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Background Evidence about the clinical impact of rapid diagnostic tests (RDTs) for the diagnosis of bloodstream infections is limited, and whether RDT are superior to conventional blood cultures (B Cs) embedded within antimicrobial stewardship programs (ASPs) is unknown. Methods We performed network meta-analyses using results from studies of patients with bloodstream infection with the aim of comparing the clinical impact of RDT (applied on positive BC broth or whole blood) to conventional BC, both assessed with and without ASP with respect to mortality, length of stay (LOS), and time to optimal therapy. Results Eighty-eight papers were selected, including 25 682 patient encounters. There was an appreciable amount of statistical heterogeneity within each meta-analysis. The network meta-analyses showed a significant reduction in mortality associated with the use of RDT + ASP versus BC alone (odds ratio [OR], 0.72; 95% confidence interval [CI],.59–.87) and with the use of RDT + ASP versus BC + ASP (OR, 0.78; 95% CI,.63–.96). No benefit in survival was found associated with the use of RDT alone nor with BC + ASP compared to BC alone. A reduction in LOS was associated with RDT + ASP versus BC alone (OR, 0.91; 95% CI,.84–.98) whereas no difference in LOS was shown between any other groups. A reduced time to optimal therapy was shown when RDT + ASP was compared to BC alone (−29 hours; 95% CI, −35 to −23), BC + ASP (−18 hours; 95% CI, −27 to −10), and to RDT alone (−12 hours; 95% CI, −20 to −3). Conclusions The use of RDT + ASP may lead to a survival benefit even when introduced in settings already adopting effective ASP in association with conventional BC. [ABSTRACT FROM AUTHOR]

Family group conferences (FGCs) in child welfare share decision-making with family members by bringing the immediate and wider family together to make a plan to meet a child's needs. This paper reports survey findings on FGC provision in the UK in 2022 and explores whether in England the presence of an FGC service and the rate of FGC provision is associated with the rate of children in care, entering care, in kinship foster care and leaving care. Seventy-nine per cent (n  = 167) of local authorities in the UK provided FGCs to families, and 14 per cent (n  = 29) did not. Services that were more established offered a more diverse range of FGCs. The introduction of FGCs in English local authorities was associated with a higher rate of children in care, but also higher rates of kinship foster care, a key goal of FGCs where it is not possible for children to stay with their parents. Higher rates of FGCs were associated with more children leaving care, possibly due to reunification with birth families. To understand in more detail, the circumstances of children in and leaving care in local authorities with FGCs, individual data linkage studies are needed. [ABSTRACT FROM AUTHOR]

In this paper, we present a practical approach for computing the sandwich variance estimator in 2-stage regression model settings. As a motivating example for 2-stage regression, we consider regression calibration, a popular approach for addressing covariate measurement error. The sandwich variance approach has rarely been applied in regression calibration, despite its requiring less computation time than popular resampling approaches for variance estimation, specifically the bootstrap. This is probably because it requires specialized statistical coding. Here we first outline the steps needed to compute the sandwich variance estimator. We then develop a convenient method of computation in R for sandwich variance estimation, which leverages standard regression model outputs and existing R functions and can be applied in the case of a simple random sample or complex survey design. We use a simulation study to compare the sandwich estimator to a resampling variance approach for both settings. Finally, we further compare these 2 variance estimation approaches in data examples from the Women's Health Initiative (1993–2005) and the Hispanic Community Health Study/Study of Latinos (2008–2011). In our simulations, the sandwich variance estimator typically had good numerical performance, but simple Wald bootstrap confidence intervals were unstable or overcovered in certain settings, particularly when there was high correlation between covariates or large measurement error. [ABSTRACT FROM AUTHOR]

