Nevin Manimala

Neural Comput. 2024 Jul 18:1-27. doi: 10.1162/neco_a_01692. Online ahead of print.

ABSTRACT

Adam-type algorithms have become a preferred choice for optimization in the deep learning setting; however, despite their success, their convergence is still not well understood. To this end, we introduce a unified framework for Adam-type algorithms, termed UAdam. It is equipped with a general form of the second-order moment, which makes it possible to include Adam and its existing and future variants as special cases, such as NAdam, AMSGrad, AdaBound, AdaFom, and Adan. The approach is supported by a rigorous convergence analysis of UAdam in the general nonconvex stochastic setting, showing that UAdam converges to the neighborhood of stationary points with a rate of O(1/T). Furthermore, the size of the neighborhood decreases as the parameter β1 increases. Importantly, our analysis only requires the first-order momentum factor to be close enough to 1, without any restrictions on the second-order momentum factor. Theoretical results also reveal the convergence conditions of vanilla Adam, together with the selection of appropriate hyperparameters. This provides a theoretical guarantee for the analysis, applications, and further developments of the whole general class of Adam-type algorithms. Finally, several numerical experiments are provided to support our theoretical findings.

PMID:39106463 | DOI:10.1162/neco_a_01692

Prehosp Emerg Care. 2024 Aug 6:1-15. doi: 10.1080/10903127.2024.2389551. Online ahead of print.

ABSTRACT

OBJECTIVES: The National Emergency Medical Services Information Services (NEMSIS) provides a robust set of data to evaluate prehospital care. However, a major limitation is that the vast majority of the records lack a definitive outcome. We aimed to evaluate the performance of a recently proposed method (‘MLB’ method) to impute missing end-of-EMS-event outcomes (“dead” or “alive”) for patient care reports in the NEMSIS public research dataset.

METHODS: This study reproduced the recently published method for patient outcome imputation in the NEMSIS database and replicated the results for years 2017 through 2022 (n = 686,075). We performed statistical analyses leveraging an array of established performance metrics for binary classification in the machine learning literature. Evaluation metrics included overall accuracy, true positive rate, true negative rate, balanced accuracy, precision, F1 score, Cohen’s Kappa coefficient, Matthews’ coefficient, Hamming loss, the Jaccard similarity score, and the receiver operating characteristic/area under the curve.

RESULTS: Extended metrics show consistently good imputation performance from year-to-year but reveal weakness in accurately indicating the minority class: e.g., after adjustments for conflicting labels, “dead” prediction accuracy was 77.7% for 2018 and 61.8% over the six-year NEMSIS sub-sample, even though overall accuracy was 98.8%. Slight over-fitting is also present.

CONCLUSIONS: We found that the recently published MLB method produced reasonably good “dead” or “alive” indicators. We recommend reporting of True Positive Rate (“dead” prediction accuracy) and True Negative Rate (“alive” prediction accuracy) when applying the imputation method for analyses of NEMSIS data. More attention by EMS clinicians to complete documentation of target NEMSIS elements can further improve the method’s performance.

PMID:39106451 | DOI:10.1080/10903127.2024.2389551

Retina. 2024 Aug 5. doi: 10.1097/IAE.0000000000004230. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the effects of pupil dilation caused by topical applications of 2.5% phenylephrine and 0.5% tropicamide on retinal microvascularization using optical coherence tomography angiography (OCTA).

METHODS: Healthy children were included in this prospective observational study. Baseline OCTA measurements were taken for all children before dilatation. Then they were randomly divided into two groups, the tropicamide group given 0.5% tropicamide solution and the phenylephrine group given 2.5% phenylephrine solution. After dilation OCTA images were taken for the second time from all children.

RESULTS: The effect of dilation using two different mydriatic agents caused a decrease in mean radial peripapillary capillary density (RPC-VD) and superior RPC-VD (p=0.008 and p=0.001). Remarkably, this reduction due to dilatation was also determined to be caused by the combined effect of both mydriatic agents (p=0.016 and p=0.013). Although phenylephrine showed a slightly greater decrease than tropicamide, the effects of the two mydriatic drugs were not superior to each other (p=0.166 and p=0.167).

CONCLUSION: Dilation with 2.5% phenylephrine or 0.5% tropicamide significantly decreased mean RPC-VD and superior RPC-VD. Although there was no statistically significant difference between the two mydriatic agents, phenylephrine caused a greater reduction than tropicamide. This effect of dilation and phenylephrine on VD should be considered in studies using OCTA and focusing on peripapillary areas.

