Generalized Estimating Equations Research Articles

Diminished ovarian reserve may have no effect on embryo euploidy: A retrospective cohort study.

Does an association exist between diminished ovarian reserve (DOR) and embryonic aneuploidy risk in young women of reproductive age? This retrospective cohort study included 854 participants treated in the Department of Reproductive Medicine, Women's Hospital of Nanjing Medicine University, Nanjing Maternity and Child Health Care Hospital, from May 2016 to September 2023 for a total of 894 cycles. The relationship between ovarian reserve and embryonic euploidy was evaluated using statistical methods such as generalized estimating equation (GEE) and propensity score matching (PSM). Despite the higher number of biopsied blastocysts in women with normal ovarian reserve, no significant difference in embryonic aneuploidy rates was observed between DOR women and the control group. In addition, there were no significant disparities observed in the rates of metaphase II (MII) oocytes, normal fertilization, transferable embryos, blastocyst formation, and high-scoring blastocysts between the DOR and control groups after PSM. This study showed that DOR had no significant effect on the incidence of aneuploidy in embryos. Young women informed about DOR should be relatively confident about the quality of their eggs and the euploidy status of their embryos before conventional assisted reproduction, thereby mitigating concern regarding adverse maternal outcomes due to aneuploidy.

Latent class analysis of post-acute sequelae of SARS-CoV-2 infection.

Symptoms post-SARS-CoV-2 infection may persist for months and cause significant impairment and impact to quality of life. Acute symptoms of SARS-CoV-2 infection are well studied, yet data on clusters of symptoms over time, or post-acute sequelae of SARS-CoV-2 infection (PASC), are limited. We aim to characterize PASC phenotypes by identifying symptom clusters over a six-month period following infection in individuals vaccinated (boosted and not) and those unvaccinated. Subjects with ≥1 self-reported symptom and positive RT-PCR for SARS-CoV-2 at CVS Health US test sites were recruited between January and April 2022. Patient-reported outcomes symptoms, health-related quality of life (HRQoL), work productivity and activity impairment (WPAI) were captured at 1 month, 3 months, and 6 months post-acute infection. Phenotypes of PASC were determined based on subject matter knowledge and balanced consideration of statistical criteria (lower AIC, lower BIC, and adequate entropy) and interpretability. Generalized estimation equation approach was used to investigate relationship between QoL, WPAI and number of symptoms and identified phenotypes, and relationship between phenotypes and vaccination status as well. LCA identified three phenotypes that are primarily differentiated by number of symptoms. These three phenotypes remained consistent across time periods. Subjects with more symptoms were associated with lower HRQoL, and worse WPAI scores. Vaccinated individuals were more likely to be in the low symptom burden latent classes at all time points compared to unvaccinated individuals.

Digital Exclusion and Cognitive Function in Elderly Populations in Developing Countries: Insights Derived From 2 Longitudinal Cohort Studies.

Cognition disorders not only lead to adverse health consequences but also contribute to a range of socioeconomic challenges and diminished capacity for performing routine daily activities. In the digital era, understanding the impact of digital exclusion on cognitive function is crucial, especially in developing countries. This study aimed to evaluate the association between digital exclusion and cognitive function among elderly populations in developing countries. Using data from CHARLS (China Health and Retirement Longitudinal Study) from 2011 to 2020 and MHAS (Mexican Health & Aging Study) from 2012 to 2021, we defined digital exclusion as self-reported absence from the internet. Cognitive function was assessed through 5 tests: orientation, immediate verbal recall, delayed verbal recall, serial 7s, and figure recall. Cognitive function was assessed in 2 categories: worse cognition (a categorical variable that classifies cognition as either better or worse compared to the entire cohort population) and cognitive scores (a continuous variable representing raw cognitive scores across multiple follow-up waves). Logistic regression analyses and generalized estimating equation (GEE) analyses were used to examine the relationship between cognitive function and digital exclusion, adjusting for potential confounders, including demographics, lifestyle factors, history of chronic diseases, basic activities of daily living (BADL) disability, instrumental activities of daily living (IADL) disability, and basic cognitive abilities. After excluding participants with probable cognitive impairment at baseline and those who did not have a complete cognitive assessment in any given year (ie, all tests in the cognitive assessment must be completed in any follow-up wave), a total of 24,065 participants in CHARLS (n=11,505, 47.81%) and MHAS (n=12,560, 52.19%) were included. Of these, 96.78% (n=11,135) participants in CHARLS and 70.02% (n=8795) in MHAS experienced digital exclusion. Adjusted logistic regression analyses revealed that individuals with digital exclusion were more likely to exhibit worse cognitive performance in both CHARLS (odds ratio [OR] 2.04, 95% CI 1.42-2.99; P<.001) and MHAS (OR 1.40, 95% CI 1.26-1.55; P<.001). Gender and age did not significantly modify the relationship between digital exclusion and worse cognition (intervention P>.05). The fully adjusted mean differences in global cognitive scores between the 2 groups were 0.98 (95% CI 0.70-1.28; P<.001) in CHARLS and 0.50 (95% CI 0.40-0.59; P<.001) in MHAS. A substantial proportion of older adults, particularly in China, remain excluded from internet access. Our study examined longitudinal changes in cognitive scores and performed cross-sectional comparisons using Z-score standardization. The findings suggest that digital exclusion is linked to an increased risk of cognitive decline among older adults in developing countries. Promoting internet access may help mitigate this risk and support better cognitive health in these populations.

