: at the time of first referred pSS symptoms before diagnosis, at diagnosis and from pSS diagnosis to NHL. The duration of PSW was evaluated starting from pSS diagnosis, and the NHL risk increased from PSW of 2–12 months to >12 months. NHL was prevalently localized in the parotid glands of the cases. Conclusion A more precise clinical recording of PSW can improve lymphoma prediction in pSS. PSW as a very early symptom is a predictor, and a longer duration of PSW is associated with a higher risk of NHL. Since lymphoma usually localizes in the parotid glands, and not in the other salivary or lachrymal glands, the parotid microenvironment appears to be involved in the whole history of pSS and related lymphomagenesis. [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]

Background There is a need for effective primary care interventions that help older people combat frailty and build resilience. Objective To study the effectiveness of an optimised exercise and dietary protein intervention. Design Multicentre, randomised-controlled, parallel-arm trial. Setting Six primary care practices, Ireland. Methods Six general practitioners enrolled adults aged 65+ with Clinical Frailty Scale score ≤5 from December 2020 to May 2021. Participants were randomised to intervention or usual care with allocation concealed until enrolment. Intervention comprised a 3-month home-based exercise regime, emphasising strength, and dietary protein guidance (1.2 g/kg/day). Effectiveness was measured by comparing frailty levels, based on the SHARE-Frailty Instrument, on an intention-to-treat basis. Secondary outcomes included bone mass, muscle mass and biological age measured by bioelectrical impedance analysis. Ease of intervention and perceived health benefit were measured on Likert scales. Results Of the 359 adults screened, 197 were eligible and 168 enrolled; 156 (92.9%) attended follow-up (mean age 77.1; 67.3% women; 79 intervention, 77 control). At baseline, 17.7% of intervention and 16.9% of control participants were frail by SHARE-FI. At follow-up, 6.3 and 18.2% were frail, respectively. The odds ratio of being frail between intervention and control groups post-intervention was 0.23 (95% confidence interval: 0.07–0.72; P  = 0.011), adjusting for age, gender and site. Absolute risk reduction was 11.9% (CI: 0.8%–22.9%). Number needed to treat was 8.4. Grip strength (P  < 0.001) and bone mass (P  = 0.040) improved significantly. 66.2% found the intervention easy, 69.0% reported feeling better. Conclusion A combination of exercises and dietary protein significantly reduced frailty and improved self-reported health. [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]

Objectives To investigate the reliability of the OMERACT US Task Force definition of US enthesitis in SpA. Methods In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA (hypoechoic areas, entheseal thickening, power Doppler signal at the enthesis, enthesophytes/calcifications, bone erosions) were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter- and intra-observer reliability of the US components of enthesitis was calculated using Light's kappa, Cohen's kappa, Prevalence And Bias Adjusted Kappa (PABAK) and their 95% CIs. Results Bone erosions and power Doppler signal at the enthesis showed the highest overall inter-reliability [Light's kappa: 0.77 (0.76–0.78), 0.72 (0.71–0.73), respectively; PABAK: 0.86 (0.86–0.87), 0.73 (0.73–0.74), respectively], followed by enthesophytes/calcifications [Light's kappa: 0.65 (0.64–0.65), PABAK: 0.67 (0.67–0.68)]. This was moderate for entheseal thickening [Light's kappa: 0.41 (0.41–0.42), PABAK: 0.41 (0.40–0.42)], and fair for hypoechoic areas [Light's kappa: 0.37 (0.36–0.38); PABAK: 0.37 (0.37–0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation. Conclusions The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, power Doppler signal at the enthesis and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis. [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]

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 Most households may have leftover, unwanted, unused and expired (UUE) medicines. The present research aimed to analyze feasibility of implementation of medicine take-back in select communities in Nepal. Methods Exploratory (i.e. feasibility) study was conducted among 400 adults from July 2017 to January 2018. Study sites and participants were selected by simple random sampling and respondents were interviewed about their awareness about medicine disposal, hazards and willingness to support take-back program using semi-structured questionnaire. Multinomial logistic regression analysis was applied to explore relationship of take-back related outcomes with the predictors. The P -value < 0.05 was statistically significant at 95% confidence level. Results Land pollution and effect on health of children was significantly related with inappropriate disposal of medicines such as site of disposal (P value < 0.01), river (P value, 0.02), garbage (P value, 0.04) and dumping site (P value, 0.01). Analysis of willingness to follow take-back program with the techniques of support showed significant relationship with the establishment of collection center and participation on seminar (P value < 0.01). Conclusion Most participants were interested to support take-back, if implemented in their community but main constraint was the budget. Take-back concept could be initiated and implemented on government funding or other sources. [ABSTRACT FROM AUTHOR]

