Category: Statistics

JMIR Cardio. 2023 Jun 20;7:e45352. doi: 10.2196/45352.

ABSTRACT

BACKGROUND: The prediction of posttransplant health outcomes for pediatric heart transplantation is critical for risk stratification and high-quality posttransplant care.

OBJECTIVE: The purpose of this study was to examine the use of machine learning (ML) models to predict rejection and mortality for pediatric heart transplant recipients.

METHODS: Various ML models were used to predict rejection and mortality at 1, 3, and 5 years after transplantation in pediatric heart transplant recipients using United Network for Organ Sharing data from 1987 to 2019. The variables used for predicting posttransplant outcomes included donor and recipient as well as medical and social factors. We evaluated 7 ML models-extreme gradient boosting (XGBoost), logistic regression, support vector machine, random forest (RF), stochastic gradient descent, multilayer perceptron, and adaptive boosting (AdaBoost)-as well as a deep learning model with 2 hidden layers with 100 neurons and a rectified linear unit (ReLU) activation function followed by batch normalization for each and a classification head with a softmax activation function. We used 10-fold cross-validation to evaluate model performance. Shapley additive explanations (SHAP) values were calculated to estimate the importance of each variable for prediction.

RESULTS: RF and AdaBoost models were the best-performing algorithms for different prediction windows across outcomes. RF outperformed other ML algorithms in predicting 5 of the 6 outcomes (area under the receiver operating characteristic curve [AUROC] 0.664 and 0.706 for 1-year and 3-year rejection, respectively, and AUROC 0.697, 0.758, and 0.763 for 1-year, 3-year, and 5-year mortality, respectively). AdaBoost achieved the best performance for prediction of 5-year rejection (AUROC 0.705).

CONCLUSIONS: This study demonstrates the comparative utility of ML approaches for modeling posttransplant health outcomes using registry data. ML approaches can identify unique risk factors and their complex relationship with outcomes, thereby identifying patients considered to be at risk and informing the transplant community about the potential of these innovative approaches to improve pediatric care after heart transplantation. Future studies are required to translate the information derived from prediction models to optimize counseling, clinical care, and decision-making within pediatric organ transplant centers.

PMID:37338974 | DOI:10.2196/45352

Stat Methods Med Res. 2023 Jun 20:9622802231181220. doi: 10.1177/09622802231181220. Online ahead of print.

ABSTRACT

In clinical research, it is important to study whether certain clinical factors or exposures have causal effects on clinical and patient-reported outcomes such as toxicities, quality of life, and self-reported symptoms, which can help improve patient care. Usually, such outcomes are recorded as multiple variables with different distributions. Mendelian randomization (MR) is a commonly used technique for causal inference with the help of genetic instrumental variables to deal with observed and unobserved confounders. Nevertheless, the current methodology of MR for multiple outcomes only focuses on one outcome at a time, meaning that it does not consider the correlation structure of multiple outcomes, which may lead to a loss of statistical power. In situations with multiple outcomes of interest, especially when there are mixed correlated outcomes with different distributions, it is much more desirable to jointly analyze them with a multivariate approach. Some multivariate methods have been proposed to model mixed outcomes; however, they do not incorporate instrumental variables and cannot handle unmeasured confounders. To overcome the above challenges, we propose a two-stage multivariate Mendelian randomization method (MRMO) that can perform multivariate analysis of mixed outcomes using genetic instrumental variables. We demonstrate that our proposed MRMO algorithm can gain power over the existing univariate MR method through simulation studies and a clinical application on a randomized Phase III clinical trial study on colorectal cancer patients.

PMID:37338962 | DOI:10.1177/09622802231181220

Stat Methods Med Res. 2023 Jun 20:9622802231181224. doi: 10.1177/09622802231181224. Online ahead of print.

