Nevin Manimala

JMIR Res Protoc. 2024 Jul 2;13:e51381. doi: 10.2196/51381.

ABSTRACT

BACKGROUND: Starting in 2010, the epidermal growth factor receptor (EGFR) kinase inhibitors erlotinib and gefitinib were introduced into routine use in Aotearoa New Zealand (NZ) for treating advanced lung cancer, but their impact in this setting is unknown.

OBJECTIVE: The study described in this protocol aims to understand the effectiveness and safety of these new personalized lung cancer treatments and the contributions made by concomitant medicines and other factors to adverse outcomes in the general NZ patient population. A substudy aimed to validate national electronic health databases as the data source and the methods for determining patient eligibility and identifying outcomes and variables.

METHODS: This study will include all NZ patients with advanced EGFR mutation-positive lung cancer who were first dispensed erlotinib or gefitinib before October 1, 2020, and followed until death or for at least 1 year. Routinely collected health administrative and clinical data will be collated from national electronic cancer registration, hospital discharge, mortality registration, and pharmaceutical dispensing databases by deterministic data linkage using National Health Index numbers. The primary effectiveness and safety outcomes will be time to treatment discontinuation and serious adverse events, respectively. The primary variable will be high-risk concomitant medicines use with erlotinib or gefitinib. For the validation substudy (n=100), data from clinical records were compared to those from national electronic health databases and analyzed by agreement analysis for categorical data and by paired 2-tailed t tests for numerical data.

RESULTS: In the validation substudy, national electronic health databases and clinical records agreed in determining patient eligibility and for identifying serious adverse events, high-risk concomitant medicines use, and other categorical data with overall agreement and κ statistic of >90% and >0.8000, respectively; for example, for the determination of patient eligibility, the comparison of proxy and standard eligibility criteria applied to national electronic health databases and clinical records, respectively, showed overall agreement and κ statistic of 96% and 0.8936, respectively. Dates for estimating time to treatment discontinuation and other numerical variables and outcomes showed small differences, mostly with nonsignificant P values and 95% CIs overlapping with zero difference; for example, for the dates of the first dispensing of erlotinib or gefitinib, national electronic health databases and clinical records differed on average by approximately 4 days with a nonsignificant P value of .33 and 95% CIs overlapping with zero difference. As of May 2024, the main study is ongoing.

CONCLUSIONS: A protocol is presented for a national whole-of-patient-population retrospective cohort study designed to describe the safety and effectiveness of erlotinib and gefitinib during their first decade of routine use in NZ for treating EGFR mutation-positive lung cancer. The validation substudy demonstrated the feasibility and validity of using national electronic health databases and the methods for determining patient eligibility and identifying the study outcomes and variables proposed in the study protocol.

TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000998549; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368928.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51381.

PMID:38954434 | DOI:10.2196/51381

Cogn Neuropsychiatry. 2024 Jul 2:1-11. doi: 10.1080/13546805.2024.2367269. Online ahead of print.

ABSTRACT

INTRODUCTION: In schizophrenia, social functioning and personal recovery are pivotal outcomes potentially influenced by cognitive biases such as Jumping to Conclusions (JTC). Despite their significance, the relationship between JTC, social functioning, and personal recovery remains unclear. This study aims to investigate this relationship to inform tailored interventions for schizophrenia management.

METHODS: Data were collected from 94 schizophrenia patients using standardised measures. The Beads Task assessed JTC, whereas the Brief PANSS, TMT-J, SLOF-J, and RAS-J evaluated psychiatric symptoms, neurocognitive functioning, social functioning, and personal recovery, respectively. Statistical analyses included correlation and hierarchical regression.

RESULTS: Correlation analyses revealed a significant negative correlation between JTC and personal recovery (r = -0.27, p < 0.05). Hierarchical regression indicated JTC as a significant negative predictor of personal recovery (β = -0.33, p = 0.01). No significant correlation was found between JTC and social functioning.

DISCUSSION: Increased JTC was associated with lower levels of personal recovery in schizophrenia patients, independent of demographic and clinical factors. In the case of individuals with schizophrenia who demonstrate JTC, there is a potential to suggest the paradox of insight or apparent personal recovery scores.

