Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women's Health Initiative.

BACKGROUND: In the Women's Health Initiative (WHI) randomized trial, dietary intervention significantly reduced breast cancer mortality, especially in women with more metabolic syndrome (MetS) components. Therefore, this study investigated the associations of MetS and obesity with postmenopausal breast cancer after long-term follow-up in the WHI clinical trials. METHODS: A total of 68,132 postmenopausal women, without prior breast cancer and with normal mammogram, were entered into WHI randomized clinical trials; 63,330 women with an entry MetS score comprised the study population. At entry, body mass index (BMI) was determined; MetS score (0, 1-2, and 3-4) included the following: (1) high waist circumference (≥88 cm), (2) high blood pressure (systolic ≥130 mm Hg and/or diastolic ≥85 mm Hg, or hypertension history), (3) high-cholesterol history, and (4) diabetes history. Study outcomes included breast cancer incidence, breast cancer mortality, deaths after breast cancer, and results by hormone receptor status. RESULTS: After a >20-year mortality follow-up, a higher MetS score (3-4), adjusted for BMI, was significantly associated with more poor prognosis, estrogen receptor (ER)-positive, progesterone receptor (PR)-negative cancers (p = .03), 53% more deaths after breast cancer (p < .001), and 44% higher breast cancer mortality (p = .03). Obesity status, adjusted for MetS score, was significantly associated with more good prognosis, ER-positive, PR-positive cancers (p < .001), more total breast cancers (p < .001), and more deaths after breast cancer (p < .001), with higher breast cancer mortality only in women with severe obesity (BMI, ≥35 kg/m2; p < .001). CONCLUSIONS: MetS and obesity status have independent, but differential, adverse associations with breast cancer receptor subtypes and breast cancer mortality risk. Both represent separate targets for breast cancer prediction and prevention strategies.

Uptake of screening and risk-reducing recommendations among women with hereditary breast and ovarian cancer syndrome due to pathogenic BRCA1/2 variants evaluated at a large urban comprehensive cancer center.

PURPOSE: Carriers of pathogenic variants in BRCA1/2 have an elevated lifetime cancer risk warranting high-risk screening and risk-reducing procedures for early detection and prevention. We report on prevention practices among women with pathogenic BRCA variants in order to document follow through with NCCN recommendations and to identify barriers to guideline-recommended care. METHODS: Our cohort included women who had genetic testing through a cancer genetic clinic and completed a 54-item questionnaire to measure socio-demographics, medical history, rates of cancer screening and risk-reducing surgery, disclosure of test results, and cancer worry. Outcomes included rates of completion of risk-reducing salpingo-oophorectomy (RRSO), risk-reducing mastectomy (RRM), and NCCN risk-reducing and age-dependent screening guidelines (version 3.2019). Multivariable logistic regression analyses were used to evaluate potential predictors of these outcomes. RESULTS: Of 129 evaluable women with pathogenic BRCA1/2 variants, 95 (74%) underwent RRSO and 77 (60%) had RRM, respectively, and 107 (83%) were considered adherent to NCCN guidelines. Women with a history of breast or ovarian cancer were more likely to have RRM (OR = 4.38; 95% CI 1.80-11.51; p = 0.002). Increasing age was associated with an increased likelihood of RRSO (OR = 1.05; 95% CI 1.01-1.09; p = 0.019) and decreased likelihood for RRM (OR = 0.95; 95% CI 0.92-0.99; p = 0.013). Women who had RRM were 3 times more likely to undergo RRSO (OR = 2.81; 95% CI 1.10-7.44; p = 0.025). Women who had genetic testing after June 2013 were less likely to have RRM than those tested before June 2013 (OR = 0.42; 95% CI 0.18-0.95; p = 0.040. None of the other measured factors were associated with rates of RRSO, RRM or follow through with NCCN recommendations. There was near universal (127/129) reported disclosure of genetic test results to family members, resulting in the discovery of a median of 1 relative with a pathogenic variant (range = 0-8). CONCLUSION: An evaluation of follow up practice in a cohort of women with pathogenic variants in BRCA1/2 revealed high rates of reported completion of screening and surgical risk-reducing recommendations. Educational efforts should continue to reinforce the importance of follow-through with guideline recommended care among this high-risk group.

Ductal carcinoma in situ and cause-specific mortality among younger and older postmenopausal women: the Women's Health Initiative.