This systematic review evaluated the impact of oral probiotics on the immune response to vaccination in older people. A literature search was performed in three electronic databases up to January 2023. Randomised controlled trials (RCTs) conducted in older people (age ≥ 60 years) investigating oral probiotics and vaccine response outcomes were included. Characteristics and outcome data of the included studies were extracted and analysed and study quality was assessed using the Cochrane Risk of Bias Tool for randomised trials. Ten RCTs involving 1,560 participants, reported in 9 papers, were included. Nine studies involved the seasonal influenza vaccine and one a COVID-19 vaccine. All studies used lactobacilli, some in combination with bifidobacteria. Studies reported outcomes including anti-vaccine antibody titres or concentrations, seroconversion and seroprotection. When comparing antibody titres, seroprotection rate and seroconversion rate between probiotic and placebo groups expressed as a response ratio, the weighted mean values were 1.29, 1.16 and 2.00, respectively. Meta-analysis showed that probiotics increase seroconversion rates to all three strains of the seasonal influenza vaccine: odds ratio (95% confidence interval) 2.74 (1.31, 5.70; P  = 0.007) for the H1N1 strain; 1.90 (1.04, 3.44; P  = 0.04) for the H3N2 strain; 1.72 (1.05, 2.80; P  = 0.03) for the B strain. There was a low level of heterogeneity in these findings. Several studies were at high risk of bias due to missing outcome data. Lactobacilli may improve the vaccine response, but further research is needed to be more certain of this. [ABSTRACT FROM AUTHOR]

In this paper, we advocate and expand upon a previously described monitoring strategy for efficient and robust estimation of disease prevalence and case numbers within closed and enumerated populations such as schools, workplaces, or retirement communities. The proposed design relies largely on voluntary testing, which is notoriously biased (e.g. in the case of coronavirus disease 2019) due to nonrepresentative sampling. The approach yields unbiased and comparatively precise estimates with no assumptions about factors underlying selection of individuals for voluntary testing, building on the strength of what can be a small random sampling component. This component enables the use of a recently proposed "anchor stream" estimator, a well-calibrated alternative to classical capture-recapture (CRC) estimators based on 2 data streams. We show that this estimator is equivalent to a direct standardization based on "capture," that is, selection (or not) by the voluntary testing program, made possible by means of a key parameter identified by design. This equivalency simultaneously allows for novel 2-stream CRC-like estimation of general mean values (e.g. means of continuous variables like antibody levels or biomarkers). For inference, we propose adaptations of Bayesian credible intervals when estimating case counts and bootstrapping when estimating means of continuous variables. We use simulations to demonstrate significant precision benefits relative to random sampling alone. [ABSTRACT FROM AUTHOR]

Aims: This paper aims to assess kinematic parameters related to functional capacity, fatigue, and breathlessness during the 6-min walk test (6MWT) in patients with heart failure with preserved ejection fraction (HFpEF). Methods and results: A cross-sectional study was conducted in which adults 70 years or older with HFpEF were voluntarily recruited between April 2019 and March 2020. An inertial sensor was placed at the L3–L4 level and another on the sternum to assess kinematic parameters. The 6MWT was divided into two 3-min phases. Leg fatigue and breathlessness, assessed by the Borg scale, the heart rate (HR), and the oxygen saturation (SpO2), were measured at the beginning and the end of the 6MWT. The difference in kinematic parameters between the 6MWT two 3-min phases was also calculated. Bivariate Pearson correlations and subsequent multivariate linear regression analysis were performed. Seventy older adults with HFpEF (mean = 80.74 years old) were included. Kinematic parameters explained 81.00% of the functional capacity, 45.50% of the leg fatigue and 66.10% of the breathlessness variance. Moreover, kinematic parameters could explain 30.90% of the SpO2 variance at the end of the 6MWT. Kinematic parameters also explained 33.10% of the SpO2 difference between the beginning and end of 6MWT. Kinematic parameters explained neither the HR variance at the end of 6MWT nor the HR difference between the beginning and end. Conclusion: Gait kinematics from L3-L4 and sternum explain a part of the variance in subjective outcomes, assessed by the Borg scale, and objective outcomes such as functional capacity and SpO2. The kinematic assessment allows clinicians to quantify fatigue and breathlessness through objective parameters related to the patient's functional capacity. Registration: ClinicalTrials.gov NCT03909919. Graphical Abstract [ABSTRACT FROM AUTHOR]