ABSTRACT

Censored data frequently appeared in applications across a variety of different areas like epidemiology or medical research. Traditionally statistical inference on this data mechanism was based on some pre-assigned models that will suffer from the risk of model-misspecification. This article proposes a two-folded shrinkage procedure for simultaneous structure identification and variable selection of the semiparametric accelerated failure additive model with right-censored data, in which the nonparametric functions are addressed by spline approximation. Under some regularity conditions, the consistency of model structure identification is theoretically established in the sense that the proposed method can automatically separate the linear and zero components from the nonlinear ones with probability approaching to one. Detailed issues in computation and turning parameter selection are also discussed. Finally, we illustrate the proposed method by some simulation studies and two real data applications to the primary biliary cirrhosis data and skin cutaneous melanoma data.

PMID:37338958 | DOI:10.1177/09622802231181224

J Bone Miner Res. 2023 Jun 20. doi: 10.1002/jbmr.4871. Online ahead of print.

ABSTRACT

Postoperative hypoparathyroidism (PO-hypoPT) is an uncommon complication of total thyroidectomy in thyroid cancer patients. While long-term hypoPT causes characteristic changes in bone metabolism, the risk of fractures in hypoPT remains inconclusive. We investigated the risk of fractures in Korean thyroid cancer patients with PO-hypoPT. This was a retrospective cohort study using data from the Korea Central Cancer Registry and Korean National Health Insurance Service. We analyzed 115,821 thyroid cancer patients aged ≥18 years, who underwent total thyroidectomy between 2008 and 2016. The risk of any fractures, including vertebral, hip, humerus, and wrist fractures, according to parathyroid function after total thyroidectomy was analyzed using the multivariable Cox proportional hazard model. The PO-hypoPT and preserved parathyroid function groups included 8,789 (7.6%) and 107,032 (92.4%) patients, respectively. Over a mean follow-up duration of 4.8 years, 159 (1.8%) and 2,390 (2.2%) fractures occurred in the PO-hypoPT and preserved parathyroid function groups, respectively. The risk of any fractures was significantly lower in the PO-hypoPT group than in the preserved parathyroid function group (HR, 0.83; 95% CI, 0.70-0.98; P=0.037) after adjusting for confounders. Regarding the fracture site, only the risk of vertebral fractures was significantly lower in the PO-hypoPT group compared to the preserved parathyroid function group (HR, 0.67; 95% CI, 0.47-0.96; P=0.028) after adjusting for confounders. Subgroup analyses showed that bone mineral density measurements and calcium supplementation interacted with the relationship between PO-hypoPT and the risk of any fractures (P for interactions=0.010 and 0.017, respectively). PO-hypoPT was associated with a lower risk of fractures in thyroid cancer patients, especially at the vertebra. The relatively low bone turnover caused by PO-hypoPT and appropriate management for PO-hypoPT with active vitamin D and calcium may prevent the deterioration of skeletal health in thyroid cancer patients who can easily be exposed to long-term overtreatment with levothyroxine. This article is protected by copyright. All rights reserved.

PMID:37338940 | DOI:10.1002/jbmr.4871

Int J Periodontics Restorative Dent. 2023 Jun 20. doi: 10.11607/prd.6013. Online ahead of print.

ABSTRACT

The aim of this retrospective study is to evaluate the performance of implants placed with the All-on-4 technique after a mean time in function of 9 years. Thirty-four patients treated with 156 implants were selected for this study. Eighteen patients underwent teeth extraction on the day of implant placement (group D); 16 were already edentulous (group E). A peri-apical radiograph was taken after a mean of 9 years (range: 5 to 14 years). Success, survival rate, and prevalence of peri-implantitis were calculated. Statistical analysis was used to assess comparisons between groups. After a mean follow-up time of 9 years, the cumulative survival rate was 97.4%, and the success rate was 77.4%. The difference between initial and final radiographs resulted in a mean marginal bone loss (MBL) of 1.3 ± 1.06 mm (range: 0.1 to 5.3 mm). No differences were shown between group D and group E. Fifteen (9.6%) implants in 9 (26.5%) patients were affected by peri-implantitis. This study shows that the All-on-4 technique is a reliable treatment for both edentulous patients and patients that need to undergo dental extractions, with a long follow up. MBL found in this study is similar to MBL around implants used in other rehabilitation types.