The Healthy Change Program aimed to improve the accuracy of maternal perceptions of children's weight (MPCW), maternal feeding style (MFS) and feeding practices. Using a randomized control trial design, the intervention group received 4-weekly group sessions focusing on MPCW, MFS and healthy behaviors. The control group received the same dose of attention-control sessions on food hygiene. Data were collected at the baseline and at the end of the program via self-administered questionnaires and anthropometric measurements. Participants included 294 mother–child dyads with 149 in the intervention group and 145 in the control group. The accuracy of MPCW significantly increased at the study end point in the intervention group (57.0–67.1%, P  < 0.05) but not in the control group (67.6–69.7%, P  > 0.05), with no between-group difference in pre- and post-change (P  > 0.05). At the study end point, more mothers of overweight and obese children in the intervention group had accurate MPCW than their control counterparts (31.4% versus 11.1%, P  < 0.01). The intervention group had a shift toward an authoritative style at the study end point (17.4% versus 26.2%, P  < 0.001) and favorable changes in feeding practices. The Healthy Change Program contributed to improving the accuracy of MPCW and shifts toward favorable MFS and feeding practices. [ABSTRACT FROM AUTHOR]

Background age-adapted definition of chronic kidney disease (CKD) does not take individual risk factors into account. We aimed at investigating whether functional impairments influence CKD stage at which mortality increases among older people. Methods our series consisted of 2,372 outpatients aged 75 years or more enrolled in a multicentre international prospective cohort study. The study outcome was 24-month mortality. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). Geriatric assessments included handgrip strength, short physical performance battery (SPPB), cognitive impairment, dependency in basic activities of daily living (BADL) and risk of malnutrition. Analysis was carried out by Cox regression, before and after stratification by individual functional impairments. Survival trees including kidney function and functional impairments were also investigated, and their predictivity assessed by C-index. Results overall, mortality was found to increase starting from eGFR = 30–44.9 ml/min/1.73 m2 (hazard ratio [HR] = 3.28, 95% confidence interval [CI] = 1.81–5.95) to ACR = 30–300 mg/g (HR = 1.96, 95%CI = 1.23–3.10). However, in survival trees, an increased risk of mortality was observed among patients with impaired handgrip and eGFR = 45–59.9 ml/min/1.73 m2, as well as patients with ACR < 30 mg/g and impaired handgrip and SPPB. Survival tree leaf node membership had greater predictive accuracy (C-index = 0.81, 95%CI = 0.78–0.84 for the eGFR survival tree and C-index = 0.77, 95%CI = 0.71–0.81 for the ACR survival tree) in comparison with that of individual measures of kidney function. Conclusions physical performance helps to identify a proportion of patients at an increased risk of mortality despite a mild–moderate impairment in kidney function and improves predictive accuracy of individual measures of kidney function. [ABSTRACT FROM AUTHOR]

Background cognitively impaired hospital patients often experience agitation and aggression due to pain. Agitation complicates care, increasing the risk of adverse outcomes and patient-to-nurse violence. Managing agitation is challenging for nurses. Literature suggests they may rely on antipsychotics while missing other more appropriately targeted treatments. However, nurses' management of agitation remains unclear and under-researched. Objective the aim of this study was to investigate hospital nurses' management of agitation in older cognitively impaired patients with pain. Design this was a descriptive correlational study using virtual simulation. Setting and participants a total of 274 registered medical and surgical nurses from 10 public hospitals in Queensland, Australia participated in the study. Methods nurses undertook a virtual simulation requiring them to manage agitation in a patient with dementia and an injury. Nurses also completed a post-simulation questionnaire. Their simulation performances were correlated with demographics such as seniority, workplace, training, experience and gerontology-specific knowledge. Constructed from an original, validated vignette, the simulation included branching pathways, video scenarios and an avatar that could converse with participants. Results thirteen nurses (4.7%) recognised and treated the virtual patient's agitation as pain-related. Most nurses (89%) gave antipsychotics of which 207 (78%) gave these first-line and 102 (38%) used them twice. Independent of other variables, nurses most likely to diagnose pain were dementia-unit nurses (OR = 8.7), surgical-unit nurses (OR = 7.3) and senior nurses (OR = 5). Conclusions hospital nurses predominately managed agitation with antipsychotics, a decision that most made after undertaking inadequate patient assessments. This confirmed a common gap in practice that may lead to the missing of pain in the clinical care of agitated patients with dementia and/or delirium. [ABSTRACT FROM AUTHOR]

