Category: Nevin Manimala

Br J Cancer. 2023 Nov 11. doi: 10.1038/s41416-023-02492-8. Online ahead of print.

ABSTRACT

BACKGROUND: Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant PC (nmCRPC) in the Phase 3 randomised TITAN and SPARTAN studies, respectively, and maintained health-related quality of life (HRQoL). Apalutamide treatment effect by patient age requires assessment.

METHODS: Post-hoc analysis assessed patients receiving 240 mg/day apalutamide (525 TITAN and 806 SPARTAN) or placebo (527 TITAN and 401 SPARTAN) with ongoing ADT, stratified by age groups. Prostate-specific antigen declines, radiographic progression-free survival, metastasis-free survival, overall survival (OS), HRQoL and safety were assessed using descriptive statistics, Kaplan-Meier method, Cox proportional-hazards model and mixed-effects model for repeated measures.

RESULTS: Hazard ratios (95% confidence intervals) generally favoured apalutamide plus ADT versus ADT alone across all endpoints regardless of age; e.g., OS values were 0.57 (0.40-0.80), 0.70 (0.54-0.91) and 0.74 (0.40-1.39) (TITAN) and 0.39 (0.19-0.78), 0.89 (0.69-1.16) and 0.81 (0.58-1.15) (SPARTAN) in patients aged <65, 65-79 and ≥80 years. Regardless of age, apalutamide also maintained HRQoL and was tolerated well with a potential trend in rates of adverse events increasing with age. Limitations include post-hoc nature and variability in sample size of age groups.

CONCLUSIONS: Apalutamide plus ADT was an effective and well-tolerated option maintaining HRQoL in patients with mCSPC and nmCRPC regardless of age.

CLINICAL TRIAL REGISTRATION: TITAN (NCT02489318); SPARTAN (NCT01946204).

PMID:37951974 | DOI:10.1038/s41416-023-02492-8

Nat Commun. 2023 Nov 11;14(1):7311. doi: 10.1038/s41467-023-42868-1.

ABSTRACT

Human social interactions tend to vary in intensity over time, whether they are in person or online. Variable rates of interaction in structured populations can be described by networks with the time-varying activity of links and nodes. One of the key statistics to summarize temporal patterns is the inter-event time, namely the duration between successive pairwise interactions. Empirical studies have found inter-event time distributions that are heavy-tailed, for both physical and digital interactions. But it is difficult to construct theoretical models of time-varying activity on a network that reproduce the burstiness seen in empirical data. Here we develop a spanning-tree method to construct temporal networks and activity patterns with bursty behavior. Our method ensures any desired target inter-event time distributions for individual nodes and links, provided the distributions fulfill a consistency condition, regardless of whether the underlying topology is static or time-varying. We show that this model can reproduce burstiness found in empirical datasets, and so it may serve as a basis for studying dynamic processes in real-world bursty interactions.

PMID:37951967 | DOI:10.1038/s41467-023-42868-1

Lipids Health Dis. 2023 Nov 11;22(1):193. doi: 10.1186/s12944-023-01958-1.

ABSTRACT

BACKGROUND: The association between triglyceride-glucose (TyG) index and poor prognosis remains controversial. Whether renal function status affects the ability of the TyG index to predict poor prognosis has not yet been elucidated and merits further studies.

METHODS: This retrospective cohort study included 22,031 participants from communities in the U.S. By juxtaposing the TyG categories with the estimated glomerular filtration rate (eGFR, either < 60 mL/min/1.73m² or ≥ 60 mL/min/1.73m²), participants were categorized into four distinct groups: (1) TyG_L/eGFR_H; (2) TyG_H/eGFR_H; (3) TyG_L/eGFR_L; and (4) TyG_H/eGFR_L. The endpoint was the all-cause mortality rate. Standard Kaplan-Meier plots were constructed and multifactor Cox regression analyses were carried out and restricted cubic spline regression analysis was utilized to assess the association between death and the TyG index for different renal function statuses.

RESULTS: No statistical differences were found in the TyG groups in participants with normal renal function after adjustment for all covariates (P = 0.070). However, in the high TyG index group with renal insufficiency, the risk of all-cause mortality rates was reduced by 18%. (HR, 0.82; CI, 0.69-0.98). The TyG index (high vs. low) and renal function (eGFR < 60 vs. eGFR ≥ 60) had statistically significant interactions with death (P < 0.001). When all covariates were adjusted, the risk of mortality for the TyG_L combined with eGFR_L group was 56% higher than that for the TyG_L combined with eGFR_H group (HR, 1.56; CI, 1.33-1.82). In the renal insufficiency population, a nonlinear relationship was observed between mortality and the TyG index, albeit with a differing pattern (P for nonlinearity < 0.001).