BACKGROUND: Whether DCIS is associated with higher breast cancer-specific and all-cause mortality is unclear with few studies in older women. Therefore, we examined DCIS and breast cancer-specific, cardiovascular (CVD)-specific, and all-cause mortality among Women's Health Initiative (WHI) Clinical Trial participants overall and by age (< 70 versus ≥ 70 years). METHODS: Of 68,132 WHI participants, included were 781 postmenopausal women with incident DCIS and 781 matched controls. Serial screening mammography was mandated with high adherence. DCIS cases were confirmed by central medical record review. Adjusted multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Kaplan Meier (KM) plots were used to assess 10-year and 20-year mortality rates. RESULTS: After 20.3 years total, and 13.2 years median post-diagnosis follow-up, compared to controls, DCIS was associated with higher breast cancer-specific mortality (HR 3.29; CI = 1.32-8.22, P = 0.01). The absolute difference in 20-year breast cancer mortality was 1.2% without DCIS and 3.4% after DCIS, log-rank P = 0.026. Findings were similar by age (< 70 versus ≥ 70 years) with no interaction (P interaction = 0.80). Incident DCIS was not associated with CVD-specific mortality (HR 0.77; CI-0.54-1.09, P = 0.14) or with all-cause mortality (HR 0.96; CI = 0.80-1.16, P = 0.68) with similar findings by age. CONCLUSIONS: In postmenopausal women, incident DCIS was associated with over three-fold higher breast cancer-specific mortality, with similar findings in younger and older postmenopausal women. These finding suggest caution in using age to adjust DCIS clinical management or research strategies.

Safety and efficacy of linaclotide in children aged 7-17 years with irritable bowel syndrome with constipation.

OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for the treatment of children 6-17 years old with functional constipation. This study evaluated the safety and efficacy of various linaclotide doses in children 7-17 years old with irritable bowel syndrome with constipation (IBS-C). METHODS: In this 4-week, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study, children with IBS-C were randomized to once-daily placebo or linaclotide (Dose A: 18 or 36 µg, B: 36 or 72 µg, and C: 72 µg or 145 µg, or 290 µg); those aged 7-11 years in a 1:1:1:1 allocation based on weight (18 to <35 kg:18 µg, 36 µg, or 72 µg; or ≥35 kg: 36 µg, 72 µg, or 145 µg), and those aged 12-17 years in a 1:1:1:1:1 allocation (the higher option of Doses A-C or 290 µg). The primary efficacy endpoint was a change from baseline in 4-week overall spontaneous bowel movement (SBM) frequency rate over the treatment period. Adverse events and clinical laboratory measures were also assessed. RESULTS: Efficacy, safety, and tolerability were assessed in 101 patients. In the intent-to-treat population, numerical improvement was observed in overall SBM frequency rate with increasing linaclotide doses (A: 1.62, B: 1.52, and C: 2.30, 290 µg: 3.26) compared with placebo. The most reported treatment-emergent adverse events were diarrhea and pain, with most cases being mild and none being severe. CONCLUSIONS: Linaclotide was tolerated well in this pediatric population, showing numerical improvement in SBM frequency compared with placebo.

Randomized controlled trial of linaclotide in children aged 6-17 years with functional constipation.

OBJECTIVES: Linaclotide, a guanylate cyclase-C agonist, was recently approved in the United States for treatment of children 6-17 years old with functional constipation (FC). This study evaluated the safety and efficacy of several linaclotide doses in children 6-17 years old with FC. METHODS: In this multicenter, randomized, double-blind, placebo-controlled phase 2 study, 173 children with FC (based on Rome III criteria) were randomized to once-daily linaclotide (A: 9 or 18 µg, B: 18 or 36 µg, or C: 36 or 72 µg) or placebo in a 1:1:1:1 ratio for 6- to 11-year-olds (dosage determined by weight: 18 to <35 or ≥35 kg) and linaclotide (18, 36, 72, or 145 µg) or placebo in a 1:1:1:1:1 ratio for 12- to 17-year-olds. The primary efficacy endpoint was change from baseline in weekly spontaneous bowel movement (SBM) frequency throughout the 4-week treatment period. Adverse events (AE), clinical laboratory values, and electrocardiograms were monitored. RESULTS: Efficacy and safety were assessed in 173 patients (52.0% aged 6-11 years; 48.0% aged 12-17 years); 162 (93.6%) completed the treatment period. A numerical improvement in mean SBM frequency was observed with increasing linaclotide doses (1.90 in 6- to 11-year-olds [36 or 72 µg] and 2.86 in 12- to 17-year-olds [72 µg]). The most reported treatment-emergent AE was diarrhea, with most cases being mild; none were severe. CONCLUSIONS: Linaclotide was well tolerated in this pediatric population, with a trend toward efficacy in the higher doses, warranting further evaluation.

How external and agency characteristics are related to coordination in homecare - findings of the national multicenter, cross-sectional SPOTnat study.