PMID:37338922 | DOI:10.11607/prd.6013

Medeni Med J. 2023 Jun 20;38(2):120-127. doi: 10.4274/MMJ.galenos.2023.85688.

ABSTRACT

OBJECTIVE: The preferred therapy for staghorn stones and large kidney stones is percutaneous nephrolithotomy (PCNL). Ultrasound-guided PCNL has definite advantages over fluoroscopy-guided PCNL. Preoperative characteristics are essential to assess better surgical outcomes. The goal of this study was to analyze the correlation of hydronephrosis with surgical outcomes after ultrasound-guided supine PCNL.

METHODS: A retrospective study was conducted at Doris Sylvanus General Hospital. Data of the patients was obtained from hospital records. Hundred and five patients underwent ultrasound-guided PCNL in the supine position from August 2020 to August 2022. Data were analyzed using SPSS 16.0.

RESULTS: The presence of hydronephrosis was 85 (80.95%), which consisted of Grade I 15 (14.30%), Grade II 25 (23.80%), Grade III 28 (26.70%), and Grade IV 17 (16.20%). In our study analysis, complications occurred in 16 patients (15.23%). Grade I complications of the Clavien-Dindo classification was of in 4 cases, 11 cases of grade 2 complications, and 1 patient died. The statistical result was the relationship between grade hydronephrosis and the grade of complication using the modified Clavien-Dindo system. We found a p-value of 0.207 (>0.05), and there is no statistically significant relationship p=0.382 and r=-0.086 was a negative correlation. There is also no statistically significant relationship between hydronephrosis and stone clearance with p=0.310.

CONCLUSIONS: The use of ultrasonographic guidance PCNL has been reported as a safe and effective procedure for the management of large renal stones. In this study, there was no correlation or signification between hydronephrosis and surgical outcome after ultrasound-guided supine PCNL.

PMID:37338913 | DOI:10.4274/MMJ.galenos.2023.85688

JAMA Netw Open. 2023 Jun 1;6(6):e2318919. doi: 10.1001/jamanetworkopen.2023.18919.

ABSTRACT

IMPORTANCE: Understanding the association of civil violence with mental disorders is important for developing effective postconflict recovery policies.

OBJECTIVE: To estimate the association between exposure to civil violence and the subsequent onset and persistence of common mental disorders (in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]) in representative surveys of civilians from countries that have experienced civil violence since World War II.

DESIGN, SETTING, AND PARTICIPANTS: This study used data from cross-sectional World Health Organization World Mental Health (WMH) surveys administered to households between February 5, 2001, and January 5, 2022, in 7 countries that experienced periods of civil violence after World War II (Argentina, Colombia, Lebanon, Nigeria, Northern Ireland, Peru, and South Africa). Data from respondents in other WMH surveys who immigrated from countries with civil violence in Africa and Latin America were also included. Representative samples comprised adults (aged ≥18 years) from eligible countries. Data analysis was performed from February 10 to 13, 2023.

EXPOSURES: Exposure was defined as a self-report of having been a civilian in a war zone or region of terror. Related stressors (being displaced, witnessing atrocities, or being a combatant) were also assessed. Exposures occurred a median of 21 (IQR, 12-30) years before the interview.

MAIN OUTCOMES AND MEASURES: The main outcome was the retrospectively reported lifetime prevalence and 12-month persistence (estimated by calculating 12-month prevalence among lifetime cases) of DSM-IV anxiety, mood, and externalizing (alcohol use, illicit drug use, or intermittent explosive) disorders.

