Nevin Manimala

J Comput Biol. 2023 Nov 6. doi: 10.1089/cmb.2023.0191. Online ahead of print.

ABSTRACT

The itca Python package offers an information-theoretic criterion to assist practitioners in combining ambiguous outcome labels by balancing the tradeoff between prediction accuracy and classification resolution. This article provides instructions for installing the itca Python package, demonstrates how to evaluate the criterion, and showcases its application in real-world scenarios for guiding the combination of ambiguous outcome labels.

PMID:37930802 | DOI:10.1089/cmb.2023.0191

Mil Med. 2023 Oct 31:usad414. doi: 10.1093/milmed/usad414. Online ahead of print.

ABSTRACT

ABSTRACT: IntroductionWe aimed to identify injury-related risk factors for secondary cataract incidence after eye and brain injury and polytrauma. We also examined the effect of direct and indirect eye injury management on cataract diagnosis and treatment. Prevention or mitigation strategies require knowledge of the causes and types of combat injuries, which will enable more appropriate targeting of resources toward prevention and more efficient management of such injuries.

MATERIALS AND METHODS: Data were gathered from the Military Health System using the Military Health System Management and Analysis Reporting Tool (M2) between 2017 and 2021 from inpatient and outpatient Service Members (SMs) (active duty and National Guard). The date of the first cataract diagnosis was tracked to estimate the annual incidence rate, and it was longitudinally linked to any prior diagnosis of ocular trauma (OT), traumatic brain injury (TBI), or polytrauma to calculate the relative risk. International Classification of Disease codes, 10th Revision, were used to identify those diagnosed with cataracts, TBI, and polytrauma. Defense and Veterans Eye Injury and Vision Registry data were used to examine SMs who sustained ocular injuries from 2003-2020 and who may have had cataract surgery following a cataract diagnosis.

RESULTS: The relative risk of traumatic cataract formation from OT, TBI, and polytrauma are 5.71 (95% CI, 5.05-6.42), 2.32 (95% CI, 2.03-2.63), and 8.95 (95% CI, 6.23-12.38), respectively. Traumatic cataracts in SMs more commonly result from open-globe injuries (70%) than closed-globe injuries (30%). By specific sub-injury type, traumatic cataracts occur most frequently from intraocular foreign bodies (22%). More than 400 patients in the cohort suffered from TBI and traumatic cataracts, more than 300 from OT and cataracts, and more than 20 from polytrauma and cataracts. The battlefield is the riskiest environment for trauma exposure, with 62% of OT occurring in combat. There was a statistically significant difference between the mean visual acuity value before cataract surgery (M = 1.17, SD = 0.72) and the mean visual acuity value after cataract surgery (M = 0.44, SD = 0.66, P < .001).

CONCLUSION: Traumatic cataracts often occur in SMs who sustain ocular injuries. New to the literature is that relationships exist between traumatic cataract formation and nonglobe trauma, specifically TBI and polytrauma. Ocular injury calls for an ophthalmic examination. A low threshold should exist for routine ocular exam consultation in the setting of TBI and polytrauma. Separately, polytrauma patients should undergo a review of systems questions, particularly questions about the ocular and visual pathways. A positive response to screening warrants further investigation of possible ocular pathology, including traumatic cataract formation. Cataract surgery is an effective treatment in improving the vision of SMs who suffer from traumatic cataracts. Constant effort must be made to limit occurrences of occupation-related traumatic cataracts.

PMID:37930775 | DOI:10.1093/milmed/usad414

JMIR Form Res. 2023 Nov 6;7:e48864. doi: 10.2196/48864.

ABSTRACT

BACKGROUND: Social isolation and loneliness affect 61% of US adults and are associated with significant increases in excessive mental and physical morbidity and mortality. Annual health care spending is US $1643 higher for socially isolated individuals than for those not socially isolated.

OBJECTIVE: We prospectively evaluated the effects of participation with a digitally enabled peer support intervention on loneliness, depression, anxiety, and health-related quality of life among adults with loneliness.