Objectives To assess the influence of psoriasis on spinal/pelvic radiographic progression and MRI features in early-stage axial spondyloarthritis (axSpA). Methods Analysis of baseline data from the Italian SPACE cohort, including patients with chronic back pain (CBP; duration ≥3 months and ≤2 years; onset <45 years) was performed. Patients underwent a diagnostic work-up, including MRI and X-rays of the sacroiliac joints (SIJ), to establish diagnosis of axSpA (Assessment of Spondyloarthritis International Society criteria). Clinical features, disease activity and functional indices, imaging were collected at baseline and yearly during 48 months. Spinal and SIJ X-rays and MRIs were scored by two readers following Spondyloarthritis Research Consortium of Canada score, Stoke Ankylosing Spondylitis Spinal Score System modified by Creemers and modified New York criteria. Characteristics of axSpA patients with/without psoriasis were compared over time with descriptive statistics; multivariate logistic regression model was constructed to assess predictors of spinal/pelvic radiographic progression. Results Eighty-eight patients had axSpA (84.1% non-radiographic; 15.9% radiographic); 36.4% had psoriasis. Patients with psoriasis were older; less frequently had HLA-B27+ and radiographic sacroiliitis with unilateral/asymmetric pattern and more signs of spondylitis. Functional and disease activity indices decreased with slightly higher BASDAI and BASFI in axSpA with psoriasis. All patients showed slight spinal/pelvic radiographic progression. Patients without psoriasis showed increased sacroiliitis progression and low-grade spinal progression. More inflammatory corner lesions on cervical/thoracic MRI-spine were observed in patients with psoriasis. A significant downtrend of SPARCC SIJ/spine scores in all patients was found. Psoriasis was a predictor of increased spinal progression (odds ratio = 0.18; 95% CI: 0.04, 0.78). Conclusions Psoriasis was associated with distinct axSpA features, increased spinal radiographic progression and low-grade radiographic sacroiliitis. [ABSTRACT FROM AUTHOR]

Aim This study presents a measure of Social Recovery Capital (SRC) derived from the Important People and Activities instrument (IPA). Methods The sample comprised young adults who participated in the Collaborative Study on the Genetics of Alcoholism, a high-risk family study of alcohol use disorder (N  = 2472). Exploratory and confirmatory factor analysis identified influential items and factor structure, adjusting for family relatedness. The final scale was tested for reliability and validity. Results Factor analysis retained 10 items loading on three factors (Network Abstinence Behaviors, Basic Network Structure and Network Importance) that together explained 42% of the variance in SRC. The total model showed adequate fit (Comparative Fit Index = 0.95; Tucker Lewis Index = 0.93; Root Mean Square Error of Approximation = 0.06; Standardized Root Mean Squared Residual = 0.05) and acceptable reliability (α = 0.60; McDonald's ω  = 0.73) and correlated with validation measures mostly in the weak to moderate range. Due to variable factor scores for reliability and validity, we only recommend using the total score. Conclusion The SRC-IPA is a novel measure of SRC derived from the IPA that captures social network data and has applications in research and clinical work. Secondary data analyses using the SRC-IPA in studies that collected the IPA can further demonstrate the interaction of SRC with a wide variety of clinical indicators and demographic characteristics, making it a valuable addition to other measures of SRC. [ABSTRACT FROM AUTHOR]