Immunosuppressive Drugs in Early Limited Cutaneous Systemic Sclerosis May Prevent Global Damage Accrual.

Organ damage in systemic sclerosis (SSc) in individual organs such as the lungs may be prevented by immunosuppressive drugs (IS). A new measure of global organ damage, the Scleroderma Clinical Trials Consortium Damage Index (SCTC-DI), has allowed us to investigate whether IS may reduce global organ damage accrual in early SSc. This was a retrospective study of patients with < 2 years disease duration in Canadian and Australian SSc cohorts. Patients with either limited cutaneous (lcSSc) or diffuse cutaneous (dcSSc) SSc were observed separately and divided into ever or never exposed to IS groups. The SCTC-DI was the outcome and inverse probability of treatment weighting (IPTW) was used to balance the study groups and to fit a marginal structural generalized estimating equation (GEE) model. In the lcSSc cohort, there were 210 subjects of which 34% were exposed to IS at some time. Exposure to IS was associated with lower damage scores. In the dcSSc cohort, there were 192 subjects of which 76% were exposed to IS at some time. Exposure to IS was not associated with damage scores. In this retrospective observational cohort study, using IPTW to adjust for confounders, we found a protective effect of the use of IS on damage accrual in lcSSc. We were unable to determine such an effect in dcSSc but unknown confounders may have been present and prospective studies of IS in dcSSc should include the SCTC-DI to determine the possible effect of IS on damage accrual.

Geessbin: an R package for analyzing small-sample binary data using modified generalized estimating equations with bias-adjusted covariance estimators.

The generalized estimating equation (GEE) method is widely used for analyzing longitudinal and clustered data. Although the GEE estimate for regression coefficients and sandwich covariance estimate are consistent regardless of the choice of covariance structure, they are generally biased for small sample sizes. Various researchers have proposed modified GEE methods and covariance estimators to handle small-sample bias. We briefly present bias-corrected and penalized GEE methods, along with 11 bias-adjusted covariance estimators. In addition, we focus on analyzing longitudinal or clustered data with binary outcomes using the logit link function and introduce package geessbin in R to implement conventional and modified GEE methods with bias-adjusted covariance estimators. Finally, we illustrate the implementation and detail a usage example of the package. The package is available from the Comprehensive R Archive Network (CRAN) at https://cran.r-project.org/web/packages/geessbin/index.html . The geessbin package provides three GEE estimates with numerous covariance estimates. It is useful for analyzing correlated data such as longitudinal and clustered data. Additionally, the geessbin is designed to be user-friendly, making it accessible to non-statisticians.

Stigma trajectories, disclosure, access to care, and peer-based supports among African, Caribbean, and Black im/migrant women living with HIV in Canada: findings from a cohort of women living with HIV in Metro Vancouver, Canada.