BACKGROUND: Homecare client services are often distributed across several interdependent healthcare providers, making proper care coordination essential. However, as studies exploring care coordination in the homecare setting are scarce, serious knowledge gaps exist regarding how various factors influence coordination in this care sector. To fill such gaps, this study's central aim was to explore how external factors (i.e., financial and regulatory mechanisms) and homecare agency characteristics (i.e., work environment, workforce, and client characteristics) are related to care coordination in homecare. METHODS: This analysis was part of a national multicentre, cross-sectional study in the Swiss homecare setting that included a stratified random sample of 88 Swiss homecare agencies. Data were collected between January and September 2021 through agency and employee questionnaires. Using our newly developed care coordination framework, COORA, we modelled our variables to assess the relevant components of care coordination on the structural, process, and outcome levels. We conducted both descriptive and multilevel regression analyses-with the latter adjusting for dependencies within agencies-to explore which key factors are associated with coordination. RESULTS: The final sample size consisted of 1450 employees of 71 homecare agencies. We found that one explicit coordination mechanism ("communication and information exchange" (beta = 0.10, p <.001)) and four implicit coordination mechanisms-"knowledge of the health system" (beta = -0.07, p <.01), "role clarity" (beta = 0.07, p <.001), "mutual respect and trust" (beta = 0.07, p <.001), and "accountability, predictability, common perspective" (beta = 0.19, p <.001)-were significantly positively associated with employee-perceived coordination. We also found that the effects of agency characteristics and external factors were mediated through coordination processes. CONCLUSION: Implicit coordination mechanisms, which enable and enhance team communication, require closer examination. While developing strategies to strengthen implicit mechanisms, the involvement of the entire care team is vital to create structures (i.e., explicit mechanisms) that enable communication and information exchange. Appropriate coordination processes seem to mitigate the association between staffing and coordination. This suggests that they support coordination even when workload and overtime are higher.

How regulatory frameworks drive differences in home-care agencies: Results from a national multicenter cross-sectional study in Switzerland.

INTRODUCTION: The sustainability and rising costs of the health-care system are of concern. Although health-care reforms impact various areas of care, there is only limited evidence on how regulations affect home-care agencies and health-care delivery. OBJECTIVES: The primary aim was to explore different financial and regulatory mechanisms and how they drive differences in the organizational structures, processes, and work environment of home-care agencies. DESIGN AND METHODS: We used data from a national multicenter cross-sectional study of Swiss home care that included a random sample of 88 home-care agencies with a total of 3223 employees. Data was collected in 2021 through agency and personnel questionnaires including geographic characteristics, financial and regulatory mechanisms, service provision, financing, work environment, resources and time allocation, and personnel recruitment. We first conducted a cluster analysis to build agency groups with similar financial and regulatory mechanisms. We then performed Fisher's exact, ANOVA, and Kruskal-Wallis tests to determine group differences in organizational structures, processes, and work environments. Finally, we performed a lasso regression to determine which variables were predictive for the groups. RESULTS: Four agency groups were built, differing in view of financial and regulatory mechanisms and we found differences in the range and amount of services provided, with regard to employment conditions and cost structures. DISCUSSION: The most prominent differences were found between agency groups with versus agency groups without a service obligation. Financial incentives must be well aligned with the goal of achieving and maintaining financially sustainable, accessible, and high-quality home care.

Periocular Asymmetry Index in Caucasian Populations Using Three-dimensional Photogrammetry Assessment.

OBJECTIVE: To quantitatively assess the periocular asymmetry and investigate its sex and age-related differences in a Caucasian population using three-dimensional (3D) stereophotogrammetry. METHOD: Standardized 3D photos of the periocular region of 301 Caucasians were taken using the VECTRA M3 3D Imaging System. Standardized landmarks were positioned, and data measurements in the periocular region were obtained from these images using VAM software and assessed using intraclass correlation coefficients (ICC) for reliability. Absolute differences and asymmetry index between the right and the left periocular region were calculated with a focus on gender and age-related differences. RESULT: Fissure height asymmetry was positively correlated with age (p < 0.01). Furthermore, reflex distance asymmetry was positively correlated with age in the elderly group (p < 0.05). Absolute differences of upper eyelid crease were 0.65 ± 0.79 mm for females and 0.90 ± 0.94 mm for males (p < 0.05). In the elderly group, the absolute differences of reflex distance were 0.664 ± 0.471 mm for males and 0.470 ± 0.408 mm for females (p < 0.05), while the absolute differences of fissure height were 0.619 ± 0.469 mm and 0.436 ± 0.372 mm, respectively (p < 0.05). All measurements had an inter-rater ICC and intra-rater ICC between 0.761 and 0.957. CONCLUSION: Periocular asymmetry is more prominent in older and male people. 3D photogrammetry is a reliable tool to detect periocular asymmetry and might provide an accurate and effective reference for periocular cosmetic, plastic, and reconstructive surgery in the clinical routine. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors. www.springer.com/00266 .