METHODS: Adults aged 18 years and older living in Colorado were recruited to participate in a peer support program via social media campaigns. The intervention included peer support, group coaching, the ability to become a peer helper, and referral to other behavioral health resources. Participants were asked to complete surveys at baseline, 30, 60, and 90 days, which included questions from the validated University of California, Los Angeles Loneliness Scale, Patient Health Questionnaire 2-Item Scale, General Anxiety Disorder 7-Item Scale, and a 2-item measure assessing unhealthy days due to physical condition and mental condition. A growth curve modeling procedure using multilevel regression analyses was conducted to test for linear changes in the outcome variables from baseline to the end of the intervention.

RESULTS: In total, 815 ethnically and socially diverse participants completed registration (mean age 38, SD 12.7; range 18-70 years; female: n=310, 38%; White: n=438, 53.7%; Hispanic: n=133, 16.3%; Black: n=51, 6.3%; n=263, 56.1% had a high social vulnerability score). Participants most commonly joined the following peer communities: loneliness (n=220, 27%), building self-esteem (n=187, 23%), coping with depression (n=179, 22%), and anxiety (n=114, 14%). Program engagement was high, with 90% (n=733) engaged with the platform at 60 days and 86% (n=701) at 90 days. There was a statistically (P<.001 for all outcomes) and clinically significant improvement in all clinical outcomes of interest: a 14.6% (mean 6.47) decrease in loneliness at 90 days; a 50.1% (mean 1.89) decline in depression symptoms at 90 days; a 29% (mean 1.42) reduction in anxiety symptoms at 90 days; and a 13% (mean 21.35) improvement in health-related quality of life at 90 days. Based on changes in health-related quality of life, we estimated a reduction in annual medical costs of US $615 per participant. The program was successful in referring participants to behavioral health educational resources, with 27% (n=217) of participants accessing a resource about how to best support those experiencing psychological distress and 15% (n=45) of women accessing a program about the risks of excessive alcohol use.

CONCLUSIONS: Our results suggest that a digitally enabled peer support program can be effective in addressing loneliness, depression, anxiety, and health-related quality of life among a diverse population of adults with loneliness. Moreover, it holds promise as a tool for identifying and referring members to relevant behavioral health resources.

PMID:37930770 | DOI:10.2196/48864

J Clin Endocrinol Metab. 2023 Nov 1:dgad648. doi: 10.1210/clinem/dgad648. Online ahead of print.

ABSTRACT

CONTEXT: Congenital hyperinsulinism (CHI) is characterised by dysregulated insulin secretion causing hypoglycaemia and consequent brain damage. Dasiglucagon is a glucagon analogue under investigation to treat CHI.

OBJECTIVE: To evaluate the efficacy and safety of dasiglucagon delivered via continuous subcutaneous infusion to children with CHI and persistent hypoglycaemia as add-on to standard of care (SoC).

METHODS: In this open-label trial, patients were randomized 1:1 to SoC or SoC + dasiglucagon (10-70 µg/hour) for 4 weeks. In the following 4 weeks, all patients received dasiglucagon + SoC. Hypoglycaemia was assessed by self-monitored plasma glucose (SMPG) and blinded continuous glucose monitoring (CGM). Primary endpoint was average number of SMPG-detected hypoglycaemia episodes/week (SMPG <3.9 mmol/L) during Weeks 2-4.

RESULTS: Thirty-two patients (0.6-10.9 years) were randomly assigned to dasiglucagon + SoC (n=16) or SoC (n=16). The rate of SMPG-detected hypoglycaemia decreased from baseline in both groups, but with no statistically significant difference during Weeks 2-4 (event rate ratio: 0.85 [0.54; 1.36], p=0.5028). However, dasiglucagon administration resulted in a 43% reduction in CGM-detected hypoglycaemia (<3.9 mmol/L) vs. SoC alone during Weeks 2-4 (post-hoc analysis; event rate ratio: 0.57 [0.39; 0.83], p=0.0029). Dasiglucagon enabled reductions (of 37-61%) in all other measures of hypoglycaemia assessed by CGM vs. SoC alone including extent and %-time in hypoglycaemia (post-hoc analyses). Dasiglucagon appeared safe and well tolerated. Skin and gastrointestinal events were more frequent with dasiglucagon + SoC than SoC only.