Objective To assess the effectiveness of a pharmacist-led intervention using validated tools to reduce medicine-induced deterioration and adverse reactions. Design and setting Multicenter, open-label parallel randomised controlled trial involving 39 Australian aged-care facilities. Participants Residents on ≥4 medicines or ≥1 anticholinergic or sedative medicine. Intervention Pharmacist-led intervention using validated tools to detect signs and symptoms of medicine-induced deterioration which occurred every 8 weeks over 12 months. Comparator Usual care (Residential Medication Management Review) provided by accredited pharmacists. Outcomes Primary outcome was change in Frailty Index at 12 months. Secondary outcomes included changes in cognition, 24-hour movement behaviour by accelerometry, grip strength, weight, adverse events and quality of life. Results 248 persons (median age 87 years) completed the study; 120 in the interventionand, 128 in control arms. In total 575 pharmacist, sessions were undertaken in the intervention arm. There was no statistically significant difference for change in frailty between groups (mean difference: 0.009, 95% CI: −0.028, 0.009, P  = 0.320). A significant difference for cognition was observed, with a mean difference of 1.36 point change at 12 months (95% CI: 0.01, 2.72, P  = 0.048). Changes in 24-hour movement behaviour, grip strength, adverse events and quality of life were not significantly different between groups. Point estimates favoured the intervention arm at 12 months for frailty, 24-hour movement behaviour and grip strength. Conclusions The use of validated tools by pharmacists to detect signs of medicine-induced deterioration is a model of practice that requires further research, with promising results from this trial, particularly with regards to improved cognition. [ABSTRACT FROM AUTHOR]

Population-based seroprevalence surveys can provide useful estimates of the number of individuals previously infected with serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and still susceptible, as well as contribute to better estimates of the case-fatality rate and other measures of coronavirus disease 2019 (COVID-19) severity. No serological test is 100% accurate, however, and the standard correction that epidemiologists use to adjust estimates relies on estimates of the test sensitivity and specificity often based on small validation studies. We have developed a fully Bayesian approach to adjust observed prevalence estimates for sensitivity and specificity. Application to a seroprevalence survey conducted in New York State in 2020 demonstrates that this approach results in more realistic—and narrower—credible intervals than the standard sensitivity analysis using confidence interval endpoints. In addition, the model permits incorporating data on the geographical distribution of reported case counts to create informative priors on the cumulative incidence to produce estimates and credible intervals for smaller geographic areas than often can be precisely estimated with seroprevalence surveys. [ABSTRACT FROM AUTHOR]

Introduction Following the withdrawal of Sabin type 2 from trivalent oral poliovirus vaccine (tOPV) in 2016, the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV) in routine immunization was recommended, either as 1 full dose (0.5mL, intramuscular) or 2 fractional doses of IPV (fIPV—0.1mL, intradermal). India opted for fIPV. We conducted a comparative assessment of IPV and fIPV. Methods This was a 4-arm, open-label, multicenter, randomized controlled trial. Infants were enrolled and vaccines administered according to the study design, and the blood was drawn at age 6, 14, and 18 weeks for neutralization testing against all 3 poliovirus types. Results Study enrolled 799 infants. The seroconversion against type 2 poliovirus with 2 fIPV doses was 85.8% (95% confidence interval [CI]: 80.1%-90.0%) when administered at age 6 and 14 weeks, 77.0% (95% CI: 70.5-82.5) when given at age 10 and 14 weeks, compared to 67.9% (95% CI: 60.4-74.6) following 1 full-dose IPV at age 14 weeks. Conclusion The study demonstrated the superiority of 2 fIPV doses over 1 full-dose IPV in India. Doses of fIPV given at 6 and 14 weeks were more immunogenic than those given at 10 and 14 weeks. Clinical Trial Registry of India (CTRI). Clinical trial registration number was CTRI/2017/02/007793. [ABSTRACT FROM AUTHOR]

Objectives The STRATEGE (Therapeutic Strategy in Patients Treated With Methotrexate for Rheumatoid Arthritis) study aimed to describe treatment strategies in current practice in RA biologic DMARD (bDMARD)-naïve patients with an inadequate response to MTX therapy, and to compare clinical efficacy of the different therapeutic strategies on disease activity after 6 months. Methods The main inclusion criteria of this prospective, observational, multicentre study were confirmed RA diagnosis, treatment by MTX monotherapy and need for therapeutic management modification. Results The 722 patients included had a mean (s. d.) RA duration of 5.3 (6.7) years, a mean DAS28 of 4.0 (1.1); they were all receiving MTX monotherapy, 68% oral, at a mean dose of 15.0 (4.1) mg/week. Two major strategies were identified: (i) MTX monotherapy dose and/or route optimization (72%) and (ii) bDMARD initiation ± MTX (16%). MTX dosing was modified for 70% of patients, maintained (dose and route) for 28% of patients and interrupted for 2%. bDMARDs were started when the MTX mean dose was 17.4 mg/week, 56% parenterally; MTX was maintained concomitantly for 96% of patients. Six-month follow-up results adjusted by propensity score showed that both options were equally successful in improving disease activity and physical function, with 63 and 68% of good-to-moderate EULAR responses, respectively. Conclusion The STRATEGE study shows the importance of initial MTX treatment optimization before initiation of a biological treatment and emphasizes the importance of treat-to-target strategy. Trial registration ClinicalTrials.gov NCT02288520. [ABSTRACT FROM AUTHOR]