RESULTS: This study included 18 212 respondents from 7 countries. Of these individuals, 2096 reported that they were exposed to civil violence (56.5% were men; median age, 40 [IQR, 30-52] years) and 16 116 were not exposed (45.2% were men; median age, 35 [IQR, 26-48] years). Respondents who reported being exposed to civil violence had a significantly elevated onset risk of anxiety (risk ratio [RR], 1.8 [95% CI, 1.5-2.1]), mood (RR, 1.5 [95% CI, 1.3-1.7]), and externalizing (RR, 1.6 [95% CI, 1.3-1.9]) disorders. Combatants additionally had a significantly elevated onset risk of anxiety disorders (RR, 2.0 [95% CI, 1.3-3.1]) and refugees had an increased onset risk of mood (RR, 1.5 [95% CI, 1.1-2.0]) and externalizing (RR, 1.6 [95% CI, 1.0-2.4]) disorders. Elevated disorder onset risks persisted for more than 2 decades if conflicts persisted but not after either termination of hostilities or emigration. Persistence (ie, 12-month prevalence among respondents with lifetime prevalence of the disorder), in comparison, was generally not associated with exposure.

CONCLUSIONS: In this survey study of exposure to civil violence, exposure was associated with an elevated risk of mental disorders among civilians for many years after initial exposure. These findings suggest that policy makers should recognize these associations when projecting future mental disorder treatment needs in countries experiencing civil violence and among affected migrants.

PMID:37338903 | DOI:10.1001/jamanetworkopen.2023.18919

JAMA Intern Med. 2023 Jun 20. doi: 10.1001/jamainternmed.2023.2215. Online ahead of print.

ABSTRACT

IMPORTANCE: Patients with end-stage kidney disease (ESKD) undergoing long-term hemodialysis often experience a high burden of debilitating symptoms for which effective treatment options are limited.

OBJECTIVE: To compare the effectiveness of a stepped collaborative care intervention vs attention control for reducing fatigue, pain, and depression among patients with ESKD undergoing long-term hemodialysis.

DESIGN, SETTING, AND PARTICIPANTS: Technology Assisted Stepped Collaborative Care (TĀCcare) was a parallel-group, single-blinded, randomized clinical trial of adult (≥18 years) patients undergoing long-term hemodialysis and experiencing clinically significant levels of fatigue, pain, and/or depression for which they were considering treatment. The trial took place in 2 US states (New Mexico and Pennsylvania) from March 1, 2018, to June 31, 2022. Data analyses were performed from July 1, 2022, to April 10, 2023.

INTERVENTIONS: The intervention group received 12 weekly sessions of cognitive behavioral therapy delivered via telehealth in the hemodialysis unit or patient home, and/or pharmacotherapy using a stepped approach in collaboration with dialysis and primary care teams. The attention control group received 6 telehealth sessions of health education.

MAIN OUTCOMES AND MEASURES: The coprimary outcomes were changes in fatigue (measured using the Functional Assessment of Chronic Illness Therapy Fatigue), average pain severity (Brief Pain Inventory), and/or depression (Beck Depression Inventory-II) scores at 3 months. Patients were followed up for 12 months to assess maintenance of intervention effects.

RESULTS: There were 160 participants (mean [SD] age, 58 [14] years; 72 [45%] women and 88 [55%] men; 21 [13%] American Indian, 45 [28%] Black, 28 [18%] Hispanic, and 83 [52%] White individuals) randomized, 83 to the intervention and 77 to the control group. In the intention-to-treat analyses, when compared with controls, patients in the intervention group experienced statistically and clinically significant reductions in fatigue (mean difference [md], 2.81; 95% CI, 0.86 to 4.75; P = .01) and pain severity (md, -0.96; 95% CI, -1.70 to -0.23; P = .02) at 3 months. These effects were sustained at 6 months (md, 3.73; 95% CI, 0.87 to 6.60; P = .03; and BPI, -1.49; 95% CI, -2.58 to -0.40; P = .02). Improvement in depression at 3 months was statistically significant but small (md -1.73; 95% CI, -3.18 to -0.28; P = .02). Adverse events were similar in both groups.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that a technology assisted stepped collaborative care intervention delivered during hemodialysis led to modest but clinically meaningful improvements in fatigue and pain at 3 months vs the control group, with effects sustained until 6 months.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03440853.