Setting new priorities for nursing research: The updated Swiss Nursing Research Agenda-a systematic, participative approach.

AIM: To identify current key areas for nursing research in Switzerland, we revised the Swiss Research Agenda for Nursing (SRAN) initially published in 2008. BACKGROUND: By developing a research agenda, nursing researchers internationally prioritize and cluster relevant topics within the research community. The process should be collaborative and systematic to provide credible information for decisionmakers in health care research, policy, and practice. SOURCES OF EVIDENCE: After a participative, systematic, and critical evaluation within and outside of the Swiss Association for Nursing Science, the updated SRAN 2019-2029 defines four research priorities (new models of care, nursing care interventions, work and care environment, and quality of care and patient safety) and four transversal themes (organization of research, research methodologies, research in health care policy and public health perspectives). CONCLUSION: Adding to other national nursing research agendas, the categories are organized in a framework of key research priorities and transversal themes. They relate to the importance of global and local foci of research as well as challenges in health care services and policy systems. The agenda is an important prerequisite for enhancing the influence of nursing research in Switzerland and provides guidance for the next decade. IMPLICATIONS FOR NURSING PRACTICE: The revised agenda ensures that research projects target key knowledge gaps and the discipline's core questions in respective countries. IMPLICATIONS FOR HEALTH POLICY: Nursing research should inform and influence health policy on all institutional and political levels. Therefore, the integration of public health perspectives in research is one of the most important new aspects of SRAN 2019-2029.

Racial and ethnic variation in BRCA1 and BRCA2 genetic test results among individuals referred for genetic counseling at a large urban comprehensive cancer center.

PURPOSE: The prevalence of pathogenic variants in BRCA1 and BRCA2 in populations other than Ashkenazi Jewish (AJ) is not well defined. We describe the racial and ethnic-specific prevalence of BRCA1/2 pathogenic variants and variants of uncertain significance (VUS) among individuals referred for genetic testing in a large urban comprehensive cancer center over a 20-year period. METHODS: The population included 3,537 unrelated individuals who underwent genetic testing from January 1999 to October 2019 at the Karmanos Cancer Institute. We estimated the prevalence of pathogenic variants and VUS and evaluated associations with race and ethnicity for African American (AA), Arab, AJ and Hispanic individuals compared to Non-Hispanic Whites (NHW). We used multivariable models to adjust for other predictors of pathogenic variants. We also reported the most common pathogenic variants by racial and ethnic group. RESULTS: The racial and ethnic breakdown of our population was: NHW (68.9%), AA (20.3%), AJ (2.5%), Arab (2.2%), Hispanic (1.0%), Asian Pacific Islander, Native American/Alaskan Native (4.7%), and < 1% unknown. The overall prevalence of pathogenic variants in BRCA1/2 was 8.9% and the prevalence of VUS was 5.6%. Compared to NHW, there were no racial or ethnic differences in the rate of pathogenic variants. However, AA individuals were more likely to have VUS in BRCA1 (adjusted OR 2.43, 95% CI 1.38-4.28) and AJ were more likely to have VUS in BRCA2 (adjusted OR 3.50, 95% CI 1.61-6.58). CONCLUSION: These results suggest the continued need for genetic testing and variant reclassification for individuals of all racial and ethnic groups.

Chemotherapy-induced peripheral neuropathy in the detroit research on cancer survivors (ROCS) cohort.

PURPOSE: Improved life expectancy has increased the likelihood for long-term complications from chemotherapy among cancer survivors. One burdensome complication is chemotherapy-induced peripheral neuropathy (CIPN). We evaluated rates of CIPN outcomes in the Detroit Research on Cancer Survivorship (ROCS) cohort. METHODS: The population included 1,034 African American (AA) survivors who received chemotherapy for breast, colorectal, lung or prostate cancer. CIPN prevalence was based on initial occurrence of worsening of self-reported pain, numbness or tingling after chemotherapy. Current CIPN included symptoms still present at the time of the survey, and persistent CIPN symptoms were present 12 or more months post-chemotherapy. CIPN severity was ranked as mild, moderate or severe. Logistic regression was utilized to evaluate sociodemographic and clinical factors associated with the various categories of CIPN. RESULTS: CIPN prevalence was 68%, with 53% current and 52% persistent. The symptom severity distribution based on prevalent CIPN included 32.2% mild, 30.8% moderate, and 36.9% severe. Factors associated with prevalent CIPN (odds ratio, 95% confidence interval) included primary cancer site (breast: 3.88, 2.02-7.46); and (colorectal: 5.37, 2.69-10.73), lower risk for older age at diagnosis (0.66, 0.53-0.83) and divorced/separated marital status (2.13, 1.42-3.21). Current CIPN was in addition, associated with more advanced stage disease trend (1.34, 1.08-1.66) and greater number of co-morbid medical conditions trend (1.23, 1.09-1.40), as was persistent CIPN. Severity of prevalent CIPN was associated with history of arthritis (1.55, 1.06-2.26) and severity of persistent CIPN with higher BMI (1.58, 1.07-2.35). CONCLUSIONS: CIPN is a common and persistent complication in AA cancer survivors. Further research is needed to improve our understanding of CIPN predictors in all groups of cancer survivors.