Handwriting kinematics (HWKs) were assessed in the randomized controlled ALPINE study of 2 long-acting injectable antipsychotics started during an acute exacerbation of schizophrenia. This exploratory analysis examined the relationship between baseline HWKs and response to acute antipsychotic treatment. Adults with acute schizophrenia were assigned to aripiprazole lauroxil or paliperidone palmitate (groups combined for this analysis). Treatment response was defined as ≥20% reduction from baseline in Positive and Negative Syndrome Scale (PANSS) total score at week 4. Two HWK measures, peak velocity (decreases with greater dysfunction) and percentage of nonballistic movements (%NBM; increases with greater dysfunction), were captured in 4 handwriting tasks (complex loops, maximum speed circles, overlay circles, and left-right loops). Peak velocity and %NBM at baseline were compared between responders and nonresponders. The analysis included 143 patients (mean baseline PANSS total score, 94.5). PANSS responders (n = 67 [46.9%]) had a lower mean peak velocity (i.e. slower pen movements) on all HWK tasks at baseline compared with nonresponders (n = 76): complex loops, 8.8 versus 12.1 cm/s; maximum speed circles, 18.0 versus 23.7 cm/s; overlay circles, 12.6 versus 17.2 cm/s; and left-right loops, 11.2 versus 14.6 cm/s. PANSS responders had a greater %NBM on 3 tasks compared with nonresponders: complex loops, 57.1% versus 47.4%; overlay circles, 30.6% versus 24.3%; and left-right loops, 58.7% versus 47.0%. In this exploratory analysis, PANSS responders to aripiprazole lauroxil or paliperidone palmitate treatment at week 4 had lower baseline HWK movement velocities and greater baseline %NBM versus nonresponders, suggesting that baseline HWKs might predict response to these antipsychotic drugs. [ABSTRACT FROM AUTHOR]

Background This study aimed to compare knowledge, attitude and practice (KAP) regarding COVID-19 between public health workers (PHWs) attended field epidemiology training program (FETP-trained) and those who did not attend FETP (non-FETP trained). Methods Multi-country cross-sectional survey was conducted among PHWs who participated in COVID-19 pandemic in 10 countries at EMR. Online questionnaire that included demographic information, KAP regarding COVID-19 pandemic was distributed among HCWs. Scoring system was used to quantify the answers, bivariate and Multivariate analysis performed to compare FETP-trained with non-FETP trained PHWs. Results Overall, 1337 PHWs participated, with 835 (62.4%) < 40 years of age, and 851 (63.6%) males. Of them, 423 (31.6%) had FETP, including that 189 (44.7%) had advanced level, 155 (36.6%) intermediate and 79 (18.7%) basic level training. Compared with non-FETP trained, FETP trained were older, having higher KAP scores. FETP participation was low in infection control, and PH laboratories. KAP mean scores for intermediate level attendees are comparable to advanced level. Conclusions FETP-trained are having better KAP than non-FETP PHWs. Expanding the intermediate level, maintain the Rapid Response training and introduce the laboratory component are recommended to maximize the benefit from FETP. Infection control, antimicrobial resistance and coordination are areas where training should include. [ABSTRACT FROM AUTHOR]