Introduction Standard investigator-based adverse events (AE) assessment is via CTCAE for clinical trials. However, including the patient perspective through PRO (patient-reported outcomes) enhances clinicians' understanding of patient toxicity and fosters early detection of AEs. We assessed longitudinal integration of PRO-CTCAE within clinical workflow in a phase II trial. Materials and methods As a sub-study in a phase II trial of genotype-directed irinotecan dosing evaluating efficacy in patients with metastatic colorectal cancer receiving FOLFIRI and bevacizumab, patients reported on 13 AEs generating a PRO-CTCAE form. The primary objective was to estimate forms completed by patients and clinicians at least 80% of time. Secondary objectives were estimating concordance and time to first score of specific symptoms between patient and clinician pairs. Results Feasibility of longitudinal PRO-CTCAE integration was met as 96% of patients and clinician-patient pairs completed at least 80% of PRO-CTCAE forms available to them with 79% achieving 100% completion. Concordance between patient and clinician reporting a severe symptom was 73% with 24 disconcordant pairs, 21 involved patients who reported a severe symptom that the clinician did not. Although protocol-mandated dose reductions were guided by CTCAE not PRO-CTCAE responses, the median time to dose reduction of 2.53 months, and the time-to-event curve closely approximated time to patient-reported toxicity. Conclusion Longitudinal integration of PRO-CTCAE paired CTCAE proved feasible. Compared to clinicians, patients reported severe symptoms more frequently and earlier. Patient-reported toxicity more closely aligned with dose decreases indicating incorporation into routine clinical practice may enhance early detection of toxicity improving patient safety and quality of life. [ABSTRACT FROM AUTHOR]

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 Social inequalities in multimorbidity may occur due to familial and/or individual factors and may differ between men and women. Using population-based multi-generational data, this study aimed to (1) assess the roles of parental and individual education in the risk of multimorbidity and (2) examine the potential effect modification by sex. Methods Data were analysed from 62 060 adults aged 50+ who participated in the Survey of Health, Ageing and Retirement in Europe, comprising 14 European countries. Intergenerational educational trajectories (exposure) were High–High (reference), Low–High, High–Low and Low–Low, corresponding to parental–individual educational attainments. Multimorbidity (outcome) was ascertained between 2013 and 2020 as self-reported occurrence of ≥2 diagnosed chronic conditions. Inequalities were quantified as multimorbidity-free years lost (MFYL) between the ages of 50 and 90 and estimated via differences in the area under the standardized cumulative risk curves. Effect modification by sex was assessed via stratification. Results Low individual education was associated with higher multimorbidity risk regardless of parental education. Compared to the High–High trajectory, Low–High was associated with −0.2 MFYL (95% confidence intervals: −0.5 to 0.1), High–Low with 3.0 (2.4–3.5), and Low–Low with 2.6 (2.3–2.9) MFYL. This pattern was observed for both sexes, with a greater magnitude for women. This effect modification was not observed when only diseases diagnosed independently of healthcare-seeking behaviours were examined. Conclusions Individual education was the main contributor to intergenerational inequalities in multimorbidity risk among older European adults. These findings support the importance of achieving a high education to mitigate multimorbidity risk. [ABSTRACT FROM AUTHOR]

Background The American Heart Association recently released an updated algorithm for evaluating cardiovascular health—Life's Essential 8 (LE8). However, the associations between changes in LE8 score over time and risk of cardiovascular disease (CVD) remain unclear. Methods We investigated associations between 6-year changes (2006–12) in LE8 score and risk of subsequent CVD events (2012–20) among 53 363 Chinese men and women from the Kailuan Study, who were free from CVD in 2012. The LE8 score was calculated based on eight components: diet quality, physical activity, smoking status, sleep health, body mass index, blood lipids, blood glucose and blood pressure. Multivariable-adjusted Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results We documented 4281 incident CVD cases during a median of 7.7 years of follow-up. Compared with participants whose LE8 scores remained stable in a 6-year period, those with the large increases of LE8 score over the 6-year period had a lower risk of CVD, heart disease and stroke in the subsequent 8 years [HRs and 95% CIs: 0.67 (0.64, 0.70) for CVD, 0.65 (0.61, 0.69) for heart disease, 0.71 (0.67, 0.76) for stroke, all P trend < 0.001]. Conversely, those with the large decreases of LE8 score had 47%, 51% and 41% higher risk for CVD, heart disease and stroke, respectively. These associations were consistent across the subgroups stratified by risk factors. Conclusions Improving LE8 score in a short- and moderate-term was associated with a lower CVD risk, whereas decreased LE8 score over time was associated with a higher risk. [ABSTRACT FROM AUTHOR]

