Category: Nevin Manimala

J Med Internet Res. 2023 Dec 6;25:e48145. doi: 10.2196/48145.

ABSTRACT

BACKGROUND: Electronic health records (EHRs) in unstructured formats are valuable sources of information for research in both the clinical and biomedical domains. However, before such records can be used for research purposes, sensitive health information (SHI) must be removed in several cases to protect patient privacy. Rule-based and machine learning-based methods have been shown to be effective in deidentification. However, very few studies investigated the combination of transformer-based language models and rules.

OBJECTIVE: The objective of this study is to develop a hybrid deidentification pipeline for Australian EHR text notes using rules and transformers. The study also aims to investigate the impact of pretrained word embedding and transformer-based language models.

METHODS: In this study, we present a hybrid deidentification pipeline called OpenDeID, which is developed using an Australian multicenter EHR-based corpus called OpenDeID Corpus. The OpenDeID corpus consists of 2100 pathology reports with 38,414 SHI entities from 1833 patients. The OpenDeID pipeline incorporates a hybrid approach of associative rules, supervised deep learning, and pretrained language models.

RESULTS: The OpenDeID achieved a best F₁-score of 0.9659 by fine-tuning the Discharge Summary BioBERT model and incorporating various preprocessing and postprocessing rules. The OpenDeID pipeline has been deployed at a large tertiary teaching hospital and has processed over 8000 unstructured EHR text notes in real time.

CONCLUSIONS: The OpenDeID pipeline is a hybrid deidentification pipeline to deidentify SHI entities in unstructured EHR text notes. The pipeline has been evaluated on a large multicenter corpus. External validation will be undertaken as part of our future work to evaluate the effectiveness of the OpenDeID pipeline.

PMID:38055317 | DOI:10.2196/48145

JMIR Form Res. 2023 Dec 6;7:e47630. doi: 10.2196/47630.

ABSTRACT

BACKGROUND: Adolescents with disabilities experience alarmingly higher rates of depression and isolation than peers without disabilities. There is a need to identify interventions that can improve mental health and isolation among this underserved population. Innovations in virtual reality (VR) gaming “standalone” headsets allow greater access to immersive high-quality digital experiences, due to their relatively low cost.

OBJECTIVE: This study had three purposes, which were to (1) examine the preliminary effects of a low-cost, home-based VR multiplayer recreation and socialization on depression, socialization, and loneliness; (2) quantify the acceptability of the program as measured by participant adherence, total play time, and exercise time; and (3) identify and describe behavioral mechanisms that affected participant engagement.

METHODS: This was a single-group, pre- to postdesign trial. The intervention was conducted at home. Participants were recruited from a children’s hospital. The intervention lasted 4 weeks and included 2×1-hour sessions per week of supervised peer-to-peer gaming. Participants used the Meta Quest 2 headset to meet peers and 2 coaches in a private party held digitally. Aim 1 was evaluated with the Children’s Depression Inventory 2 Short Form and the University of California, Los Angeles Loneliness Scale 20 items, which are measures of social isolation and loneliness, respectively. Aim 2 was evaluated through the following metrics: participant adherence, the types of games played, friendship building and playtime, and program satisfaction and enjoyment.

RESULTS: In total, 12 people enrolled (mean age 16.6, SD 1.8 years; male: n=9 and female: n=3), and 8 people completed the program. Mean attendance for the 8 participants was 77% (49 sessions of 64 total possible sessions; mean 6, SD 2 sessions). A trend was observed for improved Children’s Depression Inventory 2 Short Form scores (mean preintervention score 7.25, SD 4.2; mean postintervention score 5.38, SD 4.1; P=.06; effect size=0.45, 95% CI -0.15 to 3.9), but this was not statistically significant; no difference was observed for University of California, Los Angeles Loneliness Scale 20 items scores. Most participants (7/8, 88%) stated that they became friends with a peer in class; 50% (4/8) reported that they played with other people. Participants reported high levels of enjoyment and satisfaction with how the program was implemented. Qualitative analysis resulted in 4 qualitative themes that explained behavioral mechanisms that determined engagement in the program.