CONCLUSIONS: While it has been known that TyG index was a prognosis marker of CVD, this research highlights that higher TyG index was associated with higher all-cause mortality rates for all participants. Furthermore, renal function status significantly moderates the effect of the TyG index on all-cause mortality in community-dwelling adults.

PMID:37951945 | DOI:10.1186/s12944-023-01958-1

BMC Med Genomics. 2023 Nov 11;16(1):284. doi: 10.1186/s12920-023-01710-9.

ABSTRACT

Deep vein thrombosis (DVT) is the formation of a blood clot in a deep vein. DVT can lead to a venous thromboembolism (VTE), the combined term for DVT and pulmonary embolism, a leading cause of death and disability worldwide. Despite the prevalence and associated morbidity of DVT, the underlying causes are not well understood. Our aim was to leverage publicly available genetic summary association statistics to identify causal risk factors for DVT. We conducted a Mendelian randomization phenome-wide association study (MR-PheWAS) using genetic summary association statistics for 973 exposures and DVT (6,767 cases and 330,392 controls in UK Biobank). There was evidence for a causal effect of 57 exposures on DVT risk, including previously reported risk factors (e.g. body mass index-BMI and height) and novel risk factors (e.g. hyperthyroidism and varicose veins). As the majority of identified risk factors were adiposity-related, we explored the molecular link with DVT by undertaking a two-sample MR mediation analysis of BMI-associated circulating proteins on DVT risk. Our results indicate that circulating neurogenic locus notch homolog protein 1 (NOTCH1), inhibin beta C chain (INHBC) and plasminogen activator inhibitor 1 (PAI-1) influence DVT risk, with PAI-1 mediating the BMI-DVT relationship. Using a phenome-wide approach, we provide putative causal evidence that hyperthyroidism, varicose veins and BMI enhance the risk of DVT. Furthermore, the circulating protein PAI-1 has a causal role in DVT aetiology and is involved in mediating the BMI-DVT relationship.

PMID:37951941 | DOI:10.1186/s12920-023-01710-9

Alzheimers Res Ther. 2023 Nov 11;15(1):198. doi: 10.1186/s13195-023-01341-3.

ABSTRACT

BACKGROUND: Subjective cognitive complaints (SCC) have been mostly studied in the context of Alzheimer’s disease in memory clinic settings. The potential of combining SCC with genetic information and blood biomarkers of neurodegenerative diseases for risk assessment of dementia and depression in the absence of dementia among community-dwelling older adults has so far not been explored.

METHODS: Data were based on a population-based cohort of 6357 participants with a 17-year follow-up (ESTHER study) and a clinic-based cohort of 422 patients. Participants of both cohorts were grouped according to the diagnosis of dementia (yes/no) and the diagnosis of depression in the absence of dementia (yes/no). Participants without dementia included both cognitively unimpaired participants and cognitively impaired participants. Genetic information (APOE ε4 genotype) and blood-based biomarkers of neurodegenerative diseases (glial fibrillary acidic protein; GFAP, neurofilament light chain; NfL, phosphorylated tau181; p-tau181) were available in the ESTHER study and were determined with Simoa Technology in a nested case-control design. Logistic regression models adjusted for relevant confounders were run for the outcomes of all-cause dementia and depression in the absence of dementia.

RESULTS: The results showed that persistent SCC were associated both with increased risk of all-cause dementia and of depression without dementia, independently of the diagnostic setting. However, the results for the ESTHER study also showed that the combination of subjective complaints with APOE ε4 and with increased GFAP concentrations in the blood yielded a substantially increased risk of all-cause dementia (OR 5.35; 95%CI 3.25-8.81, p-value < 0.0001 and OR 7.52; 95%CI 2.79-20.29, p-value < 0.0001, respectively) but not of depression. Associations of NfL and p-tau181 with risk of all-cause dementia and depression were not statistically significant, either alone or in combination with SCC, but increased concentrations of p-tau181 seemed to be associated with an increased risk for depression.

CONCLUSION: In community and clinical settings, SCC predict both dementia and depression in the absence of dementia. The addition of GFAP could differentiate between the risk of all-cause dementia and the risk of depression among individuals without dementia.

