Nevin Manimala

Trials. 2024 Mar 7;25(1):171. doi: 10.1186/s13063-024-08025-9.

ABSTRACT

BACKGROUND: With an increasing collection of patient-reported outcomes (PROs) to measure health-related quality of life (HRQoL) in oncological patients, there is still a lack of standardised strategies on how to interpret and use these data in patient care. Prior research has shown support for the use of digital PRO monitoring together with alarm systems to notify clinicians when the PRO values are deteriorating. This system has demonstrated advantages in improving HRQoL and increasing survival rates among oncology patients. Hence, we designed the PRO B study, a superiority multi-centre randomised controlled trial, to investigate the effects of alarm-based monitoring in metastatic breast cancer patients in Germany. The study protocol for the PRO B study was published in September 2021, and this manuscript describes a formal statistical analysis plan (SAP) for the PRO B study to improve the transparency and quality of this trial.

METHODS AND DESIGN: The trial aimed to recruit 1000 patients with metastatic breast cancer. However, as of the completion of recruitment on June 15, 2023, we have successfully enrolled 924 patients from 52 breast cancer centres. Patients were 1:1 stratified randomised to the intervention and control groups. App-based PRO questionnaires are sent weekly to the intervention group and every 3 months to the control group. Only patients in the intervention group trigger an alarm if their PRO scores deteriorate, and they are subsequently contacted by the local care team within 48 h. The primary outcome is the fatigue score at 6 months, and secondary outcomes are other HRQoL and overall survival. Evaluation of the superiority of the intervention will be done using a linear mixed model with random intercepts for study centres.

CONCLUSION: This detailed SAP defines the main components of the statistical analysis for the PRO B study to assist the statistician and prevent bias in selecting analysis and reporting findings. Version 1 of the SAP was finalised on January 18, 2024.

TRIAL REGISTRATION: DRKS (German Clinical Trials Register) DRKS00024015 . Registered on February 15, 2021.

PMID:38448904 | DOI:10.1186/s13063-024-08025-9

Appl Neuropsychol Adult. 2024 Mar 6:1-11. doi: 10.1080/23279095.2024.2324126. Online ahead of print.

ABSTRACT

Succession law, which governs the creation and validity of wills, is closely tied to testamentary capacity (TC), the cognitive competence required for a valid will. This study explores TC in acute stroke patients and its connections to demographic and clinical characteristics. The research included first-time stroke patients admitted within 24 hours of symptom onset, meeting specific criteria. Data were collected, and assessment tools like the Addenbrooke’s Cognitive Examination III (ACE-III) and Testamentary Capacity Assessment Tool (TCAT) were used. The study found that TCAT scores were not significantly affected by age or gender but positively correlated with education, the Barthel Index and ACE-III scores. They were negatively associated with National Institutes of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS) scores. Specific cognitive domains, particularly memory and attention, were independent determinants of TCAT scores. This research introduces TCAT as a valuable tool for evaluating testamentary capacity in stroke patients and highlights the multifaceted nature of TC, emphasizing the need for a nuanced approach. As the population ages and complex medical conditions become more prevalent, understanding the interplay between cognitive functioning and testamentary capacity becomes increasingly crucial for both legal and medical professionals.

PMID:38447221 | DOI:10.1080/23279095.2024.2324126

Int Wound J. 2024 Mar;21(3):e14764. doi: 10.1111/iwj.14764.

ABSTRACT

Foot infections, sores or deep tissue damage from diabetes can be a serious psychological and physical injury. This paper aims at making meta-analyses on the therapeutic effects of traditional Chinese medicine (TCM) on diabetic foot ulcers. The Chinese National Knowledge Infrastructure, VIP Database, Wanfang Database and so on, has conducted a randomized controlled trial to evaluate the clinical effect of TCM soaking method for diabetes patients with diabetes. Literature has been determined to be included by computer search and by hand rough checks. The search period was from the creation of the database to October 2023. Review Manager 5.3 was used to analyse the meta data and evaluate it systematically. Altogether, 479 research was conducted in China’s data base and 20 of them were eventually collected for the final statistical analysis. In all, 1361 patients were enrolled in the trials. The results indicated that TCM immersion in diabetic foot resulted in significantly improved obvious wound healing (OR, 3.2; 95% CI, 2.5, 4.09, p < 0.0001); results showed that TCM immersion therapy significantly increased the efficiency of effective wound healing (OR, 4.55; 95% CI, 3.25, 6.37, p < 0.001). Statistical significance was found. Using Egger’s approach to detect publishing bias suggests that there is no risk of publishing bias in terms of marked wound healing and effective healing. Traditional Chinese drug immersion can increase obviously the recovery ratio and the effective recovery ratio of diabetic foot.

