Nevin Manimala

Gerontol Geriatr Educ. 2023 Aug 30:1-17. doi: 10.1080/02701960.2023.2252368. Online ahead of print.

ABSTRACT

Healthy and active aging and age-friendly society frameworks attempt to address the well-documented challenges and opportunities of population aging. To meet the needs of an increasingly older society, there is a demand for professionals with appropriate age-related knowledge and skills. To this end, a master’s in active aging is in development. This study reports on the consultation with prospective students, employers, older people and academics on the knowledge areas to be included in the course. An anonymous online survey gathered data from stakeholders in Ireland, Slovenia, Austria, Portugal, Finland, and Greece. Participants ranked the importance of 14 broad knowledge areas and linked topics. The influence of participant characteristics on decisions was examined using multivariate regression modeling. Across all stakeholder groups (total sample N = 757), health promotion was most often deemed very important (80%), followed by psychology (73%), and social inclusion and engagement (71%). Potential students from healthcare backgrounds were more interested than others in aging physiology, social aspects, and the physical environment. More western-located European countries overall showed more enthusiasm for the topics presented, additional to regional variations between topics. This learning needs analysis provides multi-stakeholder insights into priorities regarding learning in healthy and active aging and age-friendly society.

PMID:37647110 | DOI:10.1080/02701960.2023.2252368

JAMA Netw Open. 2023 Aug 1;6(8):e2331295. doi: 10.1001/jamanetworkopen.2023.31295.

ABSTRACT

IMPORTANCE: Racial disparities in breast cancer (BC) survival arise from multilevel causes, which may exert influence at different stages of BC progression. Clarifying the importance of genetic and social factors could help prioritize interventions.

OBJECTIVE: To jointly examine associations between African genetic ancestry, social environment, and mortality from any cause and BC in Black BC survivors.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study enrolled self-identified Black women aged 20 to 75 years with histologically confirmed BC from June 2005 to May 2019 and followed them up until death or censoring in September 2021. Participants lived in 10 New Jersey counties. Data were analyzed between December 2022 and April 2023.

EXPOSURES: A neighborhood socioeconomic status (nSES) index composed of census tract measures (education, income, wealth, employment status, and occupation) was linked to residential addresses at diagnosis. Percentage African ancestry was estimated using the ADMIXTURE program.

MAIN OUTCOMES AND MEASURES: Sequentially adjusted (age adjusted: age and interview year; fully adjusted: age adjusted with individual SES, lifestyle factors, and comorbidities) logistic regression models were fit to estimate associations with tumor subtypes (estrogen receptor-negative [ER-] vs estrogen receptor-positive [ER+]; triple-negative breast cancer [TNBC] vs luminal A), and Cox models were fit for associations with all-cause mortality (ACM) and breast cancer-specific mortality (BCSM). Models for BCSM were fit using Fine-Gray competing risks models, and robust standard errors were used to account for census tract-level clustering.

RESULTS: Among 1575 participants, median (IQR) African ancestry was 85% (76%-90%), and median (IQR) age was 55 (46-63) years. A 10-percentage point increase in African ancestry was associated with higher odds of ER- vs ER+ (adjusted odds ratio [aOR], 1.08; 95% CI, 0.98-1.18) and TNBC vs luminal (aOR, 1.15; 95% CI, 1.02-1.31) tumors, but not with ACM or BCSM. A 1-IQR increase in nSES was associated with lower ACM (adjusted hazard ratio [aHR], 0.76; 95% CI, 0.63-0.93), and the HR for BCSM was less than 1 but not statistically significant (aHR, 0.81; 95% CI, 0.62-1.04) in age-adjusted models, but associations attenuated following further adjustment for potential mediators (individual SES, lifestyles, comorbidities).

CONCLUSIONS AND RELEVANCE: In this cohort study of Black female BC survivors, higher African ancestry was associated with aggressive tumor subtypes. Compared with genetic ancestry, mediating pathways related to social environments may be more important for survival in these patients.

PMID:37647068 | DOI:10.1001/jamanetworkopen.2023.31295

JAMA Netw Open. 2023 Aug 1;6(8):e2331398. doi: 10.1001/jamanetworkopen.2023.31398.