Background Despite efforts to increase coverage by two doses of measles vaccine in Italy, measles continues to circulate, with over 13 000 cases of disease since 2013. This study aimed to evaluate immunity to measles in Italian children and adolescents. Methods A total of 378 serum samples from subjects aged 9 months–18 years were collected in Northern, Central and Southern regions of Italy between 2012 and 2016. Specific IgG antibodies against measles were measured by a commercial ELISA kit. Results The frequency of IgG-positive samples ranged from 10.5% in infants under 1 year to 98.3% in children aged 6–7 years. The frequency of IgG was 72.2% in subjects aged 1–2 years, 85.6% in those aged 3–5 years and 88.3 and 86.8% in those aged 8–10 and 11–18 years, respectively. In Northern Italy, IgG prevalence was consistent with data on vaccination coverage, whereas some differences were observed in samples from subjects aged more than 8 years in Central and Southern Italy. Conclusions Our findings confirm that a large proportion of children and adolescents in Italy are still susceptible to measles. While data on first- and second-dose measles vaccination are essential, they are not sufficient to identify susceptible population cohorts to be targeted by vaccination. [ABSTRACT FROM AUTHOR]

Objective To investigate the long-term outcomes of patients with RA after myocardial infarction (MI). Methods All-comer, real-life MI patients with RA (n  = 1614, mean age 74 years) were retrospectively compared with propensity score (1:5) matched MI patients without RA (n  = 8070) in a multicentre, nationwide, cohort register study in Finland. The impact of RA duration and the usage of corticosteroids and antirheumatic drugs on RA patients' outcomes were also studied. The median follow-up was 7.3 years. Results RA was associated with an increased 14-year mortality risk after MI compared with patients without RA [80.4% vs 72.3%; hazard ratio (HR) 1.25; CI: 1.16, 1.35; P  <0.0001]. Patients with RA were at higher risk of new MI (HR 1.22; CI: 1.09, 1.36; P  =0.0001) and revascularization (HR 1.28; CI: 1.10, 1.49; P  =0.002) after discharge from index MI. Cumulative stroke rate after MI did not differ between RA and non-RA patients (P  =0.322). RA duration and corticosteroid usage before MI, but not use of methotrexate or biologic antirheumatic drugs, were independently associated with higher mortality (P  <0.001) and new MI (P  =0.009). A higher dosage of corticosteroids prior to MI was independently associated with higher long-term mortality (P  =0.002) and methotrexate usage with lower stroke rate (P  =0.034). Serological status of RA was not associated with outcomes. Conclusion RA is independently associated with poorer prognosis after MI. RA duration and corticosteroid usage and dosage were independent predictors of mortality after MI in RA. Special attention is needed for improvement of outcomes after MI in this vulnerable population. [ABSTRACT FROM AUTHOR]

Aim Investigate changes in alcohol use and related harm using the first multisite, controlled, longitudinal study of Managed Alcohol Programs (MAPs). MAPs provide regular doses of alcohol, accommodation, social supports and healthcare to unstably housed people with alcohol dependence. Methods A multisite, quasi-experimental, longitudinal study was conducted in day centres, shelters and residential programs for unstably housed people. There were 59 MAP participants from six Canadian cities and 116 local controls. Self-reported alcohol consumption and harms were assessed at 0-2, 6 and 12 months. Liver function test results were accessed for MAP participants. Results Both groups had similar reductions in mean drinks per day (MAP: -8.11; controls: -8.54 controls, P < 0.001) and days drinking per month (MAP: -2.51 days, P < 0.05; control: -4.81 days, P = 0.0001) over 6–-12 months. Both reduced non-beverage alcohol consumption. MAP participants reported significantly fewer harms at both 0-2 and 6 months than controls. MAP participants had similar total consumption to controls, but spread out over more days (25.41 versus 19.64 days per month, P = 0.001). After leaving a MAP, participants' liver status deteriorated, with increases in both aspartate transaminase and bilirubin levels. MAP sites with effective policies on outside drinking drank less and had fewer harms. Conclusion MAP participants drank less hazardously than controls, especially with effective management of non-MAP drinking. Reductions in alcohol use and harms occurred for both groups, although MAP participants reported fewer harms at 0-6 months. Departing an MAP was associated with deterioration in liver status. Although providing stable housing, MAPs did not worsen health or increase alcohol use. [ABSTRACT FROM AUTHOR]