PMID:37951931 | DOI:10.1186/s13195-023-01341-3

BMC Health Serv Res. 2023 Nov 11;23(1):1240. doi: 10.1186/s12913-023-10302-3.

ABSTRACT

BACKGROUND: Many Nigerians pay out-of-pocket for their health care, and some hospitals have started utilising e-payment systems to increase transactional efficiency. The study investigated the type and usage of e-payment platforms in public hospitals and the factors that may influence the managerial staff’s disposition towards using the e-payment system.

METHODS: We conducted a cross-sectional survey of 300 managerial staff within the four public tertiary hospitals in Enugu, Nigeria, through proportionate quota sampling. The survey obtained participants’ demographic characteristics, types of e-payment platforms, managerial staff’s technophobia, perception of credibility, and disposition towards e-payment. Data were analysed using descriptive statistics, Spearman correlation, and hierarchical linear regression.

RESULTS: The majority of the respondents (n = 278, 92.7% completion rate) aged 43.4 ± 7.6 years were females (59.0%) with a bachelor’s degree (54.7%). Their disposition (80.0%±17.9%), perceptions of the usefulness (85.7 ± 13.9%), and user-friendliness (80.5 ± 18.1%) of e-payment in the hospital were positive, credibility (72.6 ± 20.1%) and technophobia (68.0 ± 20.7%) were moderate. There was a negative correlation between technophobia and disposition toward the use of e-payment (ρ = -0.50, P < 0.001). Significant multivariate predictors of managerial disposition towards e-payment were; being a woman (β = 0.12, P = 0.033), married (β = 0.18, P = 0.003), positive perception of usefulness (β = 0.14, P = 0.025), and credibility (β = 0.15, P = 0.032).

CONCLUSION: Most participants had a positive disposition towards e-payment in public hospitals. However, managers with technophobia, a negative perception of e-payment usefulness, and credibility had a lesser disposition to its use. To ensure the universal implementation of e-payment in Nigerian hospitals, the service providers should make the e-payment platforms more secure and user-friendly to health services consumers and providers.

PMID:37951924 | DOI:10.1186/s12913-023-10302-3

AIDS Res Ther. 2023 Nov 11;20(1):79. doi: 10.1186/s12981-023-00575-3.

ABSTRACT

BACKGROUND: People with human immunodeficiency virus have an increased risk of developing AIDS-defining malignancies including Burkitt lymphoma. Survival outcomes in HIV-associated Burkitt lymphoma remain worse than non-HIV-associated Burkitt lymphoma, despite widespread implementation of antiretroviral therapy. We aimed to determine the association between HIV status and risk for 30-day and 90-day readmission in the US after index hospitalization for Burkitt lymphoma.

METHODS: Data were abstracted from the 2010-2020 Nationwide Readmissions Database; hospitalizations included patients with a primary BL diagnosis and were stratified by comorbid HIV. The primary outcome was all-cause readmission (30-day and 90-day). Secondary outcomes were in-hospital mortality, length of stay (LOS), and hospital cost. Between-HIV differences were evaluated via logistic and log-normal regression; multivariable models adjusted for comorbid kidney disease, hypertension, fluid and electrolyte disorders, and sepsis.

RESULTS: Overall, there were 8,453 hospitalizations for BL and 6.0% carried an HIV diagnosis. Of BL hospitalizations, 68.4% were readmitted within 30-days post index BL hospitalization and 6.8% carried a HIV diagnosis. HIV-associated BL was associated with 43% higher adjusted odds of 30-day readmission (aOR 95% CI: 4% higher to 97% higher, p = 0.026). For 90-day readmission, 76.0% of BL patients were readmitted and 7.0% carried a HIV diagnosis. HIV-associated BL was not statistically associated with all-cause 90-day readmission (aOR 1.46, aOR 95% CI: 0% higher to 115% higher, p = 0.053).

CONCLUSIONS: HIV-positive status is associated with an increased risk for 30-day readmission after index hospitalization for Burkitt lymphoma.

PMID:37951907 | DOI:10.1186/s12981-023-00575-3

BMC Oral Health. 2023 Nov 11;23(1):853. doi: 10.1186/s12903-023-03605-8.

ABSTRACT

BACKGROUND: An increasing number of patients with advanced stages of periodontitis are seeking for treatment options. The study aimed to determine interest in orthodontic treatment (OT) and its association with oral health status and knowledge about the disease in adult subjects with stage III-IV periodontitis.