CONCLUSIONS: The study findings demonstrated that a brief VR group program could be valuable for potentially improving mental health among adolescents with physical disabilities. Participants built friendships with peers and other players on the web, using low-cost consumer equipment that provided easy access and strong scale-up potential. Study findings identified factors that can be addressed to enhance the program within a larger clinical trial.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05259462; https://clinicaltrials.gov/study/NCT05259462.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/42651.

PMID:38055309 | DOI:10.2196/47630

J Acquir Immune Defic Syndr. 2024 Jan 1;95(1):65-73. doi: 10.1097/QAI.0000000000003312.

ABSTRACT

BACKGROUND: Pregnancy represents a period of high HIV acquisition risk. Safety data for the monthly dapivirine vaginal ring (DVR) during pregnancy are limited. Here, we report data from the first 2 cohorts of pregnant participants in MTN-042/DELIVER, a phase 3b, randomized, open-label safety trial of DVR and oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). MTN-042 is being conducted in 3 cohorts beginning with later gestational ages when risks of drug exposure are less.

METHODS: Eligible pregnant individuals aged 18-40 years in Malawi, South Africa, Uganda, and Zimbabwe were randomized 2:1 to monthly DVR or daily TDF/FTC. Participants in cohort 1 initiated product use between 36 weeks 0 days (36 0/7 weeks) and 37 6/7 weeks gestation; participants in cohort 2 initiated product use between 30 0/7 and 35 6/7 weeks gestation. All participants continued product use until delivery or 41 6/7 weeks gestation. Pregnancy outcomes and complications were assessed and summarized using descriptive statistics and compared with local background rates obtained through a separate chart review.

RESULTS: One-hundred and fifty participants were enrolled into cohort 1 with 101 randomized to DVR and 49 to TDF/FTC. One-hundred and fifty-seven participants were enrolled into cohort 2 with 106 randomized to DVR and 51 to TDF/FTC. In both cohorts, pregnancy complications were rare and similar to local background rates.

CONCLUSION: In this first study of a long-acting HIV prevention agent in pregnancy, adverse pregnancy outcomes and complications were uncommon when DVR and TDF/FTC were used in the third trimester of pregnancy, suggesting a favorable safety profile for both prevention products.

PMID:38055292 | DOI:10.1097/QAI.0000000000003312

Cancer. 2023 Dec 6. doi: 10.1002/cncr.35130. Online ahead of print.

ABSTRACT

BACKGROUND: Although the associations between genetic variations and lung cancer risk have been explored, the epigenetic consequences of DNA methylation in lung cancer development are largely unknown. Here, the genetically predicted DNA methylation markers associated with non-small cell lung cancer (NSCLC) risk by a two-stage case-control design were investigated.

METHODS: The genetic prediction models for methylation levels based on genetic and methylation data of 1595 subjects from the Framingham Heart Study were established. The prediction models were applied to a fixed-effect meta-analysis of screening data sets with 27,120 NSCLC cases and 27,355 controls to identify the methylation markers, which were then replicated in independent data sets with 7844 lung cancer cases and 421,224 controls. Also performed was a multi-omics functional annotation for the identified CpGs by integrating genomics, epigenomics, and transcriptomics and investigation of the potential regulation pathways.

RESULTS: Of the 29,894 CpG sites passing the quality control, 39 CpGs associated with NSCLC risk (Bonferroni-corrected p ≤ 1.67 × 10^-6 ) were originally identified. Of these, 16 CpGs remained significant in the validation stage (Bonferroni-corrected p ≤ 1.28 × 10^-3 ), including four novel CpGs. Multi-omics functional annotation showed nine of 16 CpGs were potentially functional biomarkers for NSCLC risk. Thirty-five genes within a 1-Mb window of 12 CpGs that might be involved in regulatory pathways of NSCLC risk were identified.

