Category: Nevin Manimala

Biostatistics. 2022 Apr 6:kxac007. doi: 10.1093/biostatistics/kxac007. Online ahead of print.

ABSTRACT

Considerable statistical work done on dynamic treatment regimes (DTRs) is in the frequentist paradigm, but Bayesian methods may have much to offer in this setting as they allow for the appropriate representation and propagation of uncertainty, including at the individual level. In this work, we extend the use of recently developed Bayesian methods for Marginal Structural Models to arrive at inference of DTRs. We do this (i) by linking the observational world with a world in which all patients are randomized to a DTR, thereby allowing for causal inference and then (ii) by maximizing a posterior predictive utility, where the posterior distribution has been obtained from nonparametric prior assumptions on the observational world data-generating process. Our approach relies on Bayesian semiparametric inference, where inference about a finite-dimensional parameter is made all while working within an infinite-dimensional space of distributions. We further study Bayesian inference of DTRs in the double robust setting by using posterior predictive inference and the nonparametric Bayesian bootstrap. The proposed methods allow for uncertainty quantification at the individual level, thereby enabling personalized decision-making. We examine the performance of these methods via simulation and demonstrate their utility by exploring whether to adapt HIV therapy to a measure of patients’ liver health, in order to minimize liver scarring.

PMID:35385100 | DOI:10.1093/biostatistics/kxac007

JAMA Surg. 2022 Apr 6:e220135. doi: 10.1001/jamasurg.2022.0135. Online ahead of print.

ABSTRACT

IMPORTANCE: In 2014, Maryland initiated the global budget revenue (GBR) model, placing caps on total hospital expenditures across all care sites. The GBR program aims to reduce unnecessary utilization while maintaining or improving care quality. To date, there has been limited examination of program effects on cancer care.

OBJECTIVE: To compare changes in spending, clinical outcomes, and acute care utilization through 4 years of the GBR program among Medicare beneficiaries who undergo cancer-directed surgery in Maryland vs matched control states.

DESIGN, SETTING, AND PARTICIPANTS: Drawing from a matched pool of hospitals in Maryland (n = 35) and 24 control states with a similar timing of Medicaid expansion (n = 101), we identified Medicare beneficiaries from Maryland and control states who underwent any cancer-directed surgery from 2011 through 2018. Using difference-in-differences analysis, we compared changes in outcomes from before (2011-2013) to after (2015-2018) GBR implementation between patients treated in Maryland and control states. We also performed a subgroup analysis among patients who underwent major surgical procedures that are usually performed in the inpatient setting (cystectomy, esophagectomy, gastrectomy, colorectal resection, nephrectomy, pancreatectomy, and lung resection).

MAIN OUTCOMES AND MEASURES: Thirty-day episode spending, mortality, readmissions, and emergency department (ED) visits.

RESULTS: Relative to Medicare beneficiaries undergoing cancer surgery in control states (n = 4737; 3323 [70.1%] female; 571 [12.1%] dual-eligible; mean [SD] age 74.9 [6.5] years), patients in Maryland (n = 20 320; 14 068 [69.2%] female; 1705 [8.4%] dual-eligible; mean [SD] age 74.9 [6.5] years) had a statistically significant reduction of 2.2 percentage points (95% CI, -4.3 to -0.1) in the 30-day readmission rate. We found no statistically significant changes in 30-day spending, mortality, or ED visits. We report no significant results in the subgroup analysis of patients undergoing major surgical procedures.

CONCLUSIONS AND RELEVANCE: Global budget revenue was not associated with changes in expenditures, ED utilization, or clinical outcomes after cancer-directed surgery through 4 years. There was a modest decline in 30-day readmissions. Specialty-specific definitions of care quality and better alignment across the entire care delivery value chain (ie, physician incentives) may be strategies that could improve delivery of high-value care for beneficiaries undergoing cancer surgery.