CONCLUSION: Clinically meaningful reductions in all CGM-recorded measures of hypoglycaemia support using dasiglucagon as a potential treatment for CHI.

PMID:37930757 | DOI:10.1210/clinem/dgad648

Nephrol Dial Transplant. 2023 Oct 31:gfad223. doi: 10.1093/ndt/gfad223. Online ahead of print.

ABSTRACT

BACKGROUND AND HYPOTHESIS: The risk of Diabetic Kidney Disease (DKD) progression is significant despite renin-angiotensin system (RAS) blocking agents treatment. Current clinical tools cannot predict whether or not patients will respond to the treatment with RAS-inhibitors (RASi). We aimed to investigate if proteome analysis could identify urinary peptides as biomarkers that could predict the response to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARBs) treatment to avoid DKD progression. Furthermore, we investigated the comparability of the estimated glomerular filtration rate (eGFR), calculated using four different GFR-equations, for DKD progression.

METHODS: We evaluated urine samples from a discovery cohort of 199 diabetic patients treated with RASi. DKD progression was defined based on eGFR percentage slope results between visits (∼1 year) and for the entire period (∼3 year) based on the eGFR values of each GFR-equation. Urine samples were analysed using capillary electrophoresis coupled mass spectrometry. Statistical analysis was performed between the uncontrolled (patients who did not respond to RASi treatment) and controlled kidney function groups (patients who responded to the RASi treatment). Peptides were combined in a support vector machine-based model. The area under the receiver operating characteristic curve (AUC) was used to evaluate the risk prediction models in two independent validation cohorts treated with RASi.

RESULTS: The classification of patients into uncontrolled and controlled kidney function varies depending on the GFR-equation used, despite the same sample set. We identified 227 peptides showing nominal significant difference and consistent fold changes between uncontrolled and controlled patients in at least three methods of eGFR calculation. These included fragments of collagens, alpha-1-antitrypsin, antithrombin-III, CD99 antigen, and uromodulin. A model based on 189 of 227 peptides (DKDp189) showed a significant prediction of non-response to the treatment/DKD progression in two independent cohorts.

CONCLUSIONS: The DKDp189 model demonstrates potential as a predictive tool for guiding treatment with RASi in diabetic patients.

PMID:37930730 | DOI:10.1093/ndt/gfad223

Telemed J E Health. 2023 Nov 6. doi: 10.1089/tmj.2023.0155. Online ahead of print.

ABSTRACT

Introduction: Image quality and acquisition protocol adherence assessment is a neglected area in teledermatology. We examine if it is feasible to use deep learning methods to automate the assessment of the adherence of examinations to image acquisition protocols. In this study, we focused on the quality criteria of two image acquisition protocols: (1) approximation image and (2) panoramic image, as these are present in all teledermatology examination protocols currently used by the Santa Catarina State Integrated Telemedicine and Telehealth System (STT/SC). Methods: We use a data set of 36,102 teledermatological examinations performed at the STT/SC during 2021. As our validation process, we adopted standard machine learning metrics and an inter-rater agreement (IRA) study with 11 dermatologists. For the approximation image protocol, we used the Mask-Region based Convolutional Neural Network (RCNN) Object Detection Deep Learning (DL) architecture to identify the presence of a lesion identification tag and a ruler used to provide a frame reference of the lesion. For the panoramic image protocol, we used DensePose, a pose estimation DL, architecture to assess the presence of a whole patient body and its orientation. A combination of the two approaches was additionally validated through an IRA study between specialists. Results: Mask-RCNN achieved a score of 96% mean average precision (mAP), while DensePose presented 75% mAP. IRA achieved a level of agreement of 96.68% with the Krippendorff alpha score. Conclusions: Our results show the feasibility of using deep learning to automate the image quality and protocol adherence assessment in teledermatology, before the specialist’s manual analysis of the examination.