Objective Physical activity is recommended for recipients of a kidney transplant. However, ADHERE BRAZIL study found a high prevalence (69%) of physical inactivity in Brazilian recipients of a kidney transplant. To tackle this behavior, a broad analysis of barriers is needed. This study aimed to identify factors (patient and transplant center levels) associated with physical inactivity among recipients of a kidney transplant. Methods This was a subproject of the ADHERE BRAZIL study, a cross-sectional, multicenter study of 1105 recipients of a kidney transplant from 20 kidney transplant centers. Using a multistage sampling method, patients were proportionally and randomly selected. Applying the Brief Physical Activity Assessment questionnaire, patients were classified as physically active (≥150 min/wk) or physically inactive (<150 min/wk). On the basis of an ecological model, 34 factors associated with physical inactivity were analyzed by sequential logistic regression. Results At the patient level, physical inactivity was associated with smoking (odds ratio = 2.43; 95% CI = 0.97–6.06), obesity (odds ratio = 1.79; 95% CI = 1.26–2.55), peripheral vascular disease (odds ratio = 3.18; 95% CI = 1.20–8.42), >3 posttransplant hospitalizations (odds ratio = 1.58; 95% CI = 1.17–2.13), family income of >1 reference salary ($248.28 per month; odds ratio = 0.66; 95% CI = 0.48–0.90), and student status (odds ratio = 0.58; 95% CI = 0.37–0.92). At the center level, the correlates were having exercise physiologists in the clinical team (odds ratio = 0.54; 95% CI = 0.46–0.64) and being monitored in a teaching hospital (undergraduate students) (odds ratio = 1.47; 95% CI = 1.01–2.13). Conclusions This study identified factors associated with physical inactivity after kidney transplantation that may guide future multilevel behavioral change interventions for physical activity. Impact In a multicenter sample of recipients of a kidney transplant with a prevalence of physical inactivity of 69%, we found associations between this behavior and patient- and center-level factors. At the patient level, the chance of physical inactivity was positively associated with smoking, obesity, and patient morbidity (peripheral vascular disease and hospitalization events after kidney transplantation). Conversely, a high family income and a student status negatively correlated with physical inactivity. At the center level, the presence of a dedicated professional to motivate physical activity resulted in a reduced chance of physical inactivity. A broad knowledge of barriers associated with physical inactivity can allow us to identify patients at a high risk of not adhering to the recommended levels of physical activity. [ABSTRACT FROM AUTHOR]

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

Background 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]

Objective. Specific neck exercises are recommended in the rehabilitation of chronic nonspecific neck pain (CNNP). They are unfortunately often accompanied by acute pain flare-ups. Global exercises might be a beneficial addition, as they activate endogenous analgesia without overloading painful structures. However, it is still unclear which type of exercise is most effective. This randomized controlled trial was done to evaluate the effect of an online blended program of global and specific neck exercises, compared to programs including only 1 of both types of exercise. Methods. Forty-eight patients with CNNP were randomized into 3 groups. Online questionnaires were collected at baseline, at midtreatment, immediately after treatment, and at the 3-month follow-up. Quantitative sensory testing and actigraphy were assessed at baseline and after treatment. Linear mixed-model analyses were performed to evaluate treatment effects within and between groups. Neck pain-related disability after treatment was considered the primary outcome. Results. No time x treatment interaction effects were found. All groups improved in neck pain-related disability, pain intensity, self-reported symptoms of central sensitization, local pain sensitivity, physical activity, and pain medication use. No effects were found on quality of life, sleep quality, depression, anxiety, stress, widespread pain sensitivity, health economics, or actigraphy measurements. A higher global perceived effect was reported after performing the blended program, compared to the other groups. Conclusion. A blended exercise program was not superior to the stand-alone programs in reducing disability. Nevertheless, the global perceived effect of this type of exercise was higher. Future research necessitates larger sample sizes to adequately explore the optimal type of exercise for patients with CNNP. Impact. Exercise therapy should be an important part of the rehabilitation of patients with CNNP, regardless of the type of exercise. [ABSTRACT FROM AUTHOR]