PMID:38954431 | DOI:10.1080/13546805.2024.2367269

JAMA Netw Open. 2024 Jul 1;7(7):e2418234. doi: 10.1001/jamanetworkopen.2024.18234.

ABSTRACT

IMPORTANCE: Current evidence is conflicting for associations of extended-infusion β-lactam (EI-BL) therapy with clinical outcomes.

OBJECTIVE: To investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI).

DESIGN, SETTING, AND PARTICIPANTS: This cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion β-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023.

EXPOSURES: EI-BL (ie, ≥3-hour infusion).

MAIN OUTCOMES AND MEASURES: EI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the β-lactam used to treat the index GN-BSI).

RESULTS: Among the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35).

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.

PMID:38954416 | DOI:10.1001/jamanetworkopen.2024.18234

JAMA Netw Open. 2024 Jul 1;7(7):e2418821. doi: 10.1001/jamanetworkopen.2024.18821.

ABSTRACT

IMPORTANCE: Socioeconomically disadvantaged individuals (ie, those with low socioeconomic status [SES]) have difficulty quitting smoking and may benefit from incentive-based cessation interventions.

OBJECTIVES: To evaluate the impact of incentivizing smoking abstinence on smoking cessation among adults with low SES.

DESIGN, SETTING, AND PARTICIPANTS: This study used a 2-group randomized clinical trial design. Data collection occurred between January 30, 2017, and February 7, 2022. Participants included adults with low SES who were willing to undergo smoking cessation treatment. Data were analyzed from April 18, 2023, to April 19, 2024.

INTERVENTIONS: Participants were randomized to usual care (UC) for smoking cessation (counseling plus pharmacotherapy) or UC plus abstinence-contingent financial incentives (UC plus FI).

MAIN OUTCOMES AND MEASURES: The primary outcome was biochemically verified 7-day point prevalence smoking abstinence (PPA) at 26 weeks after the quit date. Secondary outcomes included biochemically verified 7-day PPA at earlier follow-ups, 30-day PPA at 12 and 26 weeks, repeated 7-day PPA, and continuous abstinence. Multiple approaches were employed to handle missing outcomes at follow-up, including categorizing missing data as smoking (primary), complete case analysis, and multiple imputation.

RESULTS: The 320 participants had a mean (SD) age of 48.9 (11.6) and were predominantly female (202 [63.1%]); 82 (25.6%) were Black, 15 (4.7%) were Hispanic, and 200 (62.5%) were White; and 146 (45.6%) participated during the COVID-19 pandemic. Overall, 161 were randomized to UC and 159 were randomized to UC plus FI. After covariate adjustment with missing data treated as smoking, assignment to UC plus FI was associated with a greater likelihood of 7-day PPA at the 4-week (adjusted odds ratio [AOR], 3.11 [95% CI, 1.81-5.34]), 8-week (AOR, 2.93 [95% CI, 1.62-5.31]), and 12-week (AOR, 3.18 [95% CI, 1.70-5.95]) follow-ups, but not at the 26-week follow-up (22 [13.8%] vs 14 [8.7%] abstinent; AOR, 1.79 [95% CI, 0.85-3.80]). However, the association of group assignment with smoking cessation reached statistical significance at all follow-ups, including 26 weeks, with multiple imputation (37.37 [23.5%] in the UC plus FI group vs 19.48 [12.1%] in the UC group were abstinent; AOR, 2.29 [95% CI, 1.14-4.63]). Repeated-measures analyses indicated that participants in the UC plus FI group were significantly more likely to achieve PPA across assessments through 26 weeks with all missing data estimation methods. Other secondary cessation outcomes also showed comparable patterns across estimation methods. Participants earned a mean (SD) of $72 ($90) (of $250 possible) in abstinence-contingent incentives. Participation during the COVID-19 pandemic reduced the likelihood of cessation across assessments.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, incentivizing smoking cessation did not increase cessation at 26 weeks when missing data were treated as smoking; however, the UC plus FI group had greater odds of quitting at follow-ups through 12 weeks. Cessation rates were higher for the UC plus FI group at all follow-ups through 26 weeks when multiple imputation was used to estimate missing outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02737566.

PMID:38954415 | DOI:10.1001/jamanetworkopen.2024.18821

JAMA Netw Open. 2024 Jul 1;7(7):e2419696. doi: 10.1001/jamanetworkopen.2024.19696.