Background: Grade 3 gastroenteropancreatic neuroendocrine neoplasms (G3 GEPNENs) are often aggressive, and the optimal treatment is unclear for this subgroup of neuroendocrine neoplasms (NENs). Temozolomide (TEM)‐based regimens have been increasingly used to treat grade 1–2 NENs, but their efficacy in G3 NENs remains undetermined. We aimed to assess the clinical efficacy of TEM‐containing regimens in advanced grade 3 GEPNENs. Materials and Methods: A multicenter retrospective review (2008–2018) of patients with metastatic/unresectable G3 GEPNENs who received a TEM‐containing regimen was undertaken within a North American partnership to pool data. The primary endpoint was time to treatment failure (TTF). Radiologic response was extracted from local reports. Results: One hundred and thirty patients in six high‐volume NEN centers were included (median age 55, 64% male, 18% functional, 67% pancreatic NEN). Forty‐nine percent were well‐differentiated, 35% poorly differentiated, and 15% unknown based on local pathology reports. The regimen used was capecitabine and temozolomide (CAPTEM) in 92% and TEM alone in 8%. Radiological response by local assessment was seen in 36% of patients. Median TTF was 3.6 months and median overall survival (OS) 19.2 months. Six percent of patients required discontinuation of therapy due to adverse events. TTF was longer in first‐line treatment (7.8 months vs. 2.9 months; hazard ratio, 1.62; 95% confidence interval, 1.11–2.36; p =.015) and in patients with pancreatic NENs (panNENs) compared with gastrointestinal NENs (5.8 months vs 1.8 months; p =.04). The overall response rate was higher in the first‐line setting (51% vs 29%; p =.02) and in panNEN (41% vs 23%; p =.04). Conclusion: This is the largest TEM treatment series in G3 NEN, involving collaboration of several major North American NEN centers as a partnership. Thirty‐six percent of patients showed some degree of radiographic response, and treatment was generally well tolerated, although the median duration of response was short. Response rates and time to treatment failure were superior in the first‐line setting. CAPTEM should be considered a viable treatment option in this setting. Further randomized trials are warranted. Implications for Practice: Neuroendocrine neoplasms (NENs) are heterogeneous, and optimal treatment for aggressive grade 3 (G3) NENs remains undetermined. The capecitabine and temozolomide (CAPTEM) regimen has been used in low‐grade pancreas NENs but there are few data for its safety and efficacy in the G3 setting. This article reports on the efficacy of temozolomide‐containing regimens, particularly CAPTEM, in management of G3 NENs. The good tolerance and response rate show that CAPTEM should be considered a viable regimen in treatment of G3 NENs pending confirmatory prospective studies. There has been increasing interest in the combination of capecitabine and temozolomide (CAPTEM) for the treatment of gastroenteropancreatic neuroendocrine neoplasm (GEPNEN). This review reports a large retrospective analysis to report the efficacy and tolerability of temozolomide (TEM)‐containing regimens, particularly CAPTEM, in patients with grade 3 GEPNENs. [ABSTRACT FROM AUTHOR]

Objective To investigate the occurrence of venous thromboembolic events (VTE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, Turkey, Russia, UK and North America. Methods Patients with a definite diagnosis of AAV who were followed for at least 3 months and had sufficient documentation were included. Data on VTE, including either deep vein thrombosis or pulmonary embolism, were collected retrospectively from tertiary vasculitis centres. Univariate and multivariate regression models were used to estimate odds ratios (ORs) and 95% CIs. Results Over a median follow-up of 63 (interquartile range: 29, 101) months, VTE occurred in 278 (9.7%) of 2869 AAV patients with a similar frequency across different countries (from 6.3% to 13.7%), and AAV subtype [granulomatosis with polyangiitis: 9.8% (95% CI: 8.3, 11.6%); microscopic polyangiitis: 9.6% (95% CI: 7.9, 11.4%); and eosinophilic granulomatosis with polyangiitis: 9.8% (95% CI: 7.0, 13.3%)]. Most VTE (65.6%) were reported in the first-year post-diagnosis. Multiple factor logistic regression analysis adjusted for sex and age showed that skin (OR 1.71, 95% CI: 1.01, 2.92), pulmonary (OR 1.78, 95% CI: 1.04, 3.14) and kidney [eGFR 15–60 ml/min/1.73 m2, OR 2.86 (95% CI: 1.27, 6.47); eGFR <15 ml/min/1.73 m2, OR 6.71 (95% CI: 2.94, 15.33)] involvement were independent variables associated with a higher occurrence of VTE. Conclusion Two-thirds of VTE occurred during the initial phase of active disease. We confirmed previous findings from smaller studies that a decrease in kidney function, skin involvement and pulmonary disease are independently associated with VTE. [ABSTRACT FROM AUTHOR]