African, Caribbean, and Black im/migrant women experience a disproportionate burden of HIV relative to people born in Canada, yet there is scarce empirical evidence about the social and structural barriers that influence access to HIV care. The objectives of this study is to estimate associations between African, Caribbean, and Black background and stigma and non-consensual HIV disclosure outcomes, and to understand how experiences of stigma and im/migration trajectories shape access to HIV care and peer supports among African, Caribbean, and Black im/migrant women living with HIV in Canada. This mixed-methods analysis draws on interviewer-administered questionnaires and semi-structured interviews with self-identifying African, Caribbean, and Black women living with HIV in the community-based SHAWNA (Sexual Health and HIV/AIDS: Women's Longitudinal Needs Assessment) cohort. Bivariate and multivariable logistic regression using generalized estimating equations (GEE) were performed to estimate associations between African, Caribbean, and Black background and stigma and non-consensual HIV disclosure outcomes. Drawing on a social and structural determinants of health framework, qualitative analysis of interviews elucidated the interplay between migration trajectories, stigma, racialization, and HIV. Amongst our participants (n = 291), multivariable GEE analysis revealed that African, Caribbean, and Black participants (n = 15) had significantly higher odds of recently being outed without consent as living with HIV (AOR 2.34, 95% CI 0.98-5.57). Additionally, African, Caribbean, and Black participants had higher odds of recent verbal or physical abuse due to their HIV status (AOR 2.11, 95% CI 0.65-6.91). Reflecting on their im/migration trajectories, participants' narratives (n = 9) highlighted experiences of political violence and conflict, trauma, stigma, and discrimination associated with HIV in their place of origin and the racialization and stigmatization of HIV in Canada. Fear of disclosure without consent was linked to barriers of accessing care and peer-based supports. Our findings indicate that im/migration trajectories of African, Caribbean, and Black women living with HIV are critically related to accessing HIV care and supports in Canada and compound HIV stigma and discrimination. HIV disclosure without consent complicates access to care and social/peer support, underscoring the need for privacy, confidentiality, and the importance of building trust in the context of clinical encounters. The results of this study emphasize the critical need for culturally sensitive trauma-informed care models rooted in peer-based approaches.

Nutritional status and daily habits as determinants of hospitalization duration in ovarian cancer patients undergoing chemotherapy.

Adequate nutrition in a hospital setting is essential for achieving optimal health outcomes in oncology patients. This study specifically investigated the interrelationships between nutritional status, daily habits, and hospital length of stay (LOS) in ovarian cancer patients undergoing chemotherapy. A prospective longitudinal study was conducted from August 2019 to January 2022 in a tertiary hospital. Throughout the study, nutritional status, biochemical indicators, diet, and physical activity were meticulously recorded at different stages of chemotherapy: before chemotherapy (T0), the first course (T1), third course (T2), and fifth course (T3). To determine the factors influencing LOS, a generalized estimation equation (GEE) was employed. A total of 460 patients completed the follow-up period. The findings revealed a decline in nutritional risk among patients by 9.90% at T1, 17.62% at T2 and 18.26% at T3 (χ2 = 79.220, P < 0.001). The proportion of people receiving enteral nutrition showed an upward trend (χ2 = 15.202, P < 0.001). Notably, the proportion of patients adhering to a healthier diet increased by 40.44% by the study's conclusion, while the number of patients abstaining from physical activity or engaging in solely low-intensity activities decreased by 21.08%. Moreover, as the chemotherapy cycle progressed, daily activity steps exhibited an upward trajectory (F = 5.986, P < 0.001), while the LOS experienced a significant reduction (F = 21.298, P < 0.001). This study identified hypoproteinemia (protein level < 34g/L), a high nutritional risk (NRS 2002 score ≥ 3), a short duration of sleep (≤ 7h/day), and a lower daily activity level as risk factors for LOS. Receiving enteral nutrition support is a protective factor for LOS. Significant improvements in nutritional status, diet, and physical activity have been observed among ovarian cancer patients during their chemotherapy cycles. Reduced nutritional risks, implementation of nutritional support, good physical activity, and adequate sleep were associated with a shorter LOS.

The impact of job fitness on depressive symptoms in Korean middle-aged and older population: a longitudinal study

PurposeThis study aimed to determine the impact of job fitness on depression and depressive symptoms in Korean middle-aged and older population.MethodsWe collected data from the Korean Longitudinal Study of Aging (KLoSA), and performed a longitudinal analysis on 3,185 individuals with jobs at baseline. The dependent variable, depressive symptoms was measured by CES-D10 score, and the main variable of interest, job fitness was classified into nine groups according to job satisfaction and education level. To determine whether the estimate of depressive symptoms over the past week and depression changed over time, we applied the Generalized Estimating Equation (GEE) model.ResultsIn the fully adjusted model, the impact of job fitness on depression and depressive symptoms was statistically significant. Compared to those with a suitable job level and a medium educational level, those with a large gap between job and educational levels were more likely to develop depression and depressive symptoms. It was also found that satisfaction with job content was a crucial factor affecting depression in the middle-aged and older adults.ConclusionOur findings demonstrated that job fitness significantly influenced depression, even after accounting for the effect of job satisfaction caused by a mismatch in job-education fitness. Since work demands and responsibility are difficult to quantify or qualify, job-education fitness could serve as a valuable tool to predict the extent of depression deterioration in individuals.