PMID:35385085 | DOI:10.1001/jamasurg.2022.0135

JAMA Surg. 2022 Apr 6. doi: 10.1001/jamasurg.2022.0713. Online ahead of print.

ABSTRACT

IMPORTANCE: More than half of patients who undergo knee replacement surgery report substantial acute postoperative pain.

OBJECTIVE: To evaluate the efficacy and cost-effectiveness of periarticular liposomal bupivacaine for recovery and pain management after knee replacement.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, patient-blinded, pragmatic, randomized clinical superiority trial involved 533 participants at 11 institutions within the National Health Service in England. Adults undergoing primary unilateral knee replacement for symptomatic end-stage osteoarthritis were enrolled between March 29, 2018, and February 29, 2020, and followed up for 1 year after surgery. Follow-up was completed March 1, 2021. A per-protocol analysis for each coprimary outcome was performed in addition to the main intention-to-treat analysis.

INTERVENTIONS: Two hundred sixty-six milligrams of liposomal bupivacaine admixed with 100 mg of bupivacaine hydrochloride compared with 100 mg of bupivacaine hydrochloride alone (control) administered by periarticular injection at the time of surgery.

MAIN OUTCOME AND MEASURES: The coprimary outcomes were Quality of Recovery 40 (QoR-40) score at 72 hours and pain visual analog scale (VAS) score area under the curve (AUC) from 6 to 72 hours. Secondary outcomes included QoR-40 and mean pain VAS at days 0 (evening of surgery), 1, 2, and 3; cumulative opioid consumption for 72 hours; functional outcomes and quality of life at 6 weeks, 6 months, and 1 year; and cost-effectiveness for 1 year. Adverse events and serious adverse events up to 12 months after randomization were also assessed.

RESULTS: Among the 533 participants included in the analysis, the mean (SD) age was 69.0 (9.7) years; 287 patients were women (53.8%) and 246 were men (46.2%). Baseline characteristics were balanced between study groups. There was no difference between the liposomal bupivacaine and control groups in QoR-40 score at 72 hours (adjusted mean difference, 0.54 [97.5% CI, -2.05 to 3.13]; P = .64) or the pain VAS score AUC at 6 to 72 hours (-21.5 [97.5% CI, -46.8 to 3.8]; P = .06). Analyses of pain VAS and QoR-40 scores demonstrated only 1 statistically significant difference, with the liposomal bupivacaine arm having lower pain scores the evening of surgery (adjusted difference -0.54 [97.5% CI, -1.07 to -0.02]; P = .02). No difference in cumulative opioid consumption and functional outcomes was detected. Liposomal bupivacaine was not cost-effective compared with the control treatment. No difference in adverse or serious adverse events was found between the liposomal bupivacaine and control groups.

CONCLUSIONS AND RELEVANCE: This study found no difference in postoperative recovery or pain associated with the use of periarticular liposomal bupivacaine compared with bupivacaine hydrochloride alone in patients who underwent knee replacement surgery.

TRIAL REGISTRATION: isrctn.com Identifier: ISRCTN54191675.

PMID:35385072 | DOI:10.1001/jamasurg.2022.0713

Eur J Cardiothorac Surg. 2022 Apr 6:ezac125. doi: 10.1093/ejcts/ezac125. Online ahead of print.

ABSTRACT

OBJECTIVES: We evaluate the mid-term results of mitral valve (MV) repair with patch augmentation of the posterior leaflet in secondary mitral regurgitation.

METHODS: Patients were included after diagnosis of a severe symptomatic secondary MV insufficiency with grade III and IV according to the Carpentier classification IIIb. Indication for a patch augmentation technique was a dilatation of the left ventricle leading to a displacement of the papillary muscles, causing restricted leaflet motion and a marked leaflet tenting height. Data were collected prospectively between December 2011 and March 2020.