PMID:38447218 | DOI:10.1111/iwj.14764

Interdiscip Cardiovasc Thorac Surg. 2024 Mar 6:ivae034. doi: 10.1093/icvts/ivae034. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate if there is still a place for bioprosthetic mitral valve replacement in children by comparing the prosthetic durability and transplant-free survival after bioprosthetic and mechanical mitral valve replacement.

METHODS: We reviewed all mitral valve replacements in children between 1981 and 2020. Bioprosthetic mitral valve replacement cases were individually matched to mechanical mitral valve replacement cases. The incidence rate of a second replacement was calculated using the cumulative incidence function that considered death or transplantation as a competing risk.

RESULTS: The median age at implantation was 3.6 years (IQR, 0.8; 7.9) for the bioprosthetic valve cohort (n = 28) and 3 years (IQR, 1.3; 7.8) for the mechanical valve cohort (n = 28). Seven years after bioprosthetic mitral valve replacement, the cumulative incidence of death or transplantation was 17.9% (95% CI, 6.3-34.1) and the cumulative incidence of a second replacement was 63.6% (95% CI, 39.9-80.1). Seven years after mechanical mitral valve replacement, the cumulative incidence of death or transplantation was 28.6% (95% CI, 13.3-46) and the cumulative incidence of a second replacement was 10.7% (95% CI, 2.6-25.5). 15 years after mechanical mitral valve replacement, the cumulative incidence of death or transplantation was 33.6% (95% CI, 16.2-52.1) and the cumulative incidence of a second replacement was 41.1% (95% CI, 18.4-62.7). The cumulative incidence curves for bioprosthetic and mechanical mitral valve replacement were statistically different for a second valve replacement (P < 0.001) but not for death or transplantation (P = 0.33).

CONCLUSIONS: There is no difference in transplant-free survival after bioprosthetic and mechanical mitral valve replacement in children. The lifespan of bioprosthetic mitral valves remains limited in children because of structural valve failure due to calcification. After 15 years, 40% of mechanical valves were replaced, primarily because of patient-prosthesis mismatch related to somatic growth.

PMID:38447197 | DOI:10.1093/icvts/ivae034

Neurology. 2024 Mar 26;102(6):e209161. doi: 10.1212/WNL.0000000000209161. Epub 2024 Mar 6.

ABSTRACT

BACKGROUND AND OBJECTIVES: Genetic testing is now the standard of care for many neurologic conditions. Health care disparities are unfortunately widespread in the US health care system, but disparities in the utilization of genetic testing for neurologic conditions have not been studied. We tested the hypothesis that access to and results of genetic testing vary according to race, ethnicity, sex, socioeconomic status, and insurance status for adults with neurologic conditions.

METHODS: We analyzed retrospective data from patients who underwent genetic evaluation and testing through our institution’s neurogenetics program. We tested for differences between demographic groups in 3 steps of a genetic evaluation pathway: (1) attending a neurogenetic evaluation, (2) completing genetic testing, and (3) receiving a diagnostic result. We compared patients on this genetic evaluation pathway with the population of all neurology outpatients at our institution, using univariate and multivariable logistic regression analyses.

RESULTS: Between 2015 and 2022, a total of 128,440 patients were seen in our outpatient neurology clinics and 2,540 patients underwent genetic evaluation. Black patients were less than half as likely as White patients to be evaluated (odds ratio [OR] 0.49, p < 0.001), and this disparity was similar after controlling for other demographic factors in multivariable analysis. Patients from the least wealthy quartile of zip codes were also less likely to be evaluated (OR 0.67, p < 0.001). Among patients who underwent evaluation, there were no disparities in the likelihood of completing genetic testing, nor in the likelihood of a diagnostic result after adjusting for age. Analyses restricted to specific indications for genetic testing supported these findings.

DISCUSSION: We observed unequal utilization of our clinical neurogenetics program for patients from marginalized and minoritized demographic groups, especially Black patients. Among patients who do undergo evaluation, all groups benefit similarly from genetic testing when it is indicated. Understanding and removing barriers to accessing genetic testing will be essential to health care equity and optimal care for all patients with neurologic disorders.

PMID:38447117 | DOI:10.1212/WNL.0000000000209161

Neurology. 2024 Apr 9;102(7):e209165. doi: 10.1212/WNL.0000000000209165. Epub 2024 Mar 6.

ABSTRACT

BACKGROUND AND OBJECTIVES: Individuals with prevalent diabetes were known to have a higher risk of dementia and lower cognitive function. However, trends of cognitive function before diabetes and in the short term after new-onset diabetes remain unclear.