CONCLUSIONS: Sixteen promising DNA methylation markers associated with NSCLC were identified. Changes of the methylation level at these CpGs might influence the development of NSCLC by regulating the expression of genes nearby.

PLAIN LANGUAGE SUMMARY: The epigenetic consequences of DNA methylation in lung cancer development are still largely unknown. This study used summary data of large-scale genome-wide association studies to investigate the associations between genetically predicted levels of methylation biomarkers and non-small cell lung cancer risk at the first time. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. These findings will provide a unique insight into the epigenetic susceptibility mechanisms of lung cancer.

PMID:38055287 | DOI:10.1002/cncr.35130

JAMA Surg. 2023 Dec 6. doi: 10.1001/jamasurg.2023.6254. Online ahead of print.

ABSTRACT

IMPORTANCE: A standardized definition and reporting of metabolic bariatric surgery (MBS) outcomes is not available for actual clinical practice and science.

OBJECTIVE: To assess the feasibility of using a clinically relevant and feasible MBS outcome score (Swiss-Finnish Bariatric Metabolic Outcome Score [SF-BARI Score]).

DESIGN, SETTING, AND PARTICIPANTS: This assessment of a bariatric surgery outcome score is based on the secondary analysis of merged 5-year individual patient data (N = 457) of 2 large randomized clinical trials (Swiss SM-BOSS [Swiss Multicenter Bypass or Sleeve Study], conducted from January 2007 to November 2011, and Finnish SLEEVEPASS [Laparoscopic Gastric Bypass Vs Sleeve Gastrectomy to Treat Morbid Obesity], conducted from March 2008 until June 2010) that compared laparoscopic sleeve gastrectomy with laparoscopic Roux-en-Y gastric bypass in the treatment of severe obesity. This secondary analysis was performed from January 2022 to January 2023.

MAIN OUTCOMES AND MEASURES: The main outcome was the feasibility of the SF-BARI Score and the SF-BARI Score QOL (quality of life) as tools to assess MBS outcomes. The score includes percentage of total weight loss (%TWL), 4 obesity-related comorbidities (type 2 diabetes, hypertension, dyslipidemia, and obstructive sleep apnea), complications, and QOL, if available.

RESULTS: Among the 457 included patients, 323 (70.7%) were female and 134 (29.3%) were male, and the mean (SD) age was 45.6 (10.7) years. Outcomes for the SF-BARI Score were available for 435 patients (95.2%) at 1 year and 398 patients (87.1%) at 5 years and for SF-BARI Score QOL in 289 (63.2%) patients at 1 year and 318 patients (69.6%) at 5 years. The SF-BARI Score was correlated with both the SF-BARI Score QOL (r = 0.96; 95% CI, 0.95-0.96; P < .001) and %TWL (r = 0.86; 95% CI, 0.84-0.89; P < .001) and with the Bariatric Analysis and Reporting Outcome System (r = 0.59; 95% CI, 0.51-0.65; P < .001). Score outcomes were categorized as excellent, very good, good, fair, and suboptimal response. There was a statistically significant difference in scores at 1 vs 5 years (4.0; 95% CI, 1.4-6.6; P = .003), and the gastric bypass group had a higher score compared with the sleeve gastrectomy group (7.4; 95% CI, 3.4-11.5; P < .001).

CONCLUSIONS AND RELEVANCE: These findings indicate that this metabolic bariatric surgery outcome score is a simple, relevant, and feasible composite tool to define and measure MBS outcomes, enabling standardized reporting.

TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT00356213 (SM-BOSS) and NCT00793143 (SLEEVEPASS).

PMID:38055284 | DOI:10.1001/jamasurg.2023.6254

JAMA Netw Open. 2023 Dec 1;6(12):e2334757. doi: 10.1001/jamanetworkopen.2023.34757.

ABSTRACT

IMPORTANCE: Incidence of colorectal cancer (CRC) is increasing among younger adults. However, data on precursor lesions in patients who are asymptomatic, especially those aged younger than 50 years, are lacking.