PMID:39106442 | DOI:10.1097/IAE.0000000000004230

J Med Internet Res. 2024 Aug 6;26:e56316. doi: 10.2196/56316.

ABSTRACT

BACKGROUND: This study demonstrates that digital maturity contributes to strengthened quality and safety performance outcomes in US hospitals. Advanced digital maturity is associated with more digitally enabled work environments with automated flow of data across information systems to enable clinicians and leaders to track quality and safety outcomes. This research illustrates that an advanced digitally enabled workforce is associated with strong safety leadership and culture and better patient health and safety outcomes.

OBJECTIVE: This study aimed to examine the relationship between digital maturity and quality and safety outcomes in US hospitals.

METHODS: The data sources were hospital safety letter grades as well as quality and safety scores on a continuous scale published by The Leapfrog Group. We used the digital maturity level (measured using the Electronic Medical Record Assessment Model [EMRAM]) of 1026 US hospitals. This was a cross-sectional, observational study. Logistic, linear, and Tweedie regression analyses were used to explore the relationships among The Leapfrog Group’s Hospital Safety Grades, individual Leapfrog safety scores, and digital maturity levels classified as advanced or fully developed digital maturity (EMRAM levels 6 and 7) or underdeveloped maturity (EMRAM level 0). Digital maturity was a predictor while controlling for hospital characteristics including teaching status, urban or rural location, hospital size measured by number of beds, whether the hospital was a referral center, and type of hospital ownership as confounding variables. Hospitals were divided into the following 2 groups to compare safety and quality outcomes: hospitals that were digitally advanced and hospitals with underdeveloped digital maturity. Data from The Leapfrog Group’s Hospital Safety Grades report published in spring 2019 were matched to the hospitals with completed EMRAM assessments in 2019. Hospital characteristics such as number of hospital beds were obtained from the CMS database.

RESULTS: The results revealed that the odds of achieving a higher Leapfrog Group Hospital Safety Grade was statistically significantly higher, by 3.25 times, for hospitals with advanced digital maturity (EMRAM maturity of 6 or 7; odds ratio 3.25, 95% CI 2.33-4.55).

CONCLUSIONS: Hospitals with advanced digital maturity had statistically significantly reduced infection rates, reduced adverse events, and improved surgical safety outcomes. The study findings suggest a significant difference in quality and safety outcomes among hospitals with advanced digital maturity compared with hospitals with underdeveloped digital maturity.

PMID:39106100 | DOI:10.2196/56316

Clin Cancer Res. 2024 Aug 6. doi: 10.1158/1078-0432.CCR-24-1215. Online ahead of print.

ABSTRACT

PURPOSE: In radiotherapy (RT) for brain tumors, patient heterogeneity masks treatment effects, complicating the prediction and mitigation of radiation-induced brain necrosis. Therefore, understanding this heterogeneity is essential for improving outcome assessments and reducing toxicity.

EXPERIMENTAL DESIGN: We developed a clinically practical pipeline to clarify the relationship between dosimetric features and outcomes by identifying key variables. We processed data from a cohort of 130 patients treated with proton therapy for brain and head and neck tumors, utilizing an expert-augmented Bayesian network to understand variable interdependencies and assess structural dependencies. Critical evaluation involved a 3-level grading system for each network connection and a Markov blanket analysis to identify variables directly impacting necrosis risk. Statistical assessments included log-likelihood ratio (LLR), integrated discrimination index (IDI), net reclassification index (NRI), and receiver operating characteristic (ROC).

RESULTS: The analysis highlighted tumor location and proximity to critical structures like white matter and ventricles as major determinants of necrosis risk. The majority of network connections were clinically supported, with quantitative measures confirming the significance of these variables in patient stratification (LLR=12.17, p=0.016; IDI=0.15; NRI=0.74). The ROC curve area was 0.66, emphasizing the discriminative value of non-dosimetric variables.

CONCLUSIONS: Key patient variables critical to understanding brain necrosis post-RT were identified, aiding the study of dosimetric impacts and providing treatment confounders and moderators. This pipeline aims to enhance outcome assessments by revealing at-risk patients, offering a versatile tool for broader applications in RT to improve treatment personalization in different disease sites.

PMID:39106090 | DOI:10.1158/1078-0432.CCR-24-1215

JAMA Netw Open. 2024 Aug 1;7(8):e2426830. doi: 10.1001/jamanetworkopen.2024.26830.