Abstract Su304: The Effect of Time to DC Shock on Return of Spontaneous Circulation in Out-of-Hospital Cardiac Arrest with Recurrent Shockable Rhythm

Objective: The optimal timing for defibrillation attempts in out-of-hospital cardiac arrest (OHCA) patients with recurrent shockable rhythms [ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT)] is uncertain. This study examined the association between "time to DC shock" and the return of spontaneous circulation (ROSC) in OHCA patients with recurrent shockable rhythms. Methods: This was a retrospective analysis of data from the Salt Lake City Fire Department (SLCFD) from 2012 to 2023. Rhythm-filtering technology, used since 2012, enabled real-time and accurate interpretation of cardiac rhythms during CPR, with local protocols allowing early defibrillation for recurrent VF/ pulseless VT cases. Patients who experienced four or five episodes of shockable rhythms and received defibrillation were included. Generalized estimating equation (GEE) analysis was used to evaluate the association between time to shock preceding recurrent defibrillation and ROSC. Results: A total of 142 patients were included, with a mean age of 59.7 ± 15 years; 105 (73.9%) were male, 63 (44.4%) arrested in public locations, and 101 (71.1%) had witnessed arrests. Adjusted GEE analysis revealed that longer time to shock was associated with lower odds of achieving ROSC (OR: 0.81, 95% CI: 0.72–0.93, p = 0.005). Every one-minute delay in defibrillation is predicted to decrease the likelihood of achieving ROSC by 19%. Conclusion: In patients with recurrent shockable rhythms, every one-minute delay in delivering a shock was associated with a statistically significant 19% reduction in the chance of achieving ROSC. This finding highlights the importance of reducing the time to defibrillation in managing recurrent shockable rhythms and suggests reevaluating the current recommendation of two-minute intervals for rhythm check and shock delivery.

Internet Use Maintains Cognitive Function among middle- and old-aged Chinese: A Five-year Longitudinal Study.

Cognitive decline poses one of the greatest global challenges for health and social care, particularly in China, where the burden on the elderly population is most pronounced. Despite the rapid expansion of internet access, there is still limited understanding of the long-term cognitive impacts of internet usage among middle-aged and elderly individuals. This study aims to explore the association between internet usage and age-related cognitive decline among middle- and old-aged Chinese. To gain a more comprehensive understanding of the effects of internet usage, we also focused on assessing the impact of both the frequency of internet use and the types of internet devices on cognition. Moreover, we assessed the mediating role of internet usage on cognitive function for characteristics significantly linked to cognition in stratified analysis. We analyzed data based on 12,770 dementia-free participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study. We employed a fixed-effects model to assess the relationship between internet usage and cognitive decline, and further validated it using multiple linear regression, generalized estimating equations (GEE), propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting (OW). We further examined the varying effects of internet device type and frequency on cognitive function using fixed-effects models and Spearman's rank correlation. The Karlson-Holm-Breen (KHB) method was used to estimate the mediating role of internet usage in the urban-rural cognitive gap. Participants using the internet (n=1,005) were younger, more likely to be male, more educated, married, retired, living in an urban area, and had higher cognitive assessment scores compared with non-users (n=11,765). After adjusting for demographic and health-related risk factors, there was a positive correlation between internet use and cognitive function (β=0.551, 95% CI 0.391 to 0.710). Over the follow-up period, persistent internet users had a markedly lower 5-year incidence of neurodegenerative diseases at 2.2% (15/671) compared with non-users at 5.3% (379/7,099; P<.001). The negative impact of aging (> 50) on cognitive function was consistently less pronounced among internet users compared to non-users. Furthermore, increased frequency of internet usage was associated with greater cognitive benefits for middle-aged and elderly individuals (rs = 0.378, P<.001). Among digital devices used for internet access, cellphones (β=0.398, 95% CI 0.283 to 0.495) seem to have a higher level of cognitive protection compared to computers (β=0.147, 95% CI 0.091 to 0.204). The urban-rural disparity in cognitive function was partially attributed to the disparity in internet use (34.2% of the total effects, P<0.001). This study reveals that the use of internet by individuals aged 45 years and older is associated with a reduced risk of cognitive decline. Internet usagehas the potential to be a viable, cost-effective, non-pharmacological intervention forcognitive decline among middle-aged and elderly individuals.