RESULTS: In total, 174 patients (mean age: 65 ± 12 years) received an MV repair with patch augmentation of the posterior leaflet and a true-sized remodelling annuloplasty (mean size 30.8 mm). Causes of the MV incompetence were dilatative cardiomyopathy in 126 patients and ischaemic myocardial disease in 48 patients. Concomitant bypass surgery was performed in 28 patients, and the tricuspid valve was repaired in 68 patients. The mean follow-up was 40 ± 28.2 months. There was no 30-day mortality. In-hospital mortality was 1.2% (n = 2); late mortality was 10.9% (n = 19). At 8 years, overall survival was 62.48%, freedom from moderate or severe recurrent mitral regurgitation was 91.9% and freedom from reoperation due to MV insufficiency was 97.1%.

CONCLUSIONS: Augmentation of the posterior MV leaflet in addition to remodelling annuloplasty is a safe and reproducible mitral reconstruction technique that renders sustainable MV competence.

PMID:35385074 | DOI:10.1093/ejcts/ezac125

JAMA Psychiatry. 2022 Apr 6. doi: 10.1001/jamapsychiatry.2022.0465. Online ahead of print.

ABSTRACT

IMPORTANCE: Neurocognitive impairments exist in children at familial high risk (FHR) of schizophrenia and bipolar disorder. Studies on preadolescent developmental courses of neurocognition are important to describe shared and distinct neurodevelopmental pathways in these groups.

OBJECTIVE: To assess the development in specific neurocognitive functions from age 7 to 11 years in children at FHR of schizophrenia or bipolar disorder compared with children in a population-based control (PBC) group.

DESIGN, SETTING, AND PARTICIPANTS: The Danish High Risk and Resilience Study is a prospective, longitudinal, cohort study that collected data from January 1, 2013, to January 31, 2016 (phase 1), and from March 1, 2017, to June 30, 2020 (phase 2). Data were collected at 2 university hospitals in Denmark, and participants included 520 children at FHR of schizophrenia or bipolar disorder along with a PBC group matched with the group of children at FHR of schizophrenia by age, sex, and municipality.

EXPOSURES: Parental schizophrenia, bipolar disorder, or neither.

MAIN OUTCOMES AND MEASURES: Neurocognitive functioning was assessed with validated tests of intelligence, processing speed, attention, memory, verbal fluency, and executive functioning. Multilevel mixed-effects linear regression models with maximum likelihood estimation were used to estimate neurocognitive development from age 7 to 11 years.

RESULTS: At 4-year follow-up, a total of 451 children (mean [SD] age; 11.9 [0.2] years; 208 girls [46.1%]) underwent neurocognitive testing. There were a total of 170 children at FHR of schizophrenia (mean [SD] age, 12.0 [0.3]; 81 girls [47.7%]), 103 children at FHR of bipolar disorder (mean [SD] age, 11.9 [0.2] years; 45 girls [43.7%]), and 178 children in the PBC group (mean [SD] age, 11.9 [0.2] years; 82 girls [46.1%]). At either age 7 or 11 years or at both assessments, 520 children participated in the neurocognitive assessment and were therefore included in the analyses. When correcting for multiple comparisons, no statistically significant time × group interactions were observed across the 3 groups. Compared with the PBC group at 4-year follow-up, children at FHR of schizophrenia showed significant neurocognitive impairment in 7 of 24 neurocognitive measures (29.2%; Cohen d range, 0.29-0.37). Compared with children at FHR of bipolar disorder, children at FHR of schizophrenia had significant neurocognitive impairment in 5 of 24 measures (20.8%; Cohen d range, 0.29-0.38). Children at FHR of bipolar disorder and those in the PBC group did not differ significantly.

CONCLUSIONS AND RELEVANCE: In this cohort study, findings suggest that neurocognitive maturation was comparable across groups of children at FHR of schizophrenia or bipolar disorder compared with PBCs from age 7 to 11 years. Compared with the PBC group, children at FHR of schizophrenia demonstrated widespread, stable, neurocognitive impairments during this period, whereas children at FHR of bipolar disorder showed no neurocognitive impairments, which may indicate distinct neurodevelopmental pathways in children at FHR of schizophrenia and bipolar disorder.