ABSTRACT

IMPORTANCE: The DRAMES (Décès en Relation avec l’Abus de Médicaments Et de Substances) register is a database of drug-related deaths with the aim of identifying the psychoactive substances associated with and estimating the trends in these deaths. Our novel approach is based on the collection of data on all deaths for which toxicology experts have performed analyses.

OBJECTIVE: To describe drug-related deaths in France and report trends over an 11-year period.

DESIGN, SETTING, AND PARTICIPANTS: This case series used a national register to assess 4460 drug-related deaths that occurred from 2011 to 2021 in France. Data analyses were performed from January 1, 2012, to December 31, 2022.

MAIN OUTCOMES AND MEASURES: Demographic characteristics; medical and substance abuse history; forensic autopsy findings; and toxicology reports.

RESULTS: Among the 4460 deceased individuals (mean [SD] age, 37.8 [10.5] years), the mortality rate was highest among men (sex ratio, 4.4:1). Of the deaths involving a single or predominant drug, the legal substitution product, methadone, was the leading cause of death during the entire study period, ahead of heroin-44.7% and 35.9% for methadone vs 15.8% and 21.8% for heroin in 2011 and 2021, respectively. Between 2011 and 2021, most of the drug-related deaths shifted from licit to illicit drugs, and statistically significant variations were found for buprenorphine, cocaine, heroin, methadone, and other licit opioids. Deaths related to polydrug use increased from 23.2% in 2011 to 30.6% in 2021. In this context, opioids remained associated with most deaths, with at least 1 opioid being involved in approximately 9 of 10 cases (85.9%) in 2021. However, the main trend was the dramatic increase in drug combinations with cocaine, from less than one-third of cases in 2011 (30.8%) to more than half in 2021 (57.8%).

CONCLUSIONS AND RELEVANCE: This case series assessment of 4460 drug-related deaths found that opioids used alone or in combination were the main contributor to drug-related deaths, despite having a lower prevalence than other drugs. This finding is similar to that of other countries; however, in France licit methadone was the leading cause of opioid-related deaths (ahead of heroin) during the study period. Deaths associated with use of cannabis, new psychoactive substances, and stimulants (including amphetamine-type stimulants and cocaine, especially in combination) have increased and should be closely monitored.

PMID:37647066 | DOI:10.1001/jamanetworkopen.2023.31398

JAMA Netw Open. 2023 Aug 1;6(8):e2331460. doi: 10.1001/jamanetworkopen.2023.31460.

ABSTRACT

IMPORTANCE: While the Australian National University-Alzheimer Disease Risk Index (ANU-ADRI), Cardiovascular Risk Factors, Aging, and Dementia (CAIDE), and Lifestyle for Brain Health (LIBRA) dementia risk tools have been widely used, a large body of new evidence has emerged since their publication. Recently, Cognitive Health and Dementia Risk Index (CogDrisk) and CogDrisk for Alzheimer disease (CogDrisk-AD) risk tools have been developed for the assessment of dementia and AD risk, respectively, using contemporary evidence; comparison of the relative performance of these risk tools is limited.

OBJECTIVE: To evaluate the performance of CogDrisk, ANU-ADRI, CAIDE, LIBRA, and modified LIBRA (LIBRA with age and sex estimates from ANU-ADRI) in estimating dementia and AD risks (with CogDrisk-AD and ANU-ADRI).

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study obtained data from the Rush Memory and Aging Project (MAP), the Cardiovascular Health Study Cognition Study (CHS-CS), and the Health and Retirement Study-Aging, Demographics and Memory Study (HRS-ADAMS). Participants who were free of dementia at baseline were included. The factors were component variables in the risk tools that included self-reported baseline demographics, medical risk factors, and lifestyle habits. The study was conducted between November 2021 and March 2023, and statistical analysis was performed from January to June 2023.

MAIN OUTCOMES AND MEASURES: Risk scores were calculated based on available factors in each of these cohorts. Area under the receiver operating characteristic curve (AUC) was calculated to measure the performance of each risk score. Multiple imputation was used to assess whether missing data may have affected estimates for dementia risk.