OBJECTIVE: To analyze the prevalence and number needed to screen (NNS) for adenomas, advanced adenomas, and serrated lesions, as well as the incidence of CRC in patients older than age 20 years.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted among 296 170 patients who received a screening colonoscopy within a national screening colonoscopy registry from 2012 to 2018 in Austria, including 11 103 patients aged younger than 50 years. CRC incidence was analyzed using data from Statistic Austria from 1988 to 2018. Data were analyzed in September 2021.

MAIN OUTCOME AND MEASURES: The prevalence of adenomas and other lesions and the incidence of CRC in individuals aged 20 years or older were assessed.

RESULTS: Among 296 170 patients included in the study (median [IQR] age, 60 [54-68] years; 150 813 females [50.9%]), 11 103 patients (3.7%) were aged younger than 50 years and 285 067 patients (96.3%) were aged 50 years or older. Among patients younger than age 50 years, 1166 individuals (10.5%; NNS = 9) had adenomas and 389 individuals (3.9%; NNS = 26) had at least 1 advanced adenoma, while among those aged 50 years or older, 62 384 individuals (21.9%; NNS = 5) had adenomas and 19 680 individuals (6.9%; NNS = 15) had at least 1 advanced adenoma. Among 1128 males aged 40 to 44 years, 160 individuals (14.2%; NNS = 7) had at least 1 adenoma, and among 1398 females aged 40 to 44 years, 114 individuals (8.1%; NNS = 12) had at least 1 adenoma. The prevalence of adenomas for individuals aged 45 to 49 years vs 50 to 54 years was 490 of 2879 males (17.1%; NNS = 6) vs 8269 of 40 935 males (20.2%; NNS = 5) and 284 of 2792 females (10.2%; NNS = 10) vs 4997 of 40 303 females (12.4%; NNS = 8), respectively. Prevalence of adenomas changed from 61 of 498 individuals (12.4%) in 2008 to 150 of 1064 individuals (14.1%) in 2018 among those younger than 50 years and from 2646 of 12 166 individuals (21.8%) to 10 673 of 37 922 individuals (28.2%) among those aged 50 years and older. The prevalence of advanced adenomas changed from 20 individuals (4.0%) in 2008 to 55 individuals (5.2%) in 2018 in individuals younger than 50 years and from 888 individuals (7.3%) in 2008 to 2578 individuals (6.8%) in 2018 among those aged 50 years and older. Among individuals younger than age 50 years, CRC incidence per 100 000 individuals changed from 9.1 incidents in 1988 to 10.2 incidents in 2018 among males (average annual percentage change [AAPC], 0.5%; 95% CI, 0.1% to 1.0%) and from 9.7 incidents in 1988 to 7.7 incidents in 2018 among females, with a nonsignificant AAPC (-0.2%; 95% CI, -0.7% to 0.3%). Among individuals aged 50 years or older, CRC incidence per 100 000 individuals changed from 168 incidents in 1988 to 97 incidents in 2018 among females (AAPC, -1.8%; 95% CI, -1.9% to -1.6%), and 217 incidents in 1988 to 143 incidents in 2018 among males (AAPC, -1.2%; 95% CI, -1.3% to -1.1%).

CONCLUSION: In this study, CRC incidence decreased after 1988 in Austria among individuals older than 50 years, while among patients younger than 50 years, incidence increased among males but decreased among females. Prevalence of adenomas increased in all age groups, while advanced adenoma prevalence increased among patients younger than 50 years but decreased in patients aged 50 years and older.

PMID:38055281 | DOI:10.1001/jamanetworkopen.2023.34757

JAMA Netw Open. 2023 Dec 1;6(12):e2346113. doi: 10.1001/jamanetworkopen.2023.46113.

ABSTRACT

IMPORTANCE: Postpancreatectomy hemorrhage (PPH) due to postoperative pancreatic fistula (POPF) is a life-threatening complication after pancreatoduodenectomy. However, there is no prediction tool for early identification of patients at high risk of late PPH.