NO ABSTRACT

PMID:39106071 | DOI:10.1001/jamanetworkopen.2024.26830

JAMA Netw Open. 2024 Aug 1;7(8):e2425993. doi: 10.1001/jamanetworkopen.2024.25993.

NO ABSTRACT

PMID:39106070 | DOI:10.1001/jamanetworkopen.2024.25993

JAMA Netw Open. 2024 Aug 1;7(8):e2425288. doi: 10.1001/jamanetworkopen.2024.25288.

ABSTRACT

IMPORTANCE: Clinical trial data on adjuvant therapy in patients with non-clear cell renal cell carcinoma (RCC) are scant.

OBJECTIVE: To evaluate the effect of adjuvant everolimus after nephrectomy on recurrence-free survival (RFS) and overall survival (OS) in patients with localized papillary and chromophobe RCC.

DESIGN, SETTING, AND PARTICIPANTS: This prespecified subgroup analysis of a phase 3 randomized clinical trial, EVEREST, included patients enrolled between April 1, 2011, and September 15, 2016. Eligible patients had fully resected RCC at intermediate-high risk (pT1 grade 3-4, N0 to pT3a grade 1-2, N0) or very-high risk (pT3a grade 3-4 to pT4 any grade or N+) for recurrence who had received radical or partial nephrectomy. Final analyses was completed in March 2022.

INTERVENTION: The intervention group received 54 weeks of everolimus (10 mg orally daily); the control group received a matching placebo.

MAIN OUTCOMES AND MEASURES: The main outcomes were RFS, OS, and rates of adverse events. For testing the hazard ratio (HR) for treatment effect, a Cox regression model was used for both OS and RFS.

RESULTS: Of 1545 adult patients with treatment-naive, nonmetastatic, fully resected RCC in EVEREST, 109 had papillary RCC (median [range] age, 60 [19-81] years; 82 [75%] male; 50 patients [46%] with very high-risk disease) and 99 had chromophobe RCC (median [range] age 51 [18-71] years; 53 [54%] male; 34 patients [34%] with very high-risk disease). Among 57 patients with papillary RCC in the intervention group, 26 (46%) completed 54 weeks of treatment, and among 53 patients with chromophobe RCC in the intervention group, 26 (49%) completed 54 weeks of treatment. With a median (IQR) follow-up of 76 (61-96) months, adjuvant everolimus did not improve RFS compared with placebo in either papillary RCC (5-year RFS: 62% vs 70%; HR, 1.19; 95% CI, 0.61-2.33; P = .61) or chromophobe RCC (5-year RFS: 79% vs 77%; HR, 0.89; 95% CI, 0.37-2.13; P = .79). In the combined non-clear RCC cohort, grade 3 or higher adverse events occurred in 48% of patients who received everolimus and 9% of patients who received placebo.

CONCLUSIONS AND RELEVANCE: In this clinical trial assessing the use of adjuvant everolimus, postoperative everolimus did not show evidence of improved RFS among patients with papillary or chromophobe RCC, and results from the study do not support adjuvant everolimus for this cohort. However, since the lower bounds of the 95% CIs were 0.61 and 0.89, respectively, potential treatment benefit in these subgroups cannot be ruled out.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01120249.

PMID:39106067 | DOI:10.1001/jamanetworkopen.2024.25288

JAMA Netw Open. 2024 Aug 1;7(8):e2426076. doi: 10.1001/jamanetworkopen.2024.26076.

ABSTRACT

IMPORTANCE: The role of olanzapine has not been adequately evaluated in moderately emetogenic chemotherapy (MEC) regimens with or without neurokinin-1 receptor antagonists.

OBJECTIVE: To evaluate whether addition of olanzapine to an MEC regimen reduces nausea, vomiting, and use of nausea rescue medications among patients with solid malignant tumors.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label phase 3 randomized clinical trial included patients aged 18 years or older with solid malignant tumors who were receiving oxaliplatin-, carboplatin-, or irinotecan-based chemotherapy. The trial was conducted at 3 institutes in India from March 26, 2019, to August 26, 2023; the final cutoff date for analysis was September 10, 2023.

EXPOSURE: Patients were randomized 1:1 to dexamethasone, aprepitant, and palonosetron with olanzapine (experimental group) or without olanzapine (observation group). The experimental group received 10 mg of olanzapine orally once at night on days 1 through 3 of the chemotherapy regimen.