Proton Pump Inhibitor Use and Obesity-Associated Cancer in the Women's Health Initiative.

Proton pump inhibitors (PPIs) have off-target activity on fatty acid synthase (FASN), a critical enzyme in energy balance and cancer growth. We evaluated risk of common obesity-related cancers: breast, colorectal (CRC), and endometrial, with use of PPI and histamine-2 receptor antagonists (H2RA) in 124,931 postmenopausal women enrolled in the Women's Health Initiative. Incident cancer cases were physician-adjudicated. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for cancer incidence after year 3. There were 7956 PPI ever users and 9398 H2RA only users. Ever use of either PPI or H2RA was not associated with risk of breast cancer (n = 9186) nor risk of endometrial cancer (n = 1231). The risk of CRC (n = 2280) was significantly lower in PPI users (HR = 0.75, 95% CI = 0.61-0.92), but not in H2RA users (HR = 1.13, 95% CI = 0.97-1.31). The association of PPI use with CRC was apparent regardless of BMI or NSAID use, and was stronger with longer PPI duration (p = 0.006) and potency (p = 0.005). The findings that PPI use, but not H2RA use, demonstrate an inverse dose-response relationship with risk of CRC is consistent with preclinical data showing FASN inhibition prevents colon cancer progression and supports a role of PPI in CRC prevention.

Quadrivalent meningococcal tetanus toxoid-conjugate booster vaccination in adolescents and adults: phase III randomized study.

BACKGROUND: The immunogenicity and safety of a booster dose of tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT), alone or co-administered with MenB vaccine, were assessed in healthy 13-25-year olds who received MenACYW-TT or a CRM-conjugate vaccine (MCV4-CRM) 3-6 years earlier. METHODS: This phase IIIb open-label trial (NCT04084769) evaluated MenACYW-TT-primed participants, randomized to receive MenACYW-TT alone or with a MenB vaccine, and MCV4-CRM-primed participants who received MenACYW-TT alone. Functional antibodies against serogroups A, C, W and Y were measured using human complement serum bactericidal antibody assay (hSBA). The primary endpoint was vaccine seroresponse (post-vaccination titers ≥1:16 if pre-vaccination titers <1:8; or a ≥4-fold increase if pre-vaccination titers ≥1:8) 30 days post booster. Safety was evaluated throughout the study. RESULTS: The persistence of the immune response following primary vaccination with MenACYW-TT was demonstrated. Seroresponse after MenACYW-TT booster was high regardless of priming vaccine (serogroup A: 94.8% vs 93.2%; C: 97.1% vs 98.9%; W: 97.7% vs 98.9%; and Y; 98.9% vs 100% for MenACWY-TT-primed and MCV4-CRM-primed groups, respectively). Co-administration with MenB vaccines did not affect MenACWY-TT immunogenicity. No vaccine-related serious adverse events were reported. CONCLUSIONS: MenACYW-TT booster induced robust immunogenicity against all serogroups, regardless of the primary vaccine received, and had an acceptable safety profile. IMPACT: A booster dose of MenACYW-TT induces robust immune responses in children and adolescents primed with MenACYW-TT or another MCV4 (MCV4-DT or MCV4-CRM), respectively. Here, we demonstrate that MenACYW-TT booster 3-6 years after primary vaccination induced robust immunogenicity against all serogroups, regardless of the priming vaccine (MenACWY-TT or MCV4-CRM), and was well tolerated. Persistence of the immune response following previous primary vaccination with MenACYW-TT was demonstrated. MenACYW-TT booster with MenB vaccine co-administration did not affect MenACWY-TT immunogenicity and was well tolerated. These findings will facilitate the provision of broader protection against IMD particularly in higher-risk groups such as adolescents.

The unrecognized role of fidelity in effectiveness-implementation hybrid trials: simulation study and guidance for implementation researchers.