OBJECTIVE: To develop and validate a prediction model for PPH.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective prognostic study included consecutive patients with clinically relevant POPF who underwent pancreatoduodenectomy from January 1, 2009, to May 20, 2023, at the University Hospital Mannheim (derivation cohort), and from January 1, 2012, to May 31, 2022, at the University Hospital Dresden (validation cohort). Data analysis was performed from May 30 to July 29, 2023.

EXPOSURE: Clinical and radiologic features of PPH.

MAIN OUTCOMES AND MEASURES: Accuracy of a predictive risk score of PPH. A multivariate prediction model-the hemorrhage risk score (HRS)-was established in the derivation cohort (n = 139) and validated in the validation cohort (n = 154).

RESULTS: A total of 293 patients (187 [64%] men; median age, 69 [IQR, 60-76] years) were included. The HRS comprised 4 variables with associations: sentinel bleeding (odds ratio [OR], 35.10; 95% CI, 5.58-221.00; P < .001), drain fluid culture positive for Candida species (OR, 14.40; 95% CI, 2.24-92.20; P < .001), and radiologic proof of rim enhancement of (OR, 12.00; 95% CI, 2.08-69.50; P = .006) or gas within (OR, 12.10; 95% CI, 2.22-65.50; P = .004) a peripancreatic fluid collection. Two risk categories were identified with patients at low risk (0-1 points) and high risk (≥2 points) to develop PPH. Patients with PPH were predicted accurately in the derivation cohort (C index, 0.97) and validation cohort (C index 0.83). The need for more invasive PPH management (74% vs 34%; P < .001) and severe complications (49% vs 23%; P < .001) were more frequent in high-risk patients compared with low-risk patients.

CONCLUSIONS AND RELEVANCE: In this retrospective prognostic study, a robust prediction model for PPH was developed and validated. This tool may facilitate early identification of patients at high risk for PPH.

PMID:38055279 | DOI:10.1001/jamanetworkopen.2023.46113

JAMA Netw Open. 2023 Dec 1;6(12):e2346323. doi: 10.1001/jamanetworkopen.2023.46323.

ABSTRACT

IMPORTANCE: Adverse childhood experiences (ACEs) are preventable, potentially traumatic events in childhood, such as experiencing abuse or neglect, witnessing violence, or living in a household with substance use disorder, mental health problems, or instability from parental separation or incarceration. Adults who had ACEs have more harmful risk behaviors and worse health outcomes; the economic burden associated with these issues is uncertain.

OBJECTIVE: To estimate the economic burden of ACE-associated health conditions among US adults.

DESIGN, SETTING, AND PARTICIPANTS: In this economic evaluation, regression models of cross-sectional survey data from the 2019-2020 Behavioral Risk Factor Surveillance System (BRFSS) and previous studies were used to estimate ACE population-attributable fractions (PAFs) (ie, the fraction of total cases associated with a specific exposure) for selected health outcomes (anxiety, arthritis, asthma, cancer, chronic obstructive pulmonary disease, depression, diabetes, heart disease, kidney disease, stroke, and violence) and risk factors (heavy drinking, illicit drug use, overweight and obesity, and smoking) among the 2019 US adult population. Adverse childhood experience PAFs were used to calculate the proportion of total condition-specific medical spending and lost healthy life-years related to ACEs using Global Burden of Disease Study data. Data analysis was performed from September 10, 2021, to November 29, 2022.

EXPOSURE: Adverse childhood experiences (age <18 years).

MAIN OUTCOMES AND MEASURES: Monetary valuation of ACE-associated morbidity and mortality using standard US value of statistical life methods and presented in terms of annual and lifetime per affected person and total population estimates at the national and state levels.

RESULTS: A total of 820 673 adults, representing 255 million individuals, participated in the BRFSS in 2019 and 2020. An estimated 160 million of the total 255 million US adult population (63%) had 1 or more ACE, associated with an annual economic burden of $14.1 trillion ($183 billion in direct medical spending and $13.9 trillion in lost healthy life-years). This was $88 000 per affected adult annually and $2.4 million over their lifetimes. The lifetime economic burden per affected adult was lowest in North Dakota ($1.3 million) and highest in Arkansas ($4.3 million). Twenty-two percent of adults had 4 or more ACEs and comprised 58% of the total economic burden-the estimated per person lifetime economic burden for those adults was $4.0 million.