METHODS: This study included participants without baseline diabetes from the China Health and Retirement Longitudinal Study. Cognitive tests were conducted at baseline (wave 1) and at least one time from wave 2 (2013) to wave 4 (2018). Cognitive function was assessed using a global cognition score which was the summary measure of 4 cognitive tests. A linear mixed model was constructed to fit the trends in cognitive function before and after diabetes onset and the trends among nondiabetes. The threshold of statistical significance was p < 0.05.

RESULTS: During the 7-year follow-up, 1,207 (9.7% of 12,422, 59.1 ± 8.6 years, 39.9% male participants) participants developed new-onset diabetes. The cognitive function of both the without diabetes group and the diabetes group declined annually during the follow-up. The annual decline rate of the diabetes group before diabetes onset was similar to that of the without diabetes group during the whole follow-up period. After diabetes onset, participants experienced statistically significant faster cognitive declines in global cognition (-0.023 SD/year; 95% CI -0.043 to -0.004; p = 0.019) and visuospatial abilities test (-0.036 SD/year; -0.061 to -0.011; p = 0.004), but not in tests of episodic memory (-0.018 SD/year; -0.041 to 0.004; p = 0.116), attention and calculation (-0.017 SD/year; -0.037 to 0.003; p = 0.090), or orientation (0.001 SD/year; -0.018 to 0.020; p = 0.894), compared with the cognitive slope before diabetes. In subgroup analysis, compared with those who developed diabetes between 45-54 years, those developing diabetes older (55-64 years, p for interaction = 0.701; 65-74 years, p for interaction = 0.996) did not demonstrate different rates of global cognitive decline after diabetes.

DISCUSSION: Individuals experienced faster rate of cognitive decline in a few years after diabetes onset, but not during the prediabetes period. Age did not modify the effect of diabetes on postdiabetes cognitive decline. Efforts in eliminating the adverse impacts on cognition should be started on diagnosis of diabetes.

PMID:38447106 | DOI:10.1212/WNL.0000000000209165

Neurology. 2024 Apr 9;102(7):e209168. doi: 10.1212/WNL.0000000000209168. Epub 2024 Mar 6.

ABSTRACT

BACKGROUND AND OBJECTIVES: The association of statin initiation with incident Alzheimer disease (AD) dementia and cognitive decline by the APOE ε4 allele is unknown. Our objective was to examine whether the association of statin initiation with incident AD dementia and cognitive decline differs by the APOE ε4 allele.

METHODS: This population-based longitudinal cohort study was conducted in 4 urban communities in Chicago, IL, United States, consisting of 4,807 participants. Statin initiation is based on the inspection of medications during home assessments. Clinical diagnosis for incident AD used the NINCDS-ADRDA criteria, and longitudinal measurements of global cognition consisted of episodic memory, perceptual speed, and the Mini-Mental State Examination tests.

RESULTS: The study participants had a mean age of 72 years, consisting of 63% female individuals and 61% non-Hispanic Black individuals. During the study period, 1,470 (31%) participants reported statin initiation. In a covariate-adjusted competing risk model, statin initiation was associated with a reduced risk of incident clinical AD [hazard ratio (HR) 0.81 (95% CI 0.70-0.94)] compared with nonusers. This association was statistically significantly lower (p interaction = 0.015) among participants with the APOE ε4 allele [HR 0.60 (95% CI 0.49-0.74)] compared with those without the APOE ε4 allele [HR 0.96 (95% CI 0.82-1.12)]. The annual decline in global cognition (β = 0.021, 95% CI 0.007-0.034) and episodic memory (β = 0.020, 95% CI 0.007-0.033) was also substantially slower among participants with the APOE ε4 allele after statin initiation compared with nonusers. However, the association of statin initiation with cognitive decline was not significant among those without the APOE ε4 allele.

DISCUSSION: Our findings suggest that statins might be associated with a lower risk of incident AD among individuals with the APOE ε4 allele. The benefits of statin therapy need further consideration in randomized clinical trials, especially among those with the APOE ε4 allele.

CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among those aged 65 years or older, statin initiation was associated with a reduced risk of Alzheimer disease, especially in the presence of an APOE-e4 allele.

PMID:38447103 | DOI:10.1212/WNL.0000000000209168

AIDS Care. 2024 Mar 6:1-10. doi: 10.1080/09540121.2024.2325100. Online ahead of print.