ABSTRACT

IMPORTANCE: Gender-affirming hormone treatment (GAHT) is a common therapy for transgender individuals to reduce gender dysphoria and improve quality of life. Clarifying the long-term effects of GAHT remains a priority in transgender health research.

OBJECTIVE: To explore whether sex hormones (estradiol and testosterone) are associated with the development of metabolic syndrome in transgender veterans compared with cisgender veterans.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, longitudinal cohort study used International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes for gender dysphoria from the Veterans Health Administration national database to identify transfeminine and transmasculine veterans receiving documented feminizing (estradiol) or masculinizing (testosterone) treatment from January 1, 2006, to December 31, 2019, and for whom the GAHT initiation date and metabolic syndrome component-related data were available. Transgender veterans were matched to cisgender referents.

EXPOSURE: Gender-affirming hormone treatment.

MAIN OUTCOMES AND MEASURES: Metabolic syndrome z-scores were calculated based on body mass index, systolic blood pressure, and levels of high-density lipoprotein cholesterol, triglycerides, and blood glucose. Changes in mean z-scores were compared among the transgender and cisgender groups before and after the index date (corresponding to GAHT initiation) using a repeated-measures analysis of variance model.

RESULTS: The cohort included 1290 participants: 645 transgender (494 [38.3%] transfeminine, 151 [11.7%] transmasculine) and 645 cisgender (280 [21.7%] female, 365 [28.3%] male). Mean (SD) age at the index date was 41.3 (13.2) years. Metabolic syndrome z-scores changed significantly over time and differed significantly across groups. Overall, transmasculine veterans had the greatest percentage increase in mean (SEM) z-scores after vs before the index date (298.0% [57.0%]; P < .001), followed by cisgender females (108.3% [27.5%]; P < .001), cisgender males (49.3% [27.5%]; P = .02), and transfeminine persons (3.0% [10.7%]; P = .77).

CONCLUSIONS AND RELEVANCE: In this cohort study, in both cisgender and transgender veterans, estradiol was associated with reduced metabolic syndrome risk, whereas testosterone was associated with increased risk. However, transmasculine individuals had the greatest risk and transfeminine individuals had the lowest risk of metabolic syndrome associated with these hormones. This is relevant for the management of metabolic syndrome risk factors in cisgender and transgender individuals and to potentially predict the risk of atherosclerotic cardiovascular disease, type 2 diabetes, systolic hypertension, insulin resistance, and nonalcoholic fatty liver disease.

PMID:38954413 | DOI:10.1001/jamanetworkopen.2024.19696

JAMA Netw Open. 2024 Jul 1;7(7):e2419771. doi: 10.1001/jamanetworkopen.2024.19771.

ABSTRACT

IMPORTANCE: Current research in epigenetic age acceleration (EAA) is limited to non-Hispanic White individuals. It is imperative to improve inclusivity by considering racial and ethnic minorities in EAA research.

OBJECTIVE: To compare non-Hispanic Black with non-Hispanic White survivors of childhood cancer by examining the associations of EAA with cancer treatment exposures, potential racial and ethnic disparity in EAA, and mediating roles of social determinants of health (SDOH).

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, participants were from the St Jude Lifetime Cohort, which was initiated in 2007 with ongoing follow-up. Eligible participants included non-Hispanic Black and non-Hispanic White survivors of childhood cancer treated at St Jude Children’s Research Hospital between 1962 and 2012 who had DNA methylation data. Data analysis was conducted from February 2023 to May 2024.

EXPOSURE: Three treatment exposures for childhood cancer (chest radiotherapy, alkylating agents, and epipodophyllotoxin).

MAIN OUTCOMES AND MEASURES: DNA methylation was generated from peripheral blood mononuclear cell-derived DNA. EAA was calculated as residuals from regressing Levine or Horvath epigenetic age on chronological age. SDOH included educational attainment, annual personal income, and the socioeconomic area deprivation index (ADI). General linear models evaluated cross-sectional associations of EAA with race and ethnicity (non-Hispanic Black and non-Hispanic White) and/or SDOH, adjusting for sex, body mass index, smoking, and cancer treatments. Adjusted least square means (ALSM) of EAA were calculated for group comparisons. Mediation analysis treated SDOH as mediators with average causal mediation effect (ACME) calculated for the association of EAA with race and ethnicity.