Background Young adults in Neither in Employment, Education nor Training (NEET) are at risk of adverse labour market outcomes. Earlier studies often measured NEET status at one time point or compared persistent NEETs with non-NEETs, neglecting other patterns of NEET status. Evidence on early life factors associated with NEET patterns is lacking. This study aims to (i) identify patterns of NEET status over time and (ii) examine whether factors in childhood and adolescence are associated with these patterns. Methods Data were used from 1499 participants of the TRacking Adolescents' Individual Lives Survey (TRAILS), a Dutch prospective cohort study with 15-year follow-up. NEET status was assessed at ages 19, 22 and 26. Socioeconomic status of parents (SES), intelligence and negative life events were measured at age 11, educational attainment at age 26 and mental health problems at ages 11, 13.5 and 16. Data were analyzed using multinomial logistic regression analysis. Results Four NEET patterns were identified: (i) non-NEETs (85.2%), (ii) early NEETs (4.5%), (iii) late NEETs (5.7%) and (iv) persistent NEETs (4.5%). Reporting internalizing problems at age 11 was a risk factor for early and late NEETs [odds ratio (OR) 2.77, 95% confidence interval (CI) 1.16–6.62; OR 5.00, 95% CI 2.22–11.3, respectively]. Low parental SES, lower intelligence scores and negative life events (≥3) were risk factors for persistent NEETs (OR 4.45, 95% CI 2.00–9.91; OR 0.96, 95% CI 0.94–0.98; OR 4.42, 95% CI 1.62–12.08, respectively). Conclusions The results highlight the importance of timing and duration of NEET status and emphasize the need for tailored interventions to prevent specific NEET patterns. [ABSTRACT FROM AUTHOR]

Background Socioeconomic inequalities constitute an important focus area for public health, and it has long been established that higher educational level and longer lifespan are correlated. Little is known about decennial time trends in poor self-rated health and mental distress. Methods This study linked decennial cross-sectional survey data on self-rated health and mental distress from the Trøndelag Health Study (HUNT) from 1984 to 2019 with educational registry data using personal identification numbers. Survey participation ranged from 50 807 to 77 212. Slope index of inequality (SII) and relative index of inequality (RII) were calculated using generalized linear models in Stata. Analyses were stratified by sex and age, using the age categories of 30–59 years and 60–80 years. Results Absolute inequalities in self-rated health and mental distress between educational groups have stayed relatively stable throughout all rounds of HUNT. Relative inequalities in self-rated health and mental distress have generally increased, and both men and women with the lowest education level were more likely to experience poor self-rated health and mental distress relative to those with the highest education level. RII in self-rated health increased over time for both sexes and both age groups. RII for mental distress increased in both sexes and both age groups, except for men and women aged 60–80. Discussion This study shows that relative inequalities in self-rated and mental health in the Norwegian population are still persistent and have increased. Further knowledge about groups with a disadvantageous health situation should have implications for health care resource allocation. [ABSTRACT FROM AUTHOR]

Background During the Coronavirus Disease 2019 (COVID-19) pandemic, immunization programmes struggled to reach all population groups equally. While migrant groups face multiple barriers to health systems, including vaccination, little is known about their vaccine uptake. Methods We conducted a cross-sectional telephone survey on adults with and without migration history in Germany to investigate barriers and drivers to COVID-19 vaccination (11 April 2021 to 18 December 2021). Interviews were conducted in six languages. We used logistic regression models and a mediation model to analyze the association between migration history and vaccine uptake. Furthermore, we determined the effect of psychological determinants (5C model) on vaccine uptake. Results The survey comprised 2039 individuals, including 1015 with migration history. Of these, 448 were interviews conducted in languages other than German. Individuals with migration history had a significantly lower vaccine uptake but, while still unvaccinated, had a higher intention to get vaccinated (P  = 0.015) compared with those without migration history. The association between migration history and vaccine uptake was no longer significant when other factors were included in the regression model (odds ratio = 0.9; 95% confidence interval: 0.57–1.47). Socio-economic index, language skills and discrimination experience fully mediated this association. Among the psychological determinants, 'higher confidence' and 'higher collective responsibility' increased the chance of individuals with migration history to be vaccinated. Conclusion Migration history alone cannot explain vaccine uptake; socio-economic index, language skills and discrimination experiences need to be considered. To achieve vaccine equity, future public health policy should aim to reduce relevant barriers through tailored interventions. [ABSTRACT FROM AUTHOR]