Impact of baseline dietary quality on the efficacy of a dietitian-guided weight reduction program.

This pre-post intervention study aimed to assess the relationship between baseline dietary quality and the efficacy of a dietitian-guided weight reduction program, which has not been thoroughly documented to date. Ninety-two consecutive obese or overweight patients visiting a tertiary center clinic for weight reduction were enrolled in this study. Participants received a dietitian-guided weight reduction education program aimed at reducing daily caloric intake by 500kcal and improving adherence to the Mediterranean diet for 3 months. Baseline dietary quality was assessed using the 14-item Taiwanese Mediterranean Diet Adherence Screener (T-MEDAS), where a higher T-MEDAS score reflects greater adherence to the Mediterranean diet. Additional covariates, including dietary behaviors, lifestyle factors, and comorbidities were also recorded. The primary outcome was the percentage of weight reduction at 3 months, analyzed using restricted cubic spline models and generalized estimating equations (GEE) to account for the correlation between weight change and the baseline T-MEDAS scores. Thirty-nine participants were excluded due to major illnesses, use of anti-obesity medications, or loss to follow-up. Among the remaining 53 participants (mean age 41.2 ± 12.8 years, 56.6% female), the average weight reduction was 3.9 ± 3.3% from a baseline weight of 98.5 ± 12.8kg. Participants who did not achieve a weight reduction of more than 5% had higher baseline T-MEDAS scores compared to those who did (5.4 ± 1.7 vs. 4.1 ± 1.8, p = 0.026). A restricted cubic spline model, adjusted for covariates including age, gender, diabetes mellitus (DM), dyslipidemia, and smoking, revealed a significant inverse relationship between higher baseline T-MEDAS scores and weight loss. After controlling for various confounders, GEE analysis demonstrated that higher baseline T-MEDAS scores were significantly associated with less weight loss (beta: -4.1, 95% CI: -5.6 to -2.6, p < 0.001). Higher baseline dietary quality was associated with reduced effectiveness of a dietitian-guided weight reduction program. This suggests that additional strategies may be required to improve the success of weight loss interventions in individuals with higher baseline dietary quality.

Characteristics and influencing factors of immunological non-responders in HIV-1-infected patients receiving antiretroviral therapy: a cross-sectional study in Guangxi.

The prevalence of AIDS and mortality rates among HIV-infected individuals in Guangxi remain relatively high, potentially due to impaired CD4 + cell recovery. This study aims to identify factors hindering CD4 + cell recovery in people living with HIV. We conducted a retrospective study on people living with HIV in Guangxi, China, with data collection extending to the end of 2023. CD4 + T cells were categorized into "immunological responders" and "non-responders" based on CD4 + cell recovery after treatment. Multivariate logistic regression was used to analyze factors associated with the development of immunological non-responders. Recovery of CD4 + T lymphocytes was assessed using the Generalized Additive Mixed Model (GAMM) and Generalized Estimating Equations (GEE). Additionally, multivariate Cox regression identified factors influencing survival rates. Our findings indicated a 52.44% incidence of immunological non-responders after two years of treatment. Factors such as age, sex, education, occupation, infection route, pre-treatment CD4 + T cell count, HIV subtype, and treatment regimen were linked to immunological non-response. Specifically, male gender, education up to high school, farming occupation, heterosexual transmission, CRF01_AE subtype, pre-treatment CD4 + T cell count < 200/µL, and the 3TC + EFV + TDF regimen were identified as significant risk factors. Statistically significant differences in CD4 + T lymphocyte recovery rates were observed among different HIV subtypes (P < 0.05). Beyond age, sex, ethnicity, occupation, subtype, and treatment regimen, being an immunological non-responder was found to be a risk factor for both mortality and accelerated disease progression. The study highlights the complexity of factors affecting CD4 + cell recovery post-HIV treatment in Guangxi and underscores the need for vigilant clinical monitoring of people living with HIV, particularly those with low pre-treatment CD4 + T cell levels.