RESULTS: Among a total of 1706 survivors including 230 non-Hispanic Black survivors (median [IQR] age at diagnosis, 9.5 [4.3-14.3] years; 103 male [44.8%] and 127 female [55.2%]) and 1476 non-Hispanic White survivors (median [IQR] age at diagnosis, 9.3 [3.9-14.6] years; 766 male [51.9%] and 710 female [48.1%]), EAA was significantly greater among non-Hispanic Black survivors (ALSM = 1.41; 95% CI, 0.66 to 2.16) than non-Hispanic White survivors (ALSM = 0.47; 95% CI, 0.12 to 0.81). Among non-Hispanic Black survivors, EAA was significantly increased among those exposed to chest radiotherapy (ALSM = 2.82; 95% CI, 1.37 to 4.26) vs those unexposed (ALSM = 0.46; 95% CI, -0.60 to 1.51), among those exposed to alkylating agents (ALSM = 2.33; 95% CI, 1.21 to 3.45) vs those unexposed (ALSM = 0.95; 95% CI, -0.38 to 2.27), and among those exposed to epipodophyllotoxins (ALSM = 2.83; 95% CI, 1.27 to 4.40) vs those unexposed (ALSM = 0.44; 95% CI, -0.52 to 1.40). The association of EAA with epipodophyllotoxins differed by race and ethnicity (β for non-Hispanic Black survivors, 2.39 years; 95% CI, 0.74 to 4.04 years; β for non-Hispanic White survivors, 0.68; 95% CI, 0.05 to 1.31 years) and the difference was significant (1.77 years; 95% CI, 0.01 to 3.53 years; P for interaction = .049). Racial and ethnic disparities in EAA were mediated by educational attainment (<high school vs ≥college, ACME = 0.13; high school vs ≥college, ACME = 0.07; mediation = 22.71%) and ADI (ACME = 0.24; mediation = 22.16%).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of childhood cancer survivors, race and ethnicity moderated the association of EAA with epipodophyllotoxin exposure and racial and ethnic differences in EAA were partially mediated by educational attainment and ADI, indicating differential treatment toxic effects by race and ethnicity. These findings suggest that improving social support systems may mitigate socioeconomic disadvantages associated with even greater accelerated aging and reduce health disparities among childhood cancer survivors.

PMID:38954412 | DOI:10.1001/jamanetworkopen.2024.19771

Longit Life Course Stud. 2024 Mar 18;15(3):394-406. doi: 10.1332/17579597Y2024D000000014.

ABSTRACT

This study aims to evaluate the temporal trend in the quality of cause-of-death data and garbage code profiles and to determine its association with socio-economic status in Serbia. A longitudinal study was assessed using data from mortality registers from 2005 to 2019. Computer application Analysis of Causes of National Deaths for Action (ANACONDA) calculates the distribution of garbage codes by severity and composite quality indicator: Vital Statistics Performance Index for Quality (VSPI(Q)). A relationship between VSPI(Q) and country development was estimated by analysing two socio-economic indicators: the Socio-demographic Index and the Human Development Index (HDI). Serbia indicates progress in strengthening cause-of-death statistics. The steady upward trend of the VSPI(Q) index has risen from 55.6 (medium quality) to 70.2 (high quality) over the examined years. Significant reduction of ‘Insufficiently specified causes with limited impact’ (Level 4) and an increase in the trend of ‘High-impact garbage codes’ (Levels 1 to 3) were evident. Decreased deaths of no policy value (annual percentage change of -1.41%) have manifested since 2014. A strong positive association between VSPI(Q) and socio-economic indicators was assessed, where the HDI has shown a stronger association with VSPI(Q). Improved socio-economic conditions on the national level are followed by enhanced cause-of-death data quality. Upcoming actions to improve quality should be directed at high-impact garbage codes. The study underlines the need to prioritise the education and training of physicians with a crucial role in death certification to overcome many cause-of-death quality issues identified in this assessment.

PMID:38954409 | DOI:10.1332/17579597Y2024D000000014

ACS Appl Bio Mater. 2024 Jul 2. doi: 10.1021/acsabm.4c00484. Online ahead of print.