ABSTRACT

Transitioning from pediatric to adult care remains a challenge for adolescents and young adults with perinatally-acquired HIV (AYA-PHIV). We assessed treatment outcomes and mortality among Thai AYA-PHIV. The study included AYA-PHIV who reached age 18-24 years who started antiretroviral treatment during childhood at five pediatric HIV clinics across Thailand. From November 2020-July 2021, data were gathered from a cohort database, medical records, and the Thai National AIDS Program. Of 811 eligible AYA-PHIV, 93% were alive; median age 22.3 years (IQR 20.6-23.7), treatment duration 16.1 years (IQR 13.4-18.0). Current HIV care was provided in adults (71%) and pediatric clinics (29%). Treatment regimens included non-nucleoside reverse transcriptase inhibitors (55%), protease inhibitors (36%), and integrase inhibitors (8%); 78% had HIV RNA <200 copies/ml. Of the 7.0% who died, median age at death was 20.8 years (IQR 20.6-22.1); 88% were AIDS-related death. Mortality after age 18 was 1.76 per 100-person years (95% confidence interval 1.36-2.28). Those with CD4 <200 cell/mm³ at age 15 had higher risk of mortality (adjusted hazard ratio 6.16, 95% CI 2.37-16.02). In conclusion, the high mortality among Thai AYA-PHIV indicated the need for better systems to support AYA-PHIV during the transition to adulthood.

PMID:38447043 | DOI:10.1080/09540121.2024.2325100

Int J Cancer. 2024 Mar 6. doi: 10.1002/ijc.34911. Online ahead of print.

ABSTRACT

Human papillomavirus can be contracted by sexually active women. However, only a small proportion of these infections persist and have the potential to progress into cervical cancers, indicating a significant involvement of the immune system in cervical cancer development. Despite this, our understanding of the precise contributions of genes from different immune cell types in cervical cancers remains limited. Therefore, the primary objective of our study was to investigate the potential causal relationships between specific immune cell genes and the development of cervical cancers. By accessing expression quantitative trait loci datasets of 14 distinct immune cell types and genome wide association study of cervical cancers, we employed the summary data-based Mendelian randomization (SMR) along with multi-single nucleotide polymorphism (SNP)-based SMR to identify significant genes associated with cervical cancers. Colocalization analysis was further conducted to explore the shared genetic causality. A total of 10 genes across 11 immune cell types (26 significant gene-trait associations) were found to be associated with cervical cancers after false discovery rate correction. Notably, the ORMDL3, BRK1 and HMGN1 gene expression levels showed significant association with cervical cancer in specific immune cell types, respectively. These associations were supported by strong evidence of colocalization analyses. Our study has identified several genes in different immune cells that were associated with cervical cancer. However, further research is necessary to confirm these findings and provide more comprehensive insights into the association between these gene expressions and cervical cancer risk.

PMID:38447016 | DOI:10.1002/ijc.34911

Med Care. 2024 Feb 27. doi: 10.1097/MLR.0000000000001980. Online ahead of print.

ABSTRACT

BACKGROUND: Using federal funds from the 2009 Health Information Technology for Economic and Clinical Health Act, the Centers for Medicare and Medicaid Services funded the 2011-2021 Medicaid electronic health record (EHR) incentive programs throughout the country.

OBJECTIVE: Identify the market factors associated with Meaningful Use (MU) of EHRs after primary care providers (PCPs) enrolled in the Florida-EHR incentives program through Adopting, Improving, or Upgrading (AIU) an EHR technology.

RESEARCH DESIGN: Retrospective cohort study using 2011-2018 program records for 8464 Medicaid providers.

MAIN OUTCOME: MU achievement after first-year incentives.

INDEPENDENT VARIABLES: The resource dependence theory and the information uncertainty perspective were used to generate key-independent variables, including the county’s rurality, educational attainment, poverty, health maintenance organization penetration, and number of PCPs per capita.

ANALYTICAL APPROACH: All the county rates were converted into 3 dichotomous measures corresponding to high, medium, and low terciles. Descriptive and bivariate statistics were calculated. A generalized hierarchical linear model was used because MU data were clustered at the county level (level 2) and measured at the practice level (level 1).

RESULTS: Overall, 41.9% of Florida Medicaid providers achieved MU after receiving first-year incentives. Rurality was positively associated with MU (P<0.001). Significant differences in MU achievements were obtained when we compared the “high” terciles with the “low” terciles for poverty rates (P=0.002), health maintenance organization penetration rates (P=0.02), and number of PCPs per capita (P=0.01). These relationships were negative.

CONCLUSIONS: Policy makers and health care managers should not ignore the contribution of market factors in EHR adoption.

PMID:38447010 | DOI:10.1097/MLR.0000000000001980