PMID:35385060 | DOI:10.1001/jamapsychiatry.2022.0465

J Vis. 2022 Apr 6;22(5):1. doi: 10.1167/jov.22.5.1.

ABSTRACT

The Open Perimetry Initiative was formed in 2010 with the aim of reducing barriers to clinical research with visual fields and perimetry. Our two principal tools are the Open Perimetry Interface (OPI) and the visualFields package with analytical tools. Both are fully open source. The OPI package contains a growing number of drivers for commercially available perimeters, head-mounted devices, and virtual reality headsets. The visualFields package contains tools for the analysis and visualization of visual field data, including methods to compute deviation values and probability maps. We introduce a new frontend, the opiApp, that provides tools for customization for visual field testing and can be used as a frontend to run the OPI. The app can be used on the Octopus 900 (Haag-Streit), the Compass (iCare), the AP 7000 (Kowa), and the IMO (CREWT) perimeters, with permission from the device manufacturers. The app can also be used on Android phones with virtual reality headsets via a new driver interface, the PhoneHMD, implemented on the OPI. The use of the tools provided by the OPI library is showcased with a custom static automated perimetry test for the full visual field (up to 50 degrees nasally and 80 degrees temporally) developed with the OPI driver for the Octopus 900 and using visualFields for statistical analysis. With more than 60 citations in clinical and translational science journals, this initiative has contributed significantly to expand research in perimetry. The continued support of researchers, clinicians, and industry are key in transforming perimetry research into an open science.

PMID:35385053 | DOI:10.1167/jov.22.5.1

Clin Ter. 2022 Apr 4;173(2):174-179. doi: 10.7417/CT.2022.2412.

ABSTRACT

OBJECTIVE: A versatile and comprehensive approach is required for the treatment of Fibromyalgia syndrome (FMS), which is characterized by multiple physical and psychological symptoms. Highlighting the psychopathology of FMS, might enable us choosing more suitable treatments. From these perspective, we planned to search the cha-racter strength and somepersonality traitsas Forgivingness, Patience, Positivity and Mental Well-Being, which are not searched before in FMS patients.

METHOD: Female patients with widespread musculoskeletal pain meeting the ACR 2010 Fibromyalgia criteria and age- and sex-matched control group were included to the study. All participants were asked to complete a semistructured sociodemographic and clinical data form. The Revised Fibromyalgia Impact Questionnaire (FIQR) was filled. Trait Forgivingness Scale (TFS), 3-Factor Patience scale, Positivity scale and Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) were performed.

RESULTS: A total of 50 female patients with FMS and 36 age- and sex-matched healthy controls were evaluated. The scores of WEMWBSand Positivity Scale were significantly low in FMSgroup (p<001, p<0.001). There were no statistically significant difference in TFSand 3-FPSscores (p=0.751,p=0.364, respectively) (Table 2). There were no statistically significant correlation between parameters in FMS group.

CONCLUSION: The study provides useful insights into the domains of some personality traits of FMS patients. Altough positivity and mental well being were found significantly low, there were no difference in patience and forgivingness.

PMID:35385041 | DOI:10.7417/CT.2022.2412

Clin Ter. 2022 Apr 4;173(2):141-148. doi: 10.7417/CT.2022.2408.

ABSTRACT

BACKGROUND: The aim of the study is to provide scientific evidence on the possibility of using the Corneal point a skin point for measu-rements that can be made on both standard and three-dimensional photographs. Also, we want to demonstrate the stability of corneal point during the growth, to use it as a reference point.

METHODS: A sample of 105 radiographs was reached. A descriptive and longitudinal statistical analysis was performed.

RESULTS: By data analysis we obtained more variability inter-subject of the millimetrically value of the SC plan. For this reason, we consi-dered the relationship between the SN and SC values and not a single value. In the cross-sectional study the T- test analysis did not show a different significant result of variations between SC and SN in both sexes; therefore, we considered these as unique sample.