Background This study explored barriers and facilitators to integrating health evidence into spatial planning at local authority levels and examined the awareness and use of the Public Health England 'Spatial Planning for Health' resource. Methods A sequential exploratory mixed-methods design utilized in-depth semi-structured interviews followed by an online survey of public health, planning and other built environment professionals in England. Results Views from 19 individuals and 162 survey responses revealed high awareness and use of the Spatial Planning for Health resource, although public health professionals reported greater awareness and use than other professionals. Key barriers to evidence implementation included differences in interpretation and the use of 'evidence' between public health and planning professionals, lack of practical evidence to apply locally and lack of resource and staff capacity in local authorities. Key facilitators included integrating health into the design of local plans, articulating wider benefits to multiple stakeholders and simplifying presenting evidence (regarding language and accessibility). Conclusion The Spatial Planning for Health resource is a useful resource at local authority level. Further work is needed to maximize its use by built environment professionals. Public health teams need support, capacity and skills to ensure that local health and well-being priorities are integrated into local planning documents and decisions. [ABSTRACT FROM AUTHOR]

Background Sepsis is one of the most frequent reasons for acute intensive care unit (ICU) admission of very old patients and mortality rates are high. However, the impact of pre-existing physical and cognitive function on long-term outcome of ICU patients ≥ 80 years old (very old intensive care patients (VIPs)) with sepsis is unclear. Objective To investigate both the short- and long-term mortality of VIPs admitted with sepsis and assess the relation of mortality with pre-existing physical and cognitive function. Design Prospective cohort study. Setting 241 ICUs from 22 European countries in a six-month period between May 2018 and May 2019. Subjects Acutely admitted ICU patients aged ≥80 years with sequential organ failure assessment (SOFA) score ≥ 2. Methods Sepsis was defined according to the sepsis 3.0 criteria. Patients with sepsis as an admission diagnosis were compared with other acutely admitted patients. In addition to patients' characteristics, disease severity, information about comorbidity and polypharmacy and pre-existing physical and cognitive function were collected. Results Out of 3,596 acutely admitted VIPs with SOFA score ≥ 2, a group of 532 patients with sepsis were compared to other admissions. Predictors for 6-month mortality were age (per 5 years): Hazard ratio (HR, 1.16 (95% confidence interval (CI), 1.09–1.25, P  < 0.0001), SOFA (per one-point): HR, 1.16 (95% CI, 1.14–1.17, P  < 0.0001) and frailty (CFS > 4): HR, 1.34 (95% CI, 1.18–1.51, P  < 0.0001). Conclusions There is substantial long-term mortality in VIPs admitted with sepsis. Frailty, age and disease severity were identified as predictors of long-term mortality in VIPs admitted with sepsis. [ABSTRACT FROM AUTHOR]

Aims Two complementary studies were used to assess the real-life use of nalmefene in alcohol-dependent patients and its impact on alcohol use health status. Methods USE-PACT was a prospective cohort study designed to evaluate the real-life effectiveness of nalmefene in the management of alcohol dependence, as assessed by total alcohol consumption (TAC) and number of heavy drinking days (HDD) at 1 year. USE-AM was a cohort study using data from the French nationwide claims database and was used to evaluate the external validity of the population in the prospective study. Results Overall, 256 of 700 new nalmefene users enrolled in the USE-PACT study had valid data at 1 year. After 1 year, patients treated with nalmefene showed a mean ± SD reduction from baseline in TAC (−41.5 ± 57.4 g/day) and number of HDD (−10.7 ± 11.7 days/4 weeks). Patients took a mean ± SD of 20.0 ± 12.0 tablets/4 weeks (median of 1 tablet/day) for the first 3 months and then reduced the dose. The proportion of patients who no longer took nalmefene gradually increased from 5% at 1 month to 52% at 1 year. The USE-AM study identified 486 patients with a first reimbursement for nalmefene in 2016; baseline characteristics confirmed external validity of the USE-PACT study. Overall, 46.3% of initial USE-AM prescriptions were made by GPs; most (91.8%) patients stopped treatment during follow-up. However, 15.2% of patients resumed treatment after stopping. Conclusions In this analysis of French routine practice, patients with alcohol dependence treated with nalmefene showed reduced alcohol consumption, and nalmefene was generally well tolerated. [ABSTRACT FROM AUTHOR]