RESULTS: Among the 6107 participants in 3 validation cohorts included for this study, 2184 participants without dementia at baseline were available from MAP (mean [SD] age, 80.0 [7.6] years; 1606 [73.5%] female), 548 participants without dementia at baseline were available from HRS-ADAMS (mean [SD] age, 79.5 [6.3] years; 288 [52.5%] female), and 3375 participants without dementia at baseline were available from CHS-CS (mean [SD] age, 74.8 [4.9] years; 1994 [59.1%] female). In all 3 cohorts, a similar AUC for dementia was obtained using CogDrisk, ANU-ADRI, and modified LIBRA (MAP cohort: CogDrisk AUC, 0.65 [95% CI, 0.61-0.69]; ANU-ADRI AUC, 0.65 [95% CI, 0.61-0.69]; modified LIBRA AUC, 0.65 [95% CI, 0.61-0.69]; HRS-ADAMS cohort: CogDrisk AUC, 0.75 [95% CI, 0.71-0.79]; ANU-ADRI AUC, 0.74 [95% CI, 0.70-0.78]; modified LIBRA AUC, 0.75 [95% CI, 0.71-0.79]; CHS-CS cohort: CogDrisk AUC, 0.70 [95% CI, 0.67-0.72]; ANU-ADRI AUC, 0.69 [95% CI, 0.66-0.72]; modified LIBRA AUC, 0.70 [95% CI, 0.68-0.73]). The CAIDE and LIBRA also provided similar but lower AUCs than the 3 aforementioned tools (eg, MAP cohort: CAIDE AUC, 0.50 [95% CI, 0.46-0.54]; LIBRA AUC, 0.53 [95% CI, 0.48-0.57]). The performance of CogDrisk-AD and ANU-ADRI in estimating AD risks was also similar.

CONCLUSIONS AND RELEVANCE: CogDrisk and CogDrisk-AD performed similarly to ANU-ADRI in estimating dementia and AD risks. These results suggest that CogDrisk and CogDrisk-AD, with a greater range of modifiable risk factors compared with other risk tools in this study, may be more informative for risk reduction.

PMID:37647064 | DOI:10.1001/jamanetworkopen.2023.31460

JAMA Netw Open. 2023 Aug 1;6(8):e2331470. doi: 10.1001/jamanetworkopen.2023.31470.

ABSTRACT

IMPORTANCE: Stroke accounts for 7% of pregnancy-related deaths in the US. As the use of infertility treatment is increasing, many studies have sought to characterize the association of infertility treatment with the risk of stroke with mixed results.

OBJECTIVE: To evaluate the risk of hospitalization from hemorrhagic and ischemic strokes in patients who underwent infertility treatment.

DESIGN, SETTING, AND PARTICIPANTS: This population-based, retrospective cohort study used data abstracted from the Nationwide Readmissions Database, which stores data from all-payer hospital inpatient stays from 28 states across the US, from 2010 and 2018. Eligible participants included individuals aged 15 to 54 who had a hospital delivery from January to November in a given calendar year, and any subsequent hospitalizations from January to December in the same calendar year of delivery during the study period. Statistical analysis was performed between November 2022 and April 2023.

EXPOSURE: Hospital delivery after infertility treatment (ie, intrauterine insemination, assisted reproductive technology, fertility preservation procedures, or use of a gestational carrier) or after spontaneous conception.

MAIN OUTCOMES AND MEASURES: The primary outcome was hospitalization for nonfatal stroke (either ischemic or hemorrhagic stroke) within the first calendar year after delivery. Secondary outcomes included risk of stroke hospitalization at less than 30 days, less than 60 days, less than 90 days, and less than 180 days post partum. Cox proportional hazards regression models were used to estimate associations, which were expressed as hazard ratios (HRs), adjusted for confounders. Effect size estimates were corrected for biases due to exposure misclassification, selection, and unmeasured confounding through a probabilistic bias analysis.