ABSTRACT

Wastewater-based epidemiology (WBE) can help mitigate the spread of respiratory infections through the early detection of viruses, pathogens, and other biomarkers in human waste. The need for sample collection, shipping, and testing facilities drives up the cost of WBE and hinders its use for rapid detection and isolation in environments with small populations and in low-resource settings. Given the ubiquitousness and regular outbreaks of respiratory syncytial virus, SARS-CoV-2, and various influenza strains, there is a rising need for a low-cost and easy-to-use biosensing platform to detect these viruses locally before outbreaks can occur and monitor their progression. To this end, we have developed an easy-to-use, cost-effective, multiplexed platform able to detect viral loads in wastewater with several orders of magnitude lower limit of detection than that of mass spectrometry. This is enabled by wafer-scale production and aptamers preattached with linker molecules, producing 44 chips at once. Each chip can simultaneously detect four target analytes using 20 transistors segregated into four sets of five for each analyte to allow for immediate statistical analysis. We show our platform’s ability to rapidly detect three virus proteins (SARS-CoV-2, RSV, and Influenza A) and a population normalization molecule (caffeine) in wastewater. Going forward, turning these devices into hand-held systems would enable wastewater epidemiology in low-resource settings and be instrumental for rapid, local outbreak prevention.

PMID:38954405 | DOI:10.1021/acsabm.4c00484

Curr Med Res Opin. 2024 Jul 2:1-10. doi: 10.1080/03007995.2024.2374510. Online ahead of print.

ABSTRACT

Background: Post-COVID-19 condition (PCC), also known as “long COVID,” is characterized by persistent symptoms, negatively affecting the well-being of individuals with PCC. Anhedonia (i.e., reduced capacity for pleasure) and compromised psychosocial functioning are notable symptoms in those with PCC. We aimed to provide insights to understand the effects of anhedonia and impaired psychosocial functioning of patients with PCC.Methods: This post-hoc analysis used data from an 8-week, double-blind, randomized, placebo-controlled trial which evaluated vortioxetine for cognitive deficits in individuals with PCC (Clinicaltrials.gov Identifier: NCT05047952). A total of 147 eligible participants were randomly assigned to receive vortioxetine or matching placebo over eight weeks of double-blind treatment. Our study investigated the relationship between anhedonia, assessed by the Snaith-Hamilton Pleasure Scale (SHAPS), and psychosocial functioning, measured with the Post-COVID Functional Status (PCFS) scale. The analysis was conducted using a generalized linear model, with adjustments for relevant covariates such as age, sex, education, suspected versus confirmed COVID diagnosis, MDD diagnosis, and alcohol consumption.Results: Of the 147 participants, 143 participants had available baseline data for analysis. We observed that baseline PCFS score was statistically significantly positively correlated to baseline SHAPS score (β = 0.070, p = 0.045, 95% CI).Discussions: Our analysis revealed a significant relationship between measures of anhedonia and psychosocial functioning in adults with PCC. Strategies that aim to improve patient-reported outcomes with PCC need to prioritize the prevention and treatment of hedonic disturbances in patients experiencing PCC.

PMID:38954402 | DOI:10.1080/03007995.2024.2374510

Ir J Med Sci. 2024 Jul 2. doi: 10.1007/s11845-024-03741-2. Online ahead of print.

ABSTRACT

OBJECTIVE: To validate the predictive performance of the THRIVE, ASTRAL, and iScore scales for clinical functional outcomes following mechanical thrombectomy (MT) for acute ischemic stroke (AIS).

METHODS: A total of 111 patients meeting the inclusion criteria were included in this study, with 59 (53.2%) having a good prognosis and 52 (46.8%) having a poor prognosis. MedCalc software was applied to plot receiver operating characteristic (ROC) curves, calculate the area under the curve (AUC), and compare the predictive efficacy of the three scales two by two using Delong text. Statistical significance was defined as P_c < 0.05.

RESULTS: Logistic binary regression multifactorial analysis revealed that iScore is one of the poor predictors of prognosis in patients with MT. The AUC values for the THRIVE, ASTRAL, and iScore scales in predicting prognosis after MT were found to be 0.713, 0.738, and 0.820, respectively.

CONCLUSION: The iScore is a reliable tool for assessing the poor prognosis of MT in patients with AIS.

PMID:38954327 | DOI:10.1007/s11845-024-03741-2