BACKGROUND: Effectiveness-implementation hybrid designs are a relatively new approach to evaluate efficacious interventions in real-world settings while concurrently gathering information on the implementation. Intervention fidelity can significantly influence the effectiveness of an intervention during implementation. However little guidance exists for applied researchers conducting effectiveness-implementation hybrid trials regarding the impact of fidelity on intervention effects and power. METHODS: We conducted a simulation study based on parameters from a clinical example study. For the simulation, we explored parallel and stepped-wedge cluster randomized trials (CRTs) and hypothetical patterns of fidelity increase during implementation: slow, linear, and fast. Based on fixed design parameters, i.e., the number of clusters (C = 6), time points (T = 7), and patients per cluster (n = 10) we used linear mixed models to estimate the intervention effect and calculated the power for different fidelity patterns. Further, we conducted a sensitivity analysis to compare outcomes based on different assumptions for the intracluster-correlation coefficient and the cluster size. RESULTS: Ensuring high fidelity from the beginning is central to achieve accurate intervention effect estimates in stepped-wedge and parallel CRTs. The importance of high fidelity in the earlier stages is more emphasized in stepped-wedge designs than in parallel CRTs. In contrast, if the increase of fidelity is too slow despite relatively high starting levels, the study will likely be underpowered and the intervention effect estimates will also be biased. This effect is more accentuated in parallel CRTs, here reaching 100% fidelity within the next measurement points is crucial. CONCLUSIONS: This study discusses the importance of intervention fidelity for the study`s power and highlights different recommendations to deal with low fidelity in parallel and stepped-wedge CRTs from a design perspective. Applied researchers should consider the detrimental effect of low fidelity in their evaluation design. Overall, there are fewer options to adjust the trial design after the fact in parallel CRT as compared to stepped-wedge CRTs. Particular emphasis should be placed on the selection of contextually relevant implementation strategies.

Administrative burden in Swiss nursing homes and its association with care workers' outcomes-a multicenter cross-sectional study.

BACKGROUND: Care workers in nursing homes often perform tasks that are rather related to organizational or management activities than 'direct patient care'. 'Indirect care activities', such as documentation or other administrative tasks are often considered by care workers as a burden, as they increase overall workload and keep them away from caring for residents. So far, there is little investigation into what kind of administrative tasks are being performed in nursing homes, by which type of care workers, and to which extent, nor how administrative burden is associated with care workers' outcomes. PURPOSE: The objective of this study was to describe care workers' administrative burden in Swiss nursing homes and to explore the association with four care worker outcomes (i.e., job dissatisfaction, emotional exhaustion, intention to leave the current job and the profession). METHODS: This multicenter cross-sectional study used survey data from the Swiss Nursing Homes Human Resources Project 2018. It included a convenience sample of 118 nursing homes and 2'207 care workers (i.e., registered nurses, licensed practical nurses) from Switzerland's German- and French-speaking regions. Care workers completed questionnaires assessing the administrative tasks and burden, staffing and resource adequacy, leadership ability, implicit rationing of nursing care and care worker characteristics and outcomes. For the analysis, we applied generalized linear mixed models, including individual-level nurse survey data and data on unit and facility characteristics. RESULTS: Overall, 73.9% (n = 1'561) of care workers felt strongly or rather strongly burdened, with one third (36.6%, n = 787) reporting to spend 2 h or more during a "normal" day performing administrative tasks. Ratings for administrative burden ranged from 42.6% (n = 884; ordering supplies and managing stocks) to 75.3% (n = 1'621; filling out the resident's health record). One out of four care workers (25.5%, n = 561) intended to leave the profession, whereby care workers reporting higher administrative task burden (OR = 1.24; 95%CI: 1.02-1.50) were more likely to intend to leave the profession. CONCLUSION: This study provides first insights on care workers' administrative burden in nursing homes. By limiting care workers' burdensome administrative tasks and/or shifting such tasks from higher to lower educated care workers or administrative personnel when appropriate, nursing home managers could reduce care workers' workload and improve their job satisfaction and retention in the profession.

Evaluating the implementation fidelity to a successful nurse-led model (INTERCARE) which reduced nursing home unplanned hospitalisations.