RESULTS: Of 31 339 991 patients, 287 813 (0.9%; median [IQR] age, 32.1 [28.5-35.8] years) underwent infertility treatment and 31 052 178 (99.1%; median [IQR] age, 27.7 [23.1-32.0] years) delivered after spontaneous conception. The rate of stroke hospitalization within 12 months of delivery was 37 hospitalizations per 100 000 people (105 patients) among those who received infertility treatment and 29 hospitalizations per 100 000 people (9027 patients) among those who delivered after spontaneous conception (rate difference, 8 hospitalizations per 100 000 people; 95% CI, -6 to 21 hospitalizations per 100 000 people; HR, 1.66; 95% CI, 1.17 to 2.35). The risk of hospitalization for hemorrhagic stroke (adjusted HR, 2.02; 95% CI, 1.13 to 3.61) was greater than that for ischemic stroke (adjusted HR, 1.55; 95% CI, 1.01 to 2.39). The risk of stroke hospitalization increased as the time between delivery and hospitalization for stroke increased, particularly for hemorrhagic strokes. In general, these associations became larger for hemorrhagic stroke and smaller for ischemic stroke following correction for biases.

CONCLUSIONS AND RELEVANCE: In this cohort study, infertility treatment was associated with an increased risk of stroke-related hospitalization within 12 months of delivery; this risk was evident as early as 30 days after delivery. Timely follow-up in the immediate days post partum and continued long-term follow-up should be considered to mitigate stroke risk.

PMID:37647063 | DOI:10.1001/jamanetworkopen.2023.31470

JAMA Netw Open. 2023 Aug 1;6(8):e2331558. doi: 10.1001/jamanetworkopen.2023.31558.

ABSTRACT

IMPORTANCE: Vitamin D deficiency is commonly associated with sarcopenia; however, the latest International Clinical Practice Guidelines for Sarcopenia do not recommend vitamin D supplementation for sarcopenia owing to a lack of an apparent therapeutic effect on the indices of sarcopenia among participants with replete vitamin D concentration (ie, 25-hydroxyvitamin D [25(OH)D] level >20 ng/mL) from randomized clinical trials. While there is consensus in all vitamin D guidelines that serum levels of 25(OH)D less than 10 ng/mL should be corrected, approximately 30% of the world population’s 25(OH)D levels range from 10 to 20 ng/mL, and it remains unclear whether such suboptimal levels can maintain optimal health, including sarcopenia risk.

OBJECTIVE: To investigate the association of serum 25(OH)D level, especially suboptimal levels, with sarcopenia risk.

DESIGN, SETTING, AND PARTICIPANTS: This genome-wide genetic association study was performed from August 2022 to February 2023 among the 295 489 unrelated European participants from the UK Biobank (2006-2010). Nonlinear and standard mendelian randomization analyses were used to examine the association of serum 25(OH)D concentration with sarcopenia risk.

EXPOSURES: A weighted genetic risk score using 35 unrelated single-nucleotide variants from the UK Biobank and weights from the SUNLIGHT Consortium was selected as an instrumental variable for serum 25(OH)D concentration.

MAIN OUTCOMES AND MEASURES: The primary outcome was sarcopenia, and the secondary outcomes consisted of grip strength, appendicular lean mass index, and gait speed.

RESULTS: The final genetic analyses included 295 489 participants (mean [SD] age, 56.3 [8.1] years; 139 216 female [52.9%]). There was an L-shaped association between genetically predicted serum 25(OH)D concentration and sarcopenia risk. The risk of sarcopenia decreased rapidly as 25(OH)D concentration increased until 20 ng/mL and then leveled off. The odds ratio of sarcopenia for serum 25(OH)D level of 10 vs 20 ng/mL was 1.74 (95% CI, 1.17-2.59). Similar patterns were also observed when the association between serum 25(OH)D concentration and risks of each of the sarcopenia indices were evaluated.

CONCLUSIONS AND RELEVANCE: In this mendelian randomization genetic association study of adults in the UK Biobank, the findings supported a nonlinear association between suboptimal 25(OH)D levels and sarcopenia risk. Randomized clinical trials among participants with suboptimal 25(OH)D levels are required to verify the potential causality.