Using Multilevel Models and Generalized Estimating Equation Models to Account for Clustering in Neurology Clinical Research.

In clinical and health services research, clustered data (also known as data with a multilevel or hierarchical structure) are frequently encountered. For example, patients may be clustered or nested within hospitals. Understanding when data have a multilevel structure is important because clustering of individuals can induce a homogeneity in outcomes within clusters, so that, even after adjusting for measured covariates, outcomes for 2 individuals in the same cluster are more likely to be similar than outcomes for 2 individuals from different clusters. Using conventional statistical regression models to analyze clustered data can result in incorrect conclusions being drawn. In particular, estimated CIs may be artificially narrow, and significance levels may be artificially low. As a result, one may conclude that there is a statistically significant association when there is none. To avoid this problem, investigators should ensure that their analyses use techniques that account for clustering of data. Generalized linear models estimated using generalized estimating equation (GEE) methods and multilevel regression models (also known as hierarchical regression models, mixed-effects models, or random-effects models) are two such techniques. We provide an introduction to clustered or multilevel data and describe how GEE models or multilevel models can be used for the analysis of multilevel data.

Handling missing data in longitudinal clinical trials: three examples from the pediatric psychology literature.

Researchers by default tend to choose complex models when analyzing nonindependent response variable data, this may be particularly applicable in the analysis of longitudinal trial data, possibly due to the ability of such models to easily address missing data by default. Both maximum-likelihood (ML) estimation and multiple imputation (MI) are well-known to be acceptable methods for handling missing data, but much of the recently published quantitative literature has addressed questions regarding the research designs and circumstances under which one should be chosen over the other. The purpose of this article is threefold. First, to clearly define the assumptions underlying three common longitudinal trial data analysis models for continuous dependent variable data: repeated measures analysis of covariance (RM-ANCOVA), generalized estimating equation (GEE), and a longitudinal linear mixed model (LLMM). Second, to clarify when ML or MI should be chosen, and to introduce researchers to an easy-to-use, empirically well-validated, and freely available missing data multiple imputation program: BLIMP. Third, to show how missing longitudinal trial data can be handled in the three data analysis models using three popular statistical analysis software packages (SPSS, Stata, and R) while keeping the published quantitative research in mind.

Oral cyclophosphamide monotherapy in advanced resistant ocular cicatricial pemphigoid

Abstract: PURPOSE: The purpose of the study was to study the efficacy of oral cyclophosphamide monotherapy in advanced resistant ocular cicatricial pemphigoid (OCP). MATERIALS AND METHODS: This retrospective case series examines patients diagnosed with advanced resistant OCP at a uveitis tertiary care center who were treated with oral cyclophosphamide therapy. RESULTS: Seventeen patients were included in this study. The average age of the participants was 74.3 ± 10.3 years, ranging from 60 to 99 years. The gender distribution was 8 females to 9 males. Oral cyclophosphamide-induced remission in 7 patients (41.1%) and was prematurely discontinued in 10 patients (58.9%), with 7 (63.7%) citing ineffectiveness and 3 (36.3%) experiencing side effects as reasons for discontinuation. The average therapy dose of cyclophosphamide administered was 116.1 ± 47.5 mg. The average duration required for the induction of remission was 150 ± 128 days. The overall therapy duration averaged 306 ± 189 days. Conducting univariate logistic regression with generalized estimating equations (GEEs) on variables did not reveal statistically significant differences between the two groups (responsive and nonresponsive to oral cyclophosphamide therapy), except for the maximum dose of oral cyclophosphamide therapy (P = 0.007). CONCLUSION: The prognosis of advanced OCP in patients is unlikely to be altered by the stepladder approach and step-up strategy. While oral cyclophosphamide can be efficacious for remission induction in resistant and aggressive OCP cases, a step-down strategy employing less potent agents with safer side effect profiles should be contemplated for subsequent treatment.

The effectiveness of a problem-solving intervention with workplace involvement on self-reported sick leave, psychological symptoms and work ability: a cluster randomised clinical trial.