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

Background: Coronavirus disease 2019 (COVID-19) caused major disruptions in healthcare services worldwide. Yet, little is known about the association between perceived disruption in healthcare services and sociodemographic factors, pre-existing health conditions as well as concurrent physical and psychological symptoms. Methods: Leveraging data from the Icelandic COVID-19 National Resilience Cohort, we performed a repeated measure analysis among 15 754 participants who responded to the question on perceived disruption in healthcare services from December 2020 to July 2021, to explore its association with socio-demographic factors, health indicators and conditions. Furthermore, we performed a longitudinal analysis among 7848 participants with two repeated measures to explore the association between timing and duration of perceived disruption in healthcare services and changes in depression, anxiety, sleep quality and somatic symptoms. Results: The prevalence of perceived disruption in healthcare services slightly decreased over time (P<0.01). Perceived disruption in healthcare services was more prevalent among individuals with pre-existing health conditions, i.e. history of psychiatric disorders (prevalence ratio=1.59, 95% confidence interval 1.48-1.72) and chronic somatic conditions [1.40 (1.30-1.52)]. However, no increase in the prevalence of perceived disruption in healthcare services was observed among individuals diagnosed with COVID-19 [0.99 (0.84-1.18)]. Moreover, we found that emerging perceived disruption in healthcare services was associated with an increase in symptoms of mental illness during the pandemic (bs 0.06-0.68). Conclusions: A disruption in healthcare services during the COVID-19 pandemic was reported by vulnerable groups, while the Icelandic healthcare system managed to maintain accessible services to individuals with COVID-19. [ABSTRACT FROM AUTHOR]

Background Adolescent and young adult cancer survivors (AYAs, aged 18-39 years at first diagnosis) have a higher second cancer risk. Accelerated aging is hypothesized as underlying mechanism and has been described clinically by 6 indicators; fatigue, low quality of sleep, low mood, lack of motivation, subjective memory complaints, and poor exercise tolerance. Using patient-reported outcomes, we aimed to identify clusters of accelerated aging among AYA cancer survivors and to investigate their association with second cancer development. Patients and Methods Patient, tumor, and treatment data were obtained from the Netherlands Cancer Registry. Patient-reported clinical indicators and second cancer data were obtained from the SURVivors (5-20 years) of cancer in AYAs (SURVAYA) questionnaire study between 1999 and 2015. Latent class and multivariable logistic regression analyses were performed. Results In total, n  = 3734 AYA survivors with known second cancer status (n  = 278 [7.4%] second cancers) were included. Four latent clusters were identified and named based on their clinical indicator features; (1) high accelerated aging (31.3%), (2) intermediate accelerated aging without poor exercise tolerance (15.1%), (3) intermediate accelerated aging without lack of motivation (27.4%), and (4) low accelerated aging (26.2%). AYAs in the high accelerated aging cluster were more likely to have second cancer (odds ratio: 1.6; 95% CI, 1.1-2.3) compared to the low accelerated aging cluster. Conclusion AYAs with a higher burden of accelerated aging were more likely to develop a second cancer. Validation of the clinical indicators and how to best capture them is needed to improve (early) detection of AYAs at high risk of developing second cancer. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to establish the test–retest reliability of metrics obtained from wearable inertial sensors that reflect turning performance during tasks designed to imitate various turns in daily activity. Methods Seventy-one adults who were healthy completed 3 turning tasks: a 1-minute walk along a 6-m walkway, a modified Illinois Agility Test (mIAT), and a complex turning course (CTC). Peak axial turning and rotational velocity (yaw angular velocity) were extracted from wearable inertial sensors on the head, trunk, and lumbar spine. Intraclass correlation coefficients (ICCs) were established to assess the test–retest reliability of average peak turning speed for each task. Lap time was collected for reliability analysis as well. Results Turning speed across all tasks demonstrated good to excellent reliability, with the highest reliability noted for the CTC (45-degree turns: ICC = 0.73–0.81; 90-degree turns: ICC = 0.71–0.83; and 135-degree turns: ICC = 0.72–0.80). The reliability of turning speed during 180-degree turns from the 1-minute walk was consistent across all body segments (ICC = 0.74–0.76). mIAT reliability ranged from fair to excellent (end turns: ICC = 0.52–0.72; mid turns: ICC = 0.50–0.56; and slalom turns: ICC = 0.66–0.84). The CTC average lap time demonstrated good test–retest reliability (ICC = 0.69), and the mIAT average lap time test–retest reliability was excellent (ICC = 0.91). Conclusion Turning speed measured by inertial sensors is a reliable outcome across a variety of ecologically valid turning tasks that can be easily tested in a clinical environment. Impact Turning performance is a reliable and important measure that should be included in clinical assessments and clinical trials. [ABSTRACT FROM AUTHOR]