CONCLUSIONS AND RELEVANCE: In this cross-sectional analysis of the US adult population, the economic burden of ACE-related health conditions was substantial. The findings suggest that measuring the economic burden of ACEs can support decision-making about investing in strategies to improve population health.

PMID:38055277 | DOI:10.1001/jamanetworkopen.2023.46323

JAMA Psychiatry. 2023 Dec 6. doi: 10.1001/jamapsychiatry.2023.4313. Online ahead of print.

NO ABSTRACT

PMID:38055275 | DOI:10.1001/jamapsychiatry.2023.4313

JAMA Cardiol. 2023 Dec 6. doi: 10.1001/jamacardio.2023.4520. Online ahead of print.

ABSTRACT

IMPORTANCE: Use of race-specific risk prediction in clinical medicine is being questioned. Yet, the most commonly used prediction tool for atherosclerotic cardiovascular disease (ASCVD)-pooled cohort risk equations (PCEs)-uses race stratification.

OBJECTIVE: To quantify the incremental value of race-specific PCEs and determine whether adding social determinants of health (SDOH) instead of race improves model performance.

DESIGN, SETTING, AND PARTICIPANTS: Included in this analysis were participants from the biracial Reasons for Geographic and Racial Differences in Stroke (REGARDS) prospective cohort study. Participants were aged 45 to 79 years, without ASCVD, and with low-density lipoprotein cholesterol level of 70 to 189 mg/dL or non-high-density lipoprotein cholesterol level of 100 to 219 mg/dL at baseline during the period of 2003 to 2007. Participants were followed up to 10 years for incident ASCVD, including myocardial infarction, coronary heart disease death, and fatal and nonfatal stroke. Study data were analyzed from July 2022 to February 2023.

MAIN OUTCOME/MEASURES: Discrimination (C statistic, Net Reclassification Index [NRI]), and calibration (plots, Nam D’Agostino test statistic comparing observed to predicted events) were assessed for the original PCE, then for a set of best-fit, race-stratified equations including the same variables as in the PCE (model C), best-fit equations without race stratification (model D), and best-fit equations without race stratification but including SDOH as covariates (model E).

RESULTS: This study included 11 638 participants (mean [SD] age, 61.8 [8.3] years; 6764 female [58.1%]) from the REGARDS cohort. Across all strata (Black female, Black male, White female, and White male participants), C statistics did not change substantively compared with model C (Black female, 0.71; 95% CI, 0.68-0.75; Black male, 0.68; 95% CI, 0.64-0.73; White female, 0.77; 95% CI, 0.74-0.81; White male, 0.68; 95% CI, 0.64-0.71), in model D (Black female, 0.71; 95% CI, 0.67-0.75; Black male, 0.68; 95% CI, 0.63-0.72; White female, 0.76; 95% CI, 0.73-0.80; White male, 0.68; 95% CI, 0.65-0.71), or in model E (Black female, 0.72; 95% CI, 0.68-0.76; Black male, 0.68; 95% CI, 0.64-0.72; White female, 0.77; 95% CI, 0.74-0.80; White male, 0.68; 95% CI, 0.65-0.71). Comparing model D with E using the NRI showed a net percentage decline in the correct assignment to higher risk for male but not female individuals. The Nam D’Agostino test was not significant for all race-sex strata in each model series, indicating good calibration in all groups.

CONCLUSIONS: Results of this cohort study suggest that PCE performed well overall but had poorer performance in both BM and WM participants compared with female participants regardless of race in the REGARDS cohort. Removal of race or the addition of SDOH did not improve model performance in any subgroup.

PMID:38055247 | DOI:10.1001/jamacardio.2023.4520