PMID:37647062 | DOI:10.1001/jamanetworkopen.2023.31558

JAMA Dermatol. 2023 Aug 30. doi: 10.1001/jamadermatol.2023.2955. Online ahead of print.

ABSTRACT

IMPORTANCE: The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression.

OBJECTIVE: To characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma.

DESIGN, SETTING, AND PARTICIPANTS: This single-site case-control study took place at an academic comprehensive cancer center. Fecal samples were collected from systemic treatment-naive patients with stage I to IV melanoma from June 1, 2015, to January 31, 2019, and from healthy volunteers from June 1, 2021, to January 31, 2022. Patients were followed up for disease recurrence until November 30, 2021.

MAIN OUTCOMES AND MEASURES: Fecal microbiota was profiled by 16S ribosomal RNA sequencing. Clinical and pathologic characteristics, treatment, and disease recurrence were extracted from electronic medical records. Fecal microbiome diversity, taxonomic profiles and inferred functional profiles were compared between groups.

RESULTS: A total of 228 participants were enrolled (126 men [55.3%]; median age, 59 [range, 21-90] years), including 49 volunteers without melanoma, 38 patients with early-stage melanoma (29 with stage I or melanoma in situ and 9 with stage II), and 141 with late-stage melanoma (66 with stage III and 75 with stage IV). Community differences were observed between patients with melanoma and volunteers. Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls on univariate analysis (0.19% vs 0.003%; P < .001), but this association was attenuated when adjusted for covariates (log2 fold change of 5.18 vs controls; P = .09). Microbiomes were distinct between patients with early-stage and late-stage melanoma. Early-stage melanoma had a higher alpha diversity (Inverse Simpson Index 14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]; P = .003), and a higher abundance of the genus Roseburia on univariate analysis (2.4% vs 1.2%; P < .001) though statistical significance was lost with covariate adjustment (log2 fold change of 0.86 vs controls; P = .13). Multiple functional pathways were differentially enriched between groups. No associations were observed between the microbial taxa and disease recurrence in patients with stage III melanoma treated with adjuvant immunotherapy.

CONCLUSIONS AND RELEVANCE: The findings of this case-control study suggest that fecal microbiota profiles were significantly different among patients with melanoma and controls and between patients with early-stage and late-stage melanoma. Prospective investigations of the gut microbiome and changes that occur with disease progression may identify future microbial targets for intervention.

PMID:37647056 | DOI:10.1001/jamadermatol.2023.2955

Scand J Med Sci Sports. 2023 Aug 30. doi: 10.1111/sms.14469. Online ahead of print.

ABSTRACT

The role of polymorphism rs9939609 of the FTO gene has been related with fat mass and cardiovascular risk in adults, but it remains unclear in children and adolescents. Hence, the main aim of this study was to determine the FTO polymorphism effects on body composition, cardiorespiratory fitness (CRF), physical activity (PA), inflammatory markers, and cardiovascular risk both in cross-sectional analysis and after two-years of follow-up in children and adolescents. A total of 2129 participants were included in this study. The rs9939609 polymorphism was genotyped. Body composition measurements, CRF, and moderate-to-vigorous PA (MVPA) were determined at baseline and after two-year of follow-up. Moreover, plasma leptin and adiponectin were also determined as inflammatory markers. Furthermore, an index of cardiovascular disease risk factors (CVDRF-I) was calculated. Codominant (TT vs. TA vs. AA) and dominant (AA+AT vs. TT) models were applied for statistical analysis. The results showed a main effect of the FTO genotype on body composition measures in both first and third year (p < 0.05), with lower adiposity in TT compared with AA or AA+AT group. These differences were maintained after accounting for pubertal maturity, sex, age, VO₂ max, and MVPA. Moreover, lower leptin level was observed in TT compared to AA+AT group in the third year. An interaction in Gene*Time*Sex was found in height and neck circumference in dominant model (p = 0.047; p = 0.020, respectively). No differences were found in CRF, MVPA nor CVDRF-I between groups. Hence, homozygous TT allele could be a protective factor against weight gain from early childhood.

PMID:37647022 | DOI:10.1111/sms.14469

Clin Transl Oncol. 2023 Aug 30. doi: 10.1007/s12094-023-03314-2. Online ahead of print.