Advancements in genomics have significant implications for public health, making citizens' education vital for informed decision-making. Based on two literature reviews' findings and a survey conducted with experts from the Italian Network of Genomics in Public Health, we conducted a pilot survey on Italian citizens' attitudes, knowledge and educational needs toward genetic testing and omics sciences. Our results demonstrate a widespread interest in genetic testing and uncertainties regarding associated risks, with 99% of participants acknowledging insufficient knowledge of genetic testing. There is an urgent need for educational tools to improve citizens' literacy and engagement in this rapidly evolving field. [ABSTRACT FROM AUTHOR]

Background The MONARCH 2 trial (NCT02107703) showed the efficacy of abemaciclib, a cyclin-dependent kinase 4 & 6 inhibitor (CDK4/6i), in combination with fulvestrant for hormone receptor-positive, HER2-negative metastatic breast cancer (MBC). The aim of this analysis was to explore the prediction of circulating tumor cells (CTCs) stratification using machine learning for hypothesis generation of biomarker-driven clinical trials. Patients and Methods Predicted CTCs were computed in the MONARCH 2 trial through a K nearest neighbor (KNN) classifier trained on a dataset comprising 2436 patients with MBC. Patients were categorized into predicted Stage IVaggressive (pStage IVaggressive, ≥5 predicted CTCs) or predicted Stage IVindolent (pStage IVindolent, <5 predicted CTCs). Prognosis was tested in terms of progression-free-survival (PFS) and overall survival (OS) through Cox regression. Results Patients classified as predicted pStage IVaggressive and predicted pStage Stage IVindolent were, respectively, 183 (28%) and 461 (72%). After multivariable Cox regression, predicted CTCs were confirmed as independently associated with prognosis in terms of OS, together with ECOG performance status, liver involvement, bone-only disease, and treatment arm. Patients in the pStage Stage IVindolent subgroup treated with abemaciclib experienced the best prognosis both in terms of PFS and OS. The treatment effect of abemaciclib on OS was then explored through subgroup analysis, showing a consistent benefit across all subgroups. Conclusion This study is the first analysis of CTCs modeling for stage IV disease stratification. These results show the need to expand biomarker profiling in combination with CTCs stratification for improved biomarker-driven drug development. [ABSTRACT FROM AUTHOR]

Background This study examined the trends and patterns of opioid and non-opioid pharmacotherapy use among a large national sample of privately insured pediatric patients with cancer in the United States. Materials and Methods We identified pediatric (aged < 21) patients diagnosed with central nervous system (CNS), lymphoma, gonadal, leukemia, or bone cancer from MarketScan data 2005-2019. We examined the proportion of patients who filled a prescription for the following 5 types of pharmacotherapy: opioid, anticonvulsant, non-steroidal anti-inflammatory drug (NSAID), antidepressant, and muscle relaxant during active cancer treatment. We assessed the trends and patterns in pharmacotherapy using multivariable logistic regressions. Results Among 4174 patients included, 2979 (71%) had an opioid prescription; 746 (18%), 384 (9%), 202 (5%), and 169 (4%) had anticonvulsant, NSAID, antidepressant and muscle relaxant prescriptions, respectively. Multivariable logistic regression showed a nonlinear trend in the use of opioids among pediatric patients with cancer over time such that use slightly increased until 2012 (OR of 1.40 [95% CI, 1.12-1.73] for 2012 vs. 2006) but then decreased thereafter (OR of 0.51 [0.37-0.68] for 2018 vs. 2012). The use of anticonvulsants, NSAIDs, and muscle relaxants increased significantly linearly over time (all P  < .005). Conclusion There has been a downward trend in the use of opioids in recent years among pediatric patients with cancer and an upward trend in the use of non-opioid pharmacotherapy for pain management potentially as an alternative to opioids. [ABSTRACT FROM AUTHOR]