BACKGROUND: Implementation fidelity assesses the degree to which an intervention is delivered as it should be. Fidelity helps to determine if the outcome(s) of an intervention are attributed to the intervention itself or to a failure of its implementation. Little is known about how fidelity impacts the intended outcome(s) and what elements or moderators can affect the fidelity trajectory over time. We exemplify the meaning of implementation fidelity with INTERCARE, a nurse-led care model that was implemented in eleven Swiss nursing homes (NHs) and showed effectiveness in reducing unplanned hospital transfers. INTERCARE comprises six core elements, including advance care planning and tools to support inter- and interprofessional communication, which were introduced with carefully developed implementation strategies. METHODS: A mixed-methods convergent/triangulation design was used to investigate the influence of implementation fidelity on unplanned transfers. A fidelity questionnaire measuring the degree of fidelity to INTERCARE's core components was fielded at four time points in the participating NHs. Two-monthly meetings were conducted with NHs (September 2018-January 2020) and structured notes were used to determine moderators affecting fidelity (e.g., participant responsiveness). We used the fidelity scores and generalized linear mixed models to analyze the quantitative data. The Framework method was used for the qualitative analysis. The quantitative and qualitative findings were integrated using triangulation. RESULTS: A higher overall fidelity score showed a decreasing rate of unplanned hospital transfers post-intervention (OR: 0.65 (CI = 0.43-0.99), p = 0.047). A higher fidelity score to advance care planning was associated with lower unplanned transfers (OR = 0.24 (CI 0.13-0.44), p = < 0.001) and a lower fidelity score for communication tools (e.g., ISBAR) to higher rates in unplanned transfers (OR = 1.69 (CI 1.30-2.19), p = < 0.003). In-house physicians with a collaborative approach and staff's perceived need for nurses working in extended roles, were important moderators to achieve and sustain high fidelity. CONCLUSION: Implementation fidelity is challenging to measure and report, especially in complex interventions, yet is crucial to better understand how such interventions may be tailored for scale-up. This study provides both a detailed description of how fidelity can be measured and which ingredients highly contributed to reducing unplanned NH transfers. TRIAL REGISTRATION: The INTERCARE study was registered at clinicaltrials.gov Protocol Record NCT03590470.

Identifying work-related factors associated with work-family conflict of care workers in nursing homes: A cross-sectional study.

AIMS: To investigate which work-related factors are associated with work-family conflict of care workers in nursing homes, this study aimed to: (a) describe the prevalence of work-family conflict of care workers in nursing homes and (b) assess the association of work-related factors with work-family conflict. DESIGN: Cross-sectional multicentre sub-study based on data from the Swiss Nursing Homes Human Resources Project 2018. METHODS: Data were collected between September 2018 and October 2019. Work-family conflict of care workers was assessed with the Work-Family Conflict Scale (range 1-5). Prevalence was described in percentages. We used multilevel linear regression to assess the association of time-based factors (working overtime or during one's free time, employment percentage, presenteeism, shift working) and strain-based factors (staffing adequacy, leadership support) with work-family conflict. RESULTS: Our study sample consisted of 4324 care workers working in a total of 114 nursing homes. Overall, 31.2% of respondents stated to have experienced work-family conflict (>3.0 on the Work-Family Conflict Scale). The overall mean score of the study sample for work-family conflict was 2.5. Care workers experiencing presenteeism 10 or more days per year showed the highest scores for work-family conflict (mean: 3.1). All included predictor variables were significant (p < .05). CONCLUSION: Work-family conflict is multifactorial. Possible intervention points to tackle work-family conflict could be strengthening care workers' influence in planning work schedules, enabling flexible planning to ensure adequate staffing, lowering presenteeism and implementing a supportive leadership style. IMPACT: Care workers' jobs become less desirable when workplace demands interfere with family life. This study highlights the multifaceted nature of work-family conflict and suggests intervention options to prevent care workers from experiencing work-family conflict. Action is needed at nursing home and policy level.

Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality.

Importance: Approximately 65% of adults in the US consume sugar-sweetened beverages daily. Objective: To study the associations between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality. Design, Setting, and Participants: A prospective cohort with 98 786 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative from 1993 to 1998 at 40 clinical centers in the US and were followed up to March 1, 2020. Exposures: Sugar-sweetened beverage intake was assessed based on a food frequency questionnaire administered at baseline and defined as the sum of regular soft drinks and fruit drinks (not including fruit juice); artificially sweetened beverage intake was measured at 3-year follow-up. Main Outcomes and Measures: The primary outcomes were (1) liver cancer incidence, and (2) mortality due to chronic liver disease, defined as death from nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% CIs for liver cancer incidence and for chronic liver disease mortality, adjusting for potential confounders including demographics and lifestyle factors. Results: During a median follow-up of 20.9 years, 207 women developed liver cancer and 148 died from chronic liver disease. At baseline, 6.8% of women consumed 1 or more sugar-sweetened beverage servings per day, and 13.1% consumed 1 or more artificially sweetened beverage servings per day at 3-year follow-up. Compared with intake of 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more servings per day had a significantly higher risk of liver cancer (18.0 vs 10.3 per 100 000 person-years [P value for trend = .02]; adjusted HR, 1.85 [95% CI, 1.16-2.96]; P = .01) and chronic liver disease mortality (17.7 vs 7.1 per 100 000 person-years [P value for trend <.001]; adjusted HR, 1.68 [95% CI, 1.03-2.75]; P = .04). Compared with intake of 3 or fewer artificially sweetened beverages per month, individuals who consumed 1 or more artificially sweetened beverages per day did not have significantly increased incidence of liver cancer (11.8 vs 10.2 per 100 000 person-years [P value for trend = .70]; adjusted HR, 1.17 [95% CI, 0.70-1.94]; P = .55) or chronic liver disease mortality (7.1 vs 5.3 per 100 000 person-years [P value for trend = .32]; adjusted HR, 0.95 [95% CI, 0.49-1.84]; P = .88). Conclusions and Relevance: In postmenopausal women, compared with consuming 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more sugar-sweetened beverages per day had a higher incidence of liver cancer and death from chronic liver disease. Future studies should confirm these findings and identify the biological pathways of these associations.