Problem-solving interventions with workplace involvement (PSI-WPI) have been shown to reduce sick leave and increase return to work in an occupational health services context. However, many employees struggle with reduced work functioning, anxiety-, and depressive symptoms up to 12months after a sick leave episode, and it is unclear if the intervention affects outcomes other than sick leave. The aim of this study is to investigate if a PSI-WPI added to care as usual (CAU) is superior to CAU with respect to self-reported sick leave, psychological symptoms, work ability, work performance, and health after RTW when provided in primary care. Employed individuals aged 18-59years on sick leave (2 to 12weeks) diagnosed by a physician at a primary care center with mild to moderate depression, anxiety, or adjustment disorder were enrolled in a two-armed cluster-randomised trial evaluating the effectiveness of a PSI-WPI. Multiple outcomes were recorded at baseline, six months, 12months, and every fourth week during the study period. Outcomes were categorised into psychological symptoms, health, work ability, work performance, and self-reported sick leave. Data were analysed using MANOVA, GEE (Generalized Estimating Equations), and cox regression. One hundred ninety-nine individuals responded to the invitation to participate; one participant withdrew, one was excluded as the employment ended, nine did not answer the baseline survey, and three were removed from the analysis due to missing data. The analysis included 81 subjects who received the intervention and 104 subjects who received the control. Baseline characteristics were similar across both groups. No differences between the groups were found among either variables except one. There was a significant difference between the groups in self-rated health (EQ5D) in favour of the CAU group from baseline to six-month follow-up, with a mean difference of -8.44 (-14.84, -2.04). A problem-solving intervention with workplace involvement added to CAU did not result in statistically significant reductions in outcomes. Further research is needed to understand why problem-solving interventions appear to have an effect on sick leave in an occupational health services context and not in a primary care context. NCT3346395, registration date 2017-11-17.

Norwegian and Swedish value sets for the EORTC QLU-C10D utility instrument.

This study aimed to develop utility weights for the European Organization for Research and Treatment of Cancer (EORTC) QLU-C10D, a cancer-specific utility instrument, tailored to the Norwegian and Swedish populations. The utility weights are intended for use in the specific welfare contexts of Norway and Sweden to support more precise healthcare decision-making in cancer treatment and care. This cross-sectional study included 1019 Norwegian and 1048 Swedish participants representative in age and gender of the two general populations. Participants completed a discrete choice experiment involving 960 choice sets, each consisting of two EORTC QLU-C10D health states described by the instrument's domains and the duration of each state. Utility weights were calculated using generalized estimation equation models, and non-monotonic levels were merged to ensure consistent valuation. In the Norwegian participants, the largest utility decrements were seen for the domain of physical functioning (decrement of -0.263 for highest level "very much"), followed by pain (decrement -0.205 for level "very much") and role functioning (-0.139). Among the cancer-specific domains, nausea had the largest utility decrement (-0.124). In the Swedish participants, the largest utility decrements were also observed for physical functioning (-0.207 for the response "very much"), followed by pain (-0.139), role functioning (-0.133), and nausea (-0.119). Emotional functioning also exhibited a sizable utility decrement (-0.115). This study provides the first set of utility weights for the EORTC QLU-C10D specific to Norway and Sweden, reflecting the unique health preferences of these populations. The generated utility decrements can inform cost-utility analyses and optimize resource allocation in cancer care within the Norwegian and Swedish healthcare systems.

Gadoxetic acid-enhanced MRI for the detection of liver metastases from melanoma.

We aimed to assess imaging findings and detection sensitivity for melanoma liver metastases on gadoxetic acid-enhanced magnetic resonance imaging (MRI). This retrospective study included patients with melanoma liver metastasis who underwent gadoxetic acid-enhanced MRI. Two abdominal radiologists independently evaluated signal characteristics of liver metastases on morphologic imaging (precontrast T1- and T2-weighted imaging), diffusion-weighted imaging (DWI), dynamic imaging, and hepatobiliary phase (HBP). Imaging findings were compared according to detection on HBP and the primary site of the melanoma using logistic regression with the generalized estimating equation (GEE). Detection sensitivity for metastases was compared among different MR imaging sets using logistic regression with GEE. A total of 67 patients with 254 liver metastases were included (44 women; mean age ± standard deviation, 65.6 ± 13.0 years). On HBP, 76.0% of metastases were detected, and 55.5% (141/254) showed hypointensity. Most of the metastases that were not detected on HBP originated from ocular melanomas (98.4%, 60/61), ≤1 cm (90.2%, 55/61) and showed T1 hyperintensity (98.4%, 60/61). Metastases from non-ocular melanomas more frequently showed T1 hypointensity, T2 hyperintensity, diffusion restriction, arterial enhancement, and HBP hypointensity than those from ocular melanomas (Ps ≤ 0.019). The detection sensitivity of HBP (76.0%) was significantly higher than DWI (65.7%, P = 0.006), but lower than morphologic imaging (98.8%, P < 0.001) and dynamic imaging (97.6%, P < 0.001). The detection sensitivity of HBP for melanoma liver metastasis was 76.0%, which was lower than that of morphologic or dynamic imaging. HBP of gadoxetic acid-enhanced MRI has little advantage in detecting melanoma liver metastases.