PMID:37930716 | DOI:10.1089/tmj.2023.0155

JAMA Neurol. 2023 Nov 6. doi: 10.1001/jamaneurol.2023.3599. Online ahead of print.

ABSTRACT

IMPORTANCE: Apolipoprotein E (APOE)*2 and APOE*4 are, respectively, the strongest protective and risk-increasing, common genetic variants for late-onset Alzheimer disease (AD), making APOE status highly relevant toward clinical trial design and AD research broadly. The associations of APOE genotypes with AD are modulated by age, sex, race and ethnicity, and ancestry, but these associations remain unclear, particularly among racial and ethnic groups understudied in the AD and genetics research fields.

OBJECTIVE: To assess the stratified associations of APOE genotypes with AD risk across sex, age, race and ethnicity, and global population ancestry.

DESIGN, SETTING, PARTICIPANTS: This genetic association study included case-control, family-based, population-based, and longitudinal AD-related cohorts that recruited referred and volunteer participants. Data were analyzed between March 2022 and April 2023. Genetic data were available from high-density, single-nucleotide variant microarrays, exome microarrays, and whole-exome and whole-genome sequencing. Summary statistics were ascertained from published AD genetic studies.

MAIN OUTCOMES AND MEASURES: The main outcomes were risk for AD (odds ratios [ORs]) and risk of conversion to AD (hazard ratios [HRs]), with 95% CIs. Risk for AD was evaluated through case-control logistic regression analyses. Risk of conversion to AD was evaluated through Cox proportional hazards regression survival analyses.

RESULTS: Among 68 756 unique individuals, analyses included 21 852 East Asian (demographic data not available), 5738 Hispanic (68.2% female; mean [SD] age, 75.4 [8.8] years), 7145 non-Hispanic Black (hereafter referred to as Black) (70.8% female; mean [SD] age, 78.4 [8.2] years), and 34 021 non-Hispanic White (hereafter referred to as White) (59.3% female; mean [SD] age, 77.0 [9.1] years) individuals. There was a general, stepwise pattern of ORs for APOE*4 genotypes and AD risk across race and ethnicity groups. Odds ratios for APOE*34 and AD risk attenuated following East Asian (OR, 4.54; 95% CI, 3.99-5.17),White (OR, 3.46; 95% CI, 3.27-3.65), Black (OR, 2.18; 95% CI, 1.90-2.49) and Hispanic (OR, 1.90; 95% CI, 1.65-2.18) individuals. Similarly, ORs for APOE*22+23 and AD risk attenuated following White (OR, 0.53, 95% CI, 0.48-0.58), Black (OR, 0.69, 95% CI, 0.57-0.84), and Hispanic (OR, 0.89; 95% CI, 0.72-1.10) individuals, with no association for Hispanic individuals. Deviating from the global pattern of ORs, APOE*22+23 was not associated with AD risk in East Asian individuals (OR, 0.97; 95% CI, 0.77-1.23). Global population ancestry could not explain why Hispanic individuals showed APOE associations with less pronounced AD risk compared with Black and White individuals. Within Black individuals, decreased global African ancestry or increased global European ancestry showed a pattern of APOE*4 dosage associated with increasing AD risk, but no such pattern was apparent for APOE*2 dosage with AD risk. The sex-by-age-specific interaction effect of APOE*34 among White individuals (higher risk in women) was reproduced but shifted to ages 60 to 70 years (OR, 1.48; 95% CI, 1.10-2.01) and was additionally replicated in a meta-analysis of Black individuals and Hispanic individuals (OR, 1.72; 95% CI, 1.01-2.94).

CONCLUSION AND RELEVANCE: Through recent advances in AD-related genetic cohorts, this study provided the largest-to-date overview of the association of APOE with AD risk across age, sex, race and ethnicity, and population ancestry. These novel insights are critical to guide AD clinical trial design and research.