Quantifying Dermatochalasis Using 3-Dimensional Photogrammetry.

BACKGROUND: Creating an appropriate treatment plan for patients with dermatochalasis requires careful investigation of the periocular region. Utilizing photographic documentation can assist physicians in conducting preoperative analysis and managing expectations regarding surgical outcomes. OBJECTIVES: This study aimed to quantify the periocular characteristics of dermatochalasis patients using standardized 3D imaging and to compare age and sex-related changes in periocular features. METHODS: In this cross-sectional study, we recruited 145 Caucasian patients with periocular dermatochalasis, comprising 48 men and 97 women, aged between 35 and 91 years. Standardized three-dimensional facial photographs were taken using the 3D Imaging system VECTRA M3. Linear dimensions, curve length, angle, indices, and sizes were measured and analyzed, including palpebral fissure height (PFH), palpebral fissure width (PFW), upper lid fold-palpebral margin distance (FPD), upper palpebral margin length (UPML), lower palpebral margin length (LPML), canthal tilt (CT), palpebral fissure index (PFI), upper eyelid area, and ocular surface area. RESULTS: In the female group, the left-side PFH was slightly larger than the right-side PFH (P = 0.023), but the difference was less than 1mm. The corresponding PFI also showed a difference in the female group (P = 0.009). Statistically significant differences were shown in genders for specific parameters, except PFI (P = 0.251) and CT (P = 0.098). Among males, PFW (R = -0.523, p < 0.001) and LPML (R = -0.514, P = 0.264) decreased moderately with age. The correlation between UPML and age was weak (R = -0.367, P = 0.010). Similarly, among females, moderate correlations were found between age and PFW (R = -0.566, P < 0.001) and LPML (R = -0.537, P < 0.001). Additionally, PFH (R = -0.315, P = 0.002), UPML (R = -0.381, P < 0.001), and ocular surface area (R = -0.457, P < 0.001) showed weak correlations with age. CONCLUSIONS: The study found that dermatochalasis usually affects both eyes simultaneously, and age is a significant factor in the morphological changes of certain periocular features regardless of sex. The PFI is not influenced by age or sex. These findings may provide useful information for surgical planning and understanding age-related changes in the periocular area. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Functional and Sport-Specific Outcome Following Traumatic First-Time Shoulder Dislocation and Arthroscopic Surgical Repair in Rock Climbers.

INTRODUCTION: Traumatic shoulder dislocations rank among the most common shoulder injuries in climbers, with rising numbers over the last years. The objective of this study was to analyze the outcome following traumatic first-time shoulder dislocation and subsequent surgical treatment in this population. METHODS: In a retrospective study, climbers who experienced a traumatic shoulder dislocation were treated with an arthroscopic repair of the labrum-ligament complex (LLC). The functional outcome was assessed with a standardized questionnaire and clinical examination, including the Constant Murley and Single Assessment Numeric Evaluation scores. The sport-specific outcome was analyzed using the Union Internationale des Associations d'Alpinisme (UIAA) scale of difficulty and a sport-specific outcome score. RESULTS: The functional and sport-specific outcome for 27 climbers (20 men; 7 women; 3 with bilateral injuries; age, 34±11 [17-61] y; data presented as mean±SD [range]) was assessed 53±29 (12-103) mo after surgery. The postoperative Constant Murley score was 95±8 (67-100) points. At follow-up, 93% (n=25) of patients had started climbing again. Twenty-one climbers (78%) reached a climbing level within the range of ±0.33 UIAA grades of their initial capability or even exceeded their preinjury grade. Only 7% (n=2) of the patients had a recurrent shoulder dislocation, leading to a secondary surgery, and, therefore, required ongoing postoperative treatment at the time of follow-up. CONCLUSIONS: Arthroscopic repair of the LLC following first-time traumatic shoulder dislocation in climbers shows a good outcome and a low recurrence rate. After surgery, most patients are able to regain a high level of rock-climbing ability.