PMID:37338898 | DOI:10.1001/jamainternmed.2023.2215

JAMA Neurol. 2023 Jun 20. doi: 10.1001/jamaneurol.2023.1660. Online ahead of print.

ABSTRACT

IMPORTANCE: ApTOLL is a TLR4 antagonist with proven preclinical neuroprotective effect and a safe profile in healthy volunteers.

OBJECTIVE: To assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke.

DESIGN, SETTING, AND PARTICIPANTS: This phase 1b/2a, double-blind, randomized, placebo-controlled study was conducted at 15 sites in Spain and France from 2020 to 2022. Participants included patients aged 18 to 90 years who had ischemic stroke due to large vessel occlusion and were seen within 6 hours after stroke onset; other criteria were an Alberta Stroke Program Early CT Score of 6 to 10, estimated infarct core volume on baseline computed tomography perfusion of 5 to 70 mL, and the intention to undergo EVT. During the study period, 4174 patients underwent EVT.

INTERVENTIONS: In phase 1b, 0.025, 0.05, 0.1, or 0.2 mg/kg of ApTOLL or placebo; in phase 2a, 0.05 or 0.2 mg/kg of ApTOLL or placebo; and in both phases, treatment with EVT and intravenous thrombolysis if indicated.

MAIN OUTCOMES AND MEASURES: The primary end point was the safety of ApTOLL based on death, symptomatic intracranial hemorrhage (sICH), malignant stroke, and recurrent stroke. Secondary efficacy end points included final infarct volume (via MRI at 72 hours), NIHSS score at 72 hours, and disability at 90 days (modified Rankin Scale [mRS] score).

RESULTS: In phase Ib, 32 patients were allocated evenly to the 4 dose groups. After phase 1b was completed with no safety concerns, 2 doses were selected for phase 2a; these 119 patients were randomized to receive ApTOLL, 0.05 mg/kg (n = 36); ApTOLL, 0.2 mg/kg (n = 36), or placebo (n = 47) in a 1:1:√2 ratio. The pooled population of 139 patients had a mean (SD) age of 70 (12) years, 81 patients (58%) were male, and 58 (42%) were female. The primary end point occurred in 16 of 55 patients (29%) receiving placebo (10 deaths [18.2%], 4 sICH [7.3%], 4 malignant strokes [7.3%], and 2 recurrent strokes [3.6%]); in 15 of 42 patients (36%) receiving ApTOLL, 0.05 mg/kg (11 deaths [26.2%], 3 sICH [7.2%], 2 malignant strokes [4.8%], and 2 recurrent strokes [4.8%]); and in 6 of 42 patients (14%) receiving ApTOLL, 0.2 mg/kg (2 deaths [4.8%], 2 sICH [4.8%], and 3 recurrent strokes [7.1%]). ApTOLL, 0.2 mg/kg, was associated with lower NIHSS score at 72 hours (mean difference log-transformed vs placebo, -45%; 95% CI, -67% to -10%), smaller final infarct volume (mean difference log-transformed vs placebo, -42%; 95% CI, -66% to 1%), and lower degrees of disability at 90 days (common odds ratio for a better outcome vs placebo, 2.44; 95% CI, 1.76 to 5.00).

CONCLUSIONS AND RELEVANCE: In acute ischemic stroke, 0.2 mg/kg of ApTOLL administered within 6 hours of onset in combination with EVT was safe and associated with a potential meaningful clinical effect, reducing mortality and disability at 90 days compared with placebo. These preliminary findings await confirmation from larger pivotal trials.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04734548.

PMID:37338893 | DOI:10.1001/jamaneurol.2023.1660