CONCLUSION: Longitudinal study has a major importance for to esta-blishing the age-related changes. By cross-selection and longitudinal analysis we obtained an overlapping trend of the SN and SC plan. As the SN plan has always been used as a reference plan for cephalometric measurements, although its variations in growth, it can be concluded that the SC plan can be considered equally a reference plan.

PMID:35385037 | DOI:10.7417/CT.2022.2408

Phytochem Anal. 2022 Apr 5. doi: 10.1002/pca.3127. Online ahead of print.

ABSTRACT

INTRODUCTION: The root of Tetrastigma hemsleyanum (RTH) has been widely used as a folk medicine in China. Meanwhile, its stems (STH) and leaves (LTH) are consumed as functional tea and food supplementation. Therefore, it is important to get a better understanding of the distribution of bioactive constituents in different parts of T. hemsleyanum.

OBJECTIVE: To develop a method for quantitative analysis of multiple bioactive constituents and comparing their distribution in RTH, STH and LTH.

METHODS: Ultra-performance liquid chromatography triple quadrupole ion trap tandem mass spectrometry (UPLC-QTRAP-MS/MS) was used for the quantitative analysis. The quantitative data were further analysed by principal component analysis (PCA), hierarchical cluster analysis (HCA) and partial least squares determinant analysis (PLS-DA).

RESULTS: Forty-two constituents in RTH, STH and LTH, including 14 flavonoids, three phenolic acids, 15 amino acids and 10 nucleosides, were quantitatively determined. The contents of flavonoids and phenolic acids in LTH were significantly higher than those in RTH and STH. While the contents of amino acids and nucleosides in LTH were less than those in RTH and STH. Multivariate statistical analysis can significantly classify and distinguish RTH, STH, and LTH.

CONCLUSIONS: The present method would be helpful for the quality control of T. hemsleyanum, and the results would be useful for the efficient utilisation of T. hemsleyanum in the future.

PMID:35383426 | DOI:10.1002/pca.3127

Neurogastroenterol Motil. 2022 Apr 5:e14368. doi: 10.1111/nmo.14368. Online ahead of print.

ABSTRACT

BACKGROUND: Many of the studies on COVID-19 severity and its associated symptoms focus on hospitalized patients. The aim of this study was to investigate the relationship between acute GI symptoms and COVID-19 severity in a clustering-based approach and to determine the risks and epidemiological features of post-COVID-19 Disorders of Gut-Brain Interaction (DGBI) by including both hospitalized and ambulatory patients.

METHODS: The study utilized a two-phase Internet-based survey on: (1) COVID-19 patients’ demographics, comorbidities, symptoms, complications, and hospitalizations and (2) post-COVID-19 DGBI diagnosed according to Rome IV criteria in association with anxiety (GAD-7) and depression (PHQ-9). Statistical analyses included univariate and multivariate tests.

RESULTS: Five distinct clusters of symptomatic subjects were identified based on the presence of GI symptoms, loss of smell, and chest pain, among 1114 participants who tested positive for SARS-CoV-2. GI symptoms were found to be independent risk factors for severe COVID-19; however, they did not always coincide with other severity-related factors such as age >65 years, diabetes mellitus, and Vitamin D deficiency. Of the 164 subjects with a positive test who participated in Phase-2, 108 (66%) fulfilled the criteria for at least one DGBI. The majority (n = 81; 75%) were new-onset DGBI post-COVID-19. Overall, 86% of subjects with one or more post-COVID-19 DGBI had at least one GI symptom during the acute phase of COVID-19, while 14% did not. Depression (65%), but not anxiety (48%), was significantly more common in those with post-COVID-19 DGBI.

CONCLUSION: GI symptoms are associated with a severe COVID-19 among survivors. Long-haulers may develop post-COVID-19 DGBI. Psychiatric disorders are common in post-COVID-19 DGBI.

PMID:35383423 | DOI:10.1111/nmo.14368