PMID:37930705 | DOI:10.1001/jamaneurol.2023.3599

JAMA Netw Open. 2023 Nov 1;6(11):e2341422. doi: 10.1001/jamanetworkopen.2023.41422.

ABSTRACT

IMPORTANCE: Although hospice care has been covered by health insurance for the purpose of improving the quality of life of patients with terminal cancer as well as their caregivers, few studies have evaluated the outcomes of the policy to cover home-based hospice care services.

OBJECTIVE: To investigate the changes in the place of death of patients with cancer after the introduction of insurance-covered, home-based hospice care services in Korea.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from February 1, 2018, to December 31, 2021, from the Causes of Death Statistics database, released annually by Statistics Korea, which contains information on all deaths in the country. Individuals who died of cancer, a representative hospice-eligible disease, were assigned to the case group, and those who died of dementia, a non-hospice-eligible disease, were assigned to the control group. A total of 218 522 individuals constituted the study population.

EXPOSURE: Because the Korean Health Insurance Service had begun covering home-based hospice care services on September 1, 2020, and the last follow-up date was December 31, 2021, the follow-up periods for before and after intervention were 31 months and 16 months, respectively (preintervention period: February 1, 2018, to August 31, 2020; postintervention period: September 1, 2020 to December 31, 2021).

MAIN OUTCOMES AND MEASURES: The place of death was categorized as a binary variable according to whether it was the person’s own home or not. Comparative interrupted time-series models with segmented regression were applied to analyze the time trend and its change in outcomes.

RESULTS: Of the 218 522 deaths eligible for the analysis (mean [SD] age at death, 78.6 [8.8] years; 130 435 men [59.7%]), 207 459 were due to cancer, and 11 063 were due to dementia. Immediately after the introduction of home-based hospice care, the rate of home deaths was 24.5% higher for patients with cancer than for those with dementia (estimate, 1.245 [95% CI, 1.030-1.504]; P = .02). The difference in the level change between cancer deaths and dementia deaths, on intervention, was more pronounced for those living in rural areas (estimate, 1.320 [95% CI, 1.118-1.558]; P = .001). In addition, a higher educational level was associated with a larger difference in the immediate effect size due to home-based hospice care (low educational level: estimate, 1.205 [95% CI, 1.025-1.416]; P = .02; middle educational level: estimate, 1.307 [95% CI, 0.987-1.730], P = .06; high educational level: estimate, 1.716 [95% CI, 0.932-3.159]; P = .08).

CONCLUSIONS AND RELEVANCE: In this cohort study exploring the changes in the place of death for patients with cancer after the insurance mandates for home-based hospice care in Korea, the probability of patients with cancer dying in their own homes increased after the intervention. This finding suggests the need to broaden the extent of home-based hospice care to honor the autonomy of individuals with terminal illness and improve their quality of death.

PMID:37930703 | DOI:10.1001/jamanetworkopen.2023.41422

JAMA Netw Open. 2023 Nov 1;6(11):e2341516. doi: 10.1001/jamanetworkopen.2023.41516.

ABSTRACT

IMPORTANCE: To date, the diagnostic test completion rate and the time to diagnostic endoscopy or colonoscopy among adults with iron-deficiency anemia (IDA) and/or hematochezia have not been well characterized.

OBJECTIVE: To evaluate the diagnostic test completion rate and the time to diagnostic testing among veterans younger than 50 years with IDA and/or hematochezia.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted within the Veterans Health Administration between October 1, 1999, and December 31, 2019, among US veterans aged 18 to 49 years from 2 separate cohorts: those with a diagnosis of IDA (n = 59 169) and those with a diagnosis of hematochezia (n = 189 185). Statistical analysis was conducted from August 2021 to August 2023.

EXPOSURES: Diagnostic testing factors included age, sex, race and ethnicity, Veterans Health Administration geographic region, and hemoglobin test value (IDA cohort only).