MAIN OUTCOMES AND MEASURES: The primary end point was complete response (CR), defined as the proportion of patients with no vomiting, no significant nausea (scored as <5 on a visual analog scale of 1 to 100), and no use of rescue medications for nausea. Secondary end points included the proportion of patients experiencing nausea and chemotherapy-induced nausea and vomiting (CINV), receiving rescue medications, and experiencing adverse events.

RESULTS: A total of 560 patients (259 [64%] male; median age, 51 years [range, 19-80 years]) were randomized. The analysis included 544 patients with evaluable data (274 assigned to olanzapine and 270 to observation). Baseline characteristics were evenly matched between the 2 groups. The proportion of patients with CR was significantly greater in the group with (248 [91%]) than without (222 [82%]) olanzapine in the overall 120-hour treatment period (P = .005). Likewise, there were significant differences between the olanzapine and observation groups for nausea control (264 [96%] vs 234 [87%]; P < .001) and CINV (262 [96%] vs 245 [91%]; P = .02) during the overall assessment period, and the proportion of patients receiving rescue medications significantly increased in the observation group (30 [11%]) compared with the olanzapine group (11 [4%]) (P = .001). Grade 1 somnolence was reported by 27 patients (10%) following administration of chemotherapy and olanzapine and by no patients in the observation group.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the addition of olanzapine significantly improved CR rates as well as nausea and vomiting prevention rates in chemotherapy-naive patients who were receiving MEC regimens containing oxaliplatin, carboplatin, or irinotecan. These findings suggest that use of olanzapine should be considered as one of the standards of care in these chemotherapy regimens.

TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI) Identifier: CTRI/2018/12/016643.

PMID:39106066 | DOI:10.1001/jamanetworkopen.2024.26076

JAMA Netw Open. 2024 Aug 1;7(8):e2426209. doi: 10.1001/jamanetworkopen.2024.26209.

ABSTRACT

IMPORTANCE: Deliberate self-poisoning using pesticides as a means of suicide is an important public health problem in low- and middle-income countries. Three highly toxic pesticides-dimethoate, fenthion, and paraquat-were removed from the market in Sri Lanka between 2008 and 2011. In 2015, less toxic pesticides (chlorpyrifos, glyphosate, carbofuran, and carbaryl) were restricted. Subsequent outcomes have not been well described.

OBJECTIVE: To explore the association of pesticide bans with pesticide self-poisonings and in-hospital deaths.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study with an interrupted time series design, data were prospectively collected on all patients with deliberate self-poisonings presenting to 10 Sri Lankan hospitals between March 31, 2002, and December 31, 2019, and analyzed by aggregated types of poisoning. The correlates of pesticide bans were estimated within the pesticide group and on self-poisonings within other substance groups. The data analysis was performed between April 1, 2002, and December 31, 2019.

EXPOSURES: Implementation of 2 sets of pesticide bans.

MAIN OUTCOMES AND MEASURES: The main outcomes were changes in hospital presentations and in-hospital deaths related to pesticide self-poisoning as measured using segmented Poisson regression.

RESULTS: A total of 79 780 patients (median [IQR] age, 24 [18-34] years; 50.1% male) with self-poisoning from all causes were admitted to the study hospitals, with 29 389 poisonings (36.8%) due to pesticides. A total of 2859 patients died, 2084 (72.9%) of whom had ingested a pesticide. The first restrictions that targeted acutely toxic, highly hazardous pesticides were associated with an abrupt and sustained decline of the proportion of poisonings with pesticides (rate ratio [RR], 0.85; 95% CI, 0.78-0.92) over the study period and increases in poisonings with medications (RR, 1.11; 95% CI, 1.02-1.21) and household and industrial chemicals (RR, 1.20; 95% CI, 1.05-1.36). The overall case fatality of pesticides significantly decreased (RR, 0.33; 95% CI, 0.26-0.42) following the implementation of the 2008 to 2011 restrictions of highly hazardous pesticides. Following the 2015 restrictions of low-toxicity pesticides, hospitalizations were unchanged, and the number of deaths increased (RR, 1.98; 95% CI, 1.39-2.83).

CONCLUSIONS AND RELEVANCE: These findings support the restriction of acutely toxic pesticides in resource-poor countries to help reduce hospitalization for and deaths from deliberate self-poisonings and caution against arbitrary bans of less toxic pesticides while more toxic pesticides remain available.

PMID:39106063 | DOI:10.1001/jamanetworkopen.2024.26209