Geographical variation in osteoporosis in Australian women: a longitudinal analysis over 23years.

To determine whether the prevalence of osteoporosis, fractures, and dual-X-ray absorptiometry (DXA) differs between Australian women living in rural compared with urban areas. The Australian Longitudinal Study on Women's Health, a prospective longitudinal study of Australian women, includes a cohort of women born 1946-1951, surveyed nine times from 1996-2019. Data from administrative health records were linked to survey data. Geographic area was classified as major city, inner regional, outer regional, or remote. Generalised estimating equations (GEE) explored outcomes of osteoporosis, fracture, and DXA rates. Univariable and multivariable regression were performed and bootstrapping with 100 repetitions at 95% sampling of the original dataset to ensure robust results. A total of 13,712 women were included: 5000 (36.5%) living in major cities, 5214 (38.0%) inner regional, 2798 (20.41%) outer regional, and 700 (5.1%) remote areas. Baseline age, 47.6 (1.46) years (mean (SD)), was similar; but education, marital status, country of birth, smoking, BMI, and comorbidities varied between areas. Over 23years, 2956 (21.6%) were diagnosed with osteoporosis, 3185 (23.2%) had an incident fracture, and 8151 (59.4%) had a DXA. On univariable analysis, women living outside major cities had lower risk of osteoporosis (inner regional OR 0.92; 95% CI 0.84, 0.99; outer regional 0.70; 0.63, 0.79; remote 0.43; 0.34, 0.53), and lower risk of fractures (inner regional area OR 0.92, 95% CI 0.84, 0.99; outer regional 0.81; 0.73, 0.90; remote 0.54; 0.42, 0.67), than women living in major cities. These differences were no longer significant on multivariable analysis, suggesting differences might be related to the distribution of risk factors. Women living in inner regional and outer regional areas were significantly less likely to have a DXA, than those living in a major city (OR 0.75, 95% CI 0.70, 0.81; OR 0.72; 95% CI 0.64, 0.77, respectively), and this remained significant on multivariable analysis. Osteoporosis or fracture affected one-third of older Australian women, and women living outside major cities had lower rates of osteoporosis, fractures, and DXA completion.

The relationship between walking speed, step parameters, and margins of stability in individuals after stroke

BackgroundIndividuals after stroke walk with different step parameters and consequently with different margins of stability compared to able-bodied peers. These differences might be a side effect of lower preferred walking speeds or primary limitations in regulating step parameters and margins of stability after stroke. MethodsTwenty-eight individuals after stroke (separated into more impaired and less impaired based on speed) and fourteen able-bodied peers completed five walking trials on an instrumented treadmill at 70 %, 85 %, 100 %, 115 %, and 130 % of their preferred speed. Center of pressure data were used to calculate stride frequency, stride length, step width and margins of stability in mediolateral and anteroposterior direction. Generalized estimation equations were used to analyze the (interaction) effects of group, speed, and most versus least affected leg on these parameters. FindingsWhen controlled for speed, all individuals after stroke walked with higher stride frequencies (P < 0.001) and shorter stride lengths (P < 0.001) than able-bodied peers. Less impaired individuals walked with larger step widths than able-bodied peers (P < 0.001). The interaction effect of group and speed suggested that individuals after stroke showed higher increases in stride length with increasing speed than able-bodied peers. When controlled for speed, mediolateral margins of stability were larger in less impaired individuals compared to able-bodied peers, but otherwise, margins of stability did not differ between groups. Only minor differences between the most and least affected leg were observed. InterpretationDifferences in step parameters between individuals after stroke and able-bodied peers seem independent of walking speed and function to enhance gait stability.