METHODS: 96 subjects ≥ 30 years, with stage III-IV periodontitis agreed to fill in a questionnaire and undergo a comprehensive periodontal-orthodontic examination. The questionnaire included 44 questions: demographic, dental, health related habits, self-perceived overall and oral health, knowledge of periodontitis, and attitude toward OT. The statistical analysis was performed using a paired-sample T-test, Receiver Operating Characteristic (ROC) and binary logistic regression analysis (LRA).

RESULTS: Stage IV periodontitis was observed in 32.3% of subjects and Class II malocclusion was most prevalent (53.1%). More than half of subjects were interested in OT. Oral health, knowledge about periodontitis and age were significant predictors for interest in OT.

CONCLUSIONS: Knowledge spread about OT possibilities in advanced stages of periodontitis is very important both for the dental community and older subjects to save natural dentition.

PMID:37951899 | DOI:10.1186/s12903-023-03605-8

BMC Med Res Methodol. 2023 Nov 11;23(1):266. doi: 10.1186/s12874-023-02099-w.

ABSTRACT

BACKGROUND: There is growing interest in whether linked administrative data have the potential to aid analyses subject to missing data in cohort studies.

METHODS: Using linked 1958 National Child Development Study (NCDS; British cohort born in 1958, n = 18,558) and Hospital Episode Statistics (HES) data, we applied a LASSO variable selection approach to identify HES variables which are predictive of non-response at the age 55 sweep of NCDS. We then included these variables as auxiliary variables in multiple imputation (MI) analyses to explore the extent to which they helped restore sample representativeness of the respondents together with the imputed non-respondents in terms of early life variables (father’s social class at birth, cognitive ability at age 7) and relative to external population benchmarks (educational qualifications and marital status at age 55).

RESULTS: We identified 10 HES variables that were predictive of non-response at age 55 in NCDS. For example, cohort members who had been treated for adult mental illness had more than 70% greater odds of bring non-respondents (odds ratio 1.73; 95% confidence interval 1.17, 2.51). Inclusion of these HES variables in MI analyses only helped to restore sample representativeness to a limited extent. Furthermore, there was essentially no additional gain in sample representativeness relative to analyses using only previously identified survey predictors of non-response (i.e. NCDS rather than HES variables).

CONCLUSIONS: Inclusion of HES variables only aided missing data handling in NCDS to a limited extent. However, these findings may not generalise to other analyses, cohorts or linked administrative datasets. This work provides a demonstration of the use of linked administrative data for the handling of missing cohort data which we hope will act as template for others.

PMID:37951893 | DOI:10.1186/s12874-023-02099-w

BMC Pulm Med. 2023 Nov 11;23(1):439. doi: 10.1186/s12890-023-02627-w.

ABSTRACT

BACKGROUND: Our aims were to describe respiratory sequelae up to 12 months after discharge in COVID-19 patients with severe pneumonia requiring non-invasive respiratory support therapies.

METHODS: This study was undertaken at University Hospital Doctor Josep Trueta (Girona, Spain) between March 2020 and June 2020. Three months after discharge, we evaluated their dyspnoea and performed Saint George’s respiratory questionnaire, pulmonary function tests, blood test, 6-min walking test, and a high-resolution CT (HRCT). At the six and 12-month follow-up, we repeated all tests except for pulmonary function, 6-min walking test, and HRCT, which were performed only if abnormal findings had been previously detected.

RESULTS: Out of the 94 patients recruited, 73% were male, the median age was 62.9 years old, and most were non-smokers (58%). When comparing data three and 12 months after discharge, the percentage of patients presenting dyspnoea ≥ 2 decreased (19% vs 7%), the quality-of-life total score improved (22.8% vs 18.9%; p = 0.019), there were less abnormal results in the pulmonary function tests (47% vs 23%), the 6-min walking test distance was enhanced (368.3 m vs 390.7 m, p = 0.020), ground glass opacities findings waned (51.6% vs 11.5%), and traction bronchiectasis increased (5.6% vs 15.9%). Only age showed significant differences between patients with and without pulmonary fibrotic-like changes.

CONCLUSION: Most patients improved their clinical condition, pulmonary function, exercise capacity and quality of life one year after discharge. Nonetheless, pulmonary fibrotic-like changes were observed during the follow-ups.

PMID:37951891 | DOI:10.1186/s12890-023-02627-w