MAIN OUTCOMES AND MEASURES: Primary outcomes of diagnostic testing were (1) bidirectional endoscopy after diagnosis of IDA and (2) colonoscopy or sigmoidoscopy after diagnosis of hematochezia. The association between diagnostic testing factors and diagnostic test completion was examined using Poisson models.

RESULTS: There were 59 169 veterans with a diagnosis of IDA (mean [SD] age, 40.7 [7.1] years; 30 502 men [51.6%]), 189 185 veterans with a diagnosis of hematochezia (mean [SD] age, 39.4 [7.6] years; 163 690 men [86.5%]), and 2287 veterans with IDA and hematochezia (mean [SD] age, 41.6 [6.9] years; 1856 men [81.2%]). The cumulative 2-year diagnostic workup completion rate was 22% (95% CI, 22%-22%) among veterans with IDA and 40% (95% CI, 40%-40%) among veterans with hematochezia. Veterans with IDA were mostly aged 40 to 49 years (37 719 [63.7%]) and disproportionately Black (24 480 [41.4%]). Women with IDA (rate ratio [RR], 0.42; 95% CI, 0.40-0.43) had a lower likelihood of diagnostic test completion compared with men with IDA. Black (RR, 0.65; 95% CI, 0.62-0.68) and Hispanic (RR, 0.88; 95% CI, 0.82-0.94) veterans with IDA were less likely to receive diagnostic testing compared with White veterans with IDA. Veterans with hematochezia were mostly White (105 341 [55.7%]). Among veterans with hematochezia, those aged 30 to 49 years were more likely to receive diagnostic testing than adults younger than 30 years of age (age 30-39 years: RR, 1.15; 95% CI, 1.12-1.18; age 40-49 years: RR, 1.36; 95% CI, 1.33-1.40). Hispanic veterans with hematochezia were less likely to receive diagnostic testing compared with White veterans with hematochezia (RR, 0.96; 95% CI, 0.93-0.98).

CONCLUSIONS AND RELEVANCE: In the cohorts of veterans younger than 50 years with IDA and/or hematochezia, the diagnostic test completion rate was low. Follow-up was less likely among female, Black, and Hispanic veterans with IDA and Hispanic veterans with hematochezia. Optimizing timely follow-up across social and demographic groups may contribute to improving colorectal cancer outcomes and mitigate disparities.

PMID:37930701 | DOI:10.1001/jamanetworkopen.2023.41516

J Womens Health (Larchmt). 2023 Nov 6. doi: 10.1089/jwh.2023.0307. Online ahead of print.

ABSTRACT

Background: We previously examined National Institutes of Health (NIH)-funded randomized controlled trials (RCTs) published in 2004, 2009, and 2015 and found low compliance with NIH policies on inclusion, analysis, and reporting results for female and minoritized subgroups, with no improvement over time. We conducted a fourth wave of data collection using RCTs published in 2021, comparing current results with previous years. Materials and Methods: The authors used PubMed to find 657 RCTs published in print in 14 leading US medical journals in 2021. Of those, 93 (14.2%) were eligible for analysis. We reviewed all parts of eligible studies and any published commentary. Fisher’s exact statistics compared proportions of studies analyzing or reporting results for subgroups in 2021 compared with RCTs studied in previous waves. Posthoc analysis compared eligible RCTs about the Covid-19 pandemic to eligible RCTs on other topics. Results: Twenty-five of 93 studies (26.9%) analyzed or reported outcomes by race or ethnicity, an increase over previous years (p < 0.01). Among 79 RCTs with participants of both sexes, the median proportion of female participants was 43%. Moreover, 34 (43.0%) reported an outcome by sex, included sex as a covariate in statistical analysis, or reported results by sex, also an increase over previous waves (p < 0.01). Eleven eligible studies (11.8%) were on a SARS-CoV-2 topic; there was no difference between SARS-CoV-2 RCTs and RCTs on other topics. Conclusions: Analysis and reporting by sex, race, and ethnicity for NIH-funded RCTs published in 2021 significantly increased from previous waves, despite no corresponding increase in enrollment.

PMID:37930690 | DOI:10.1089/jwh.2023.0307