ABSTRACT

PURPOSE: Uric acid (UA) plays a dual role as an antioxidant and a prooxidant in patients with malignant tumors; however, the relationship between serum UA and malignancy is currently unclear. This study aims to investigate the prognostic value of serum uric acid level before immunotherapy on the efficacy of primary liver cancer (PLC) immunotherapy, which might provide a basis for optimizing the comprehensive treatment scheme.

METHODS: Patients with PLC who were admitted to the First Affiliated Hospital of Gannan Medical College from January 2019 to June 2022 and underwent immunotherapy were collected retrospectively. The difference between serum UA levels in patients with PLC, the correlation between serum UA levels, and the clinical characteristics of patients with PLC were analyzed using the chi-square test, and the survival was estimated using the Kaplan-Meier analysis. To further assess the prognostic significance of UA concentrations, univariate and multivariate Cox regression analyses were performed.

RESULTS: Ninety-nine patients were included in this study cohort. The median follow-up was 7 months (range: 1-29 months), and 76 (76.8%) of the 99 patients with PLC died as of December 31, 2022. Serum UA concentrations ranged from 105 to 670 μmol/l, with a median of 269 μmol/l. The results showed that the serum UA level of patients with PLC was higher than that of healthy subjects (P < 0.001). After subgroup analyses, only male patients with liver cancer had higher serum UA levels than healthy men (P = 0.001). The results of the Kaplan-Meier analysis showed that higher UA levels were associated with poor overall survival (OS) (P = 0.005). In univariate analysis, the OS rate of patients with elevated serum UA levels was significantly lower than the cut-off value (hazard ratio [HR]: 3.191, 95% confidence interval [CI]: 1.456-6.993, P = 0.004), with a median survival time of 151 and 312 days in the high and low serum UA groups, respectively. The results of multivariate analysis showed that the UA level was an independent prognostic factor for immunotherapy in patients with PLC (HR: 3.131, 95% CI: 1.766-5.553, P < 0.001).

CONCLUSIONS: The serum UA level is a reliable biomarker for predicting the prognosis of patients undergoing immunotherapy for PLC, and might provide a basis for the individualized treatment of these patients. Dynamic monitoring of the serum UA level may compensate for the deficiency of the current liver cancer staging system.

PMID:37646984 | DOI:10.1007/s12094-023-03314-2

Clin Transl Oncol. 2023 Aug 30. doi: 10.1007/s12094-023-03301-7. Online ahead of print.

ABSTRACT

BACKGROUND: Brain tumors represent the most common cause of cancer-related death in children. Few studies concerning the palliative phase in children with brain tumors are available.

OBJECTIVES: (i) To describe the palliative phase in children with brain tumors; (ii) to determine whether the use of palliative sedation (PS) depends on the place of death, the age of the patient, or if they received specific palliative care (PC).

METHODS: Retrospective multicenter study between 2010 and 2021, including children from one month to 18 years, who had died of a brain tumor.

RESULTS: 228 patients (59.2% male) from 10 Spanish institutions were included. Median age at diagnosis was 5 years (IQR 2-9) and median age at death was 7 years (IQR 4-11). The most frequent tumors were medulloblastoma (25.4%) and diffuse intrinsic pontine glioma (DIPG) (24.1%). Median number of antineoplastic regimens were 2 (range 0-5 regimens). During palliative phase, 52.2% of the patients were attended by PC teams, while 47.8% were cared exclusively by pediatric oncology teams. Most common concerns included motor deficit (93.4%) and asthenia (87.5%) and communication disorders (89.8%). Most frequently prescribed supportive drugs were antiemetics (83.6%), opioids (81.6%), and dexamethasone (78.5%). PS was administered to 48.7% patients. Most of them died in the hospital (85.6%), while patients who died at home required PS less frequently (14.4%) (p = .01).

CONCLUSION: Children dying from CNS tumors have specific needs during palliative phase. The optimal indication of PS depended on the center experience although, in our series, it was also influenced by the place of death.

PMID:37646983 | DOI:10.1007/s12094-023-03301-7