Category: Nevin Manimala

JAMA Netw Open. 2022 Jul 1;5(7):e2220957. doi: 10.1001/jamanetworkopen.2022.20957.

ABSTRACT

IMPORTANCE: The effectiveness of monoclonal antibodies (mAbs), casirivimab-imdevimab and sotrovimab, is unknown in patients with mild to moderate COVID-19 caused by the SARS-CoV-2 Delta variant.

OBJECTIVE: To evaluate the effectiveness of mAb against the Delta variant compared with no mAb treatment and to ascertain the comparative effectiveness of casirivimab-imdevimab and sotrovimab.

DESIGN, SETTING, AND PARTICIPANTS: This study comprised 2 parallel studies: (1) a propensity score-matched cohort study of mAb treatment vs no mAb treatment and (2) a randomized comparative effectiveness trial of casirivimab-imdevimab and sotrovimab. The cohort consisted of patients who received mAb treatment at the University of Pittsburgh Medical Center outpatient infusion centers and emergency departments from July 14 to September 29, 2021. Participants were patients with a positive SARS-CoV-2 test result who were eligible to receive mAbs according to emergency use authorization criteria.

EXPOSURE: For the trial, patients were randomized to either intravenous casirivimab-imdevimab or sotrovimab according to a system therapeutic interchange policy.

MAIN OUTCOMES AND MEASURES: For the cohort study, risk ratio (RR) estimates for the primary outcome of hospitalization or death by 28 days were compared between mAb treatment and no mAb treatment using propensity score-matched models. For the comparative effectiveness trial, the primary outcome was hospital-free days (days alive and free of hospitalization) within 28 days after mAb treatment, where patients who died were assigned -1 day in a bayesian cumulative logistic model adjusted for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio (OR) less than 1. Equivalence was defined as a 95% posterior probability that the OR was within a given bound.

RESULTS: A total of 3069 patients (1023 received mAb treatment: mean [SD] age, 53.2 [16.4] years; 569 women [56%]; 2046 had no mAb treatment: mean [SD] age, 52.8 [19.5] years; 1157 women [57%]) were included in the prospective cohort study, and 3558 patients (mean [SD] age, 54 [18] years; 1919 women [54%]) were included in the randomized comparative effectiveness trial. In propensity score-matched models, mAb treatment was associated with reduced risk of hospitalization or death (RR, 0.40; 95% CI, 0.28-0.57) compared with no treatment. Both casirivimab-imdevimab (RR, 0.31; 95% CI, 0.20-0.50) and sotrovimab (RR, 0.60; 95% CI, 0.37-1.00) were associated with reduced hospitalization or death compared with no mAb treatment. In the clinical trial, 2454 patients were randomized to receive casirivimab-imdevimab and 1104 patients were randomized to receive sotrovimab. The median (IQR) hospital-free days were 28 (28-28) for both mAb treatments, the 28-day mortality rate was less than 1% (n = 12) for casirivimab-imdevimab and less than 1% (n = 7) for sotrovimab, and the hospitalization rate by day 28 was 12% (n = 291) for casirivimab-imdevimab and 13% (n = 140) for sotrovimab. Compared with patients who received casirivimab-imdevimab, those who received sotrovimab had a median adjusted OR for hospital-free days of 0.88 (95% credible interval, 0.70-1.11). This OR yielded 86% probability of inferiority for sotrovimab vs casirivimab-imdevimab and 79% probability of equivalence.

CONCLUSIONS AND RELEVANCE: In this propensity score-matched cohort study and randomized comparative effectiveness trial, the effectiveness of casirivimab-imdevimab and sotrovimab against the Delta variant was similar, although the prespecified criteria for statistical inferiority or equivalence were not met. Both mAb treatments were associated with a reduced risk of hospitalization or death in nonhospitalized patients with mild to moderate COVID-19 caused by the Delta variant.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04790786.

PMID:35834252 | DOI:10.1001/jamanetworkopen.2022.20957

JAMA Netw Open. 2022 Jul 1;5(7):e2221699. doi: 10.1001/jamanetworkopen.2022.21699.

ABSTRACT

IMPORTANCE: Ciprofloxacin, 0.3%, plus fluocinolone acetonide, 0.025%, otic solution seems to be efficacious and safe in treating acute otitis externa (AOE) compared with ciprofloxacin, 0.3%, or fluocinolone acetonide, 0.025%, otic solution alone.

OBJECTIVE: To evaluate the superiority of ciprofloxacin, 0.3%, plus fluocinolone acetonide, 0.025%, otic solution compared with ciprofloxacin, 0.3%, or fluocinolone acetonide, 0.025%, otic solution alone in treating AOE.

DESIGN, SETTING, AND PARTICIPANTS: A phase 3 randomized, double-blind, active-controlled clinical trial was conducted between August 1, 2017, and September 14, 2018, at 36 centers in the US. The study population comprised 493 patients aged 6 months or older with AOE of less than 21 days’ duration with otorrhea, moderate or severe otalgia, and edema, as well as a Brighton grading of II or III (tympanic membrane obscure but without systemic illness). Statistical analysis was performed from November 14, 2018, to February 14, 2019.

INTERVENTIONS: Participants were randomly assigned to receive ciprofloxacin plus fluocinolone, ciprofloxacin, or fluocinolone twice daily for 7 days and were evaluated on day 1 (visit 1; baseline), days 3 to 4 (visit 2; conducted via telephone), days 8 to 10 (visit 3; end of treatment), and days 15 to 17 (visit 4; test of cure).

MAIN OUTCOMES AND MEASURES: The primary outcome was therapeutic cure (clinical and microbiological) at the end of the treatment period. The principal secondary end point was the time to end of ear pain. Efficacy analyses were conducted in the microbiological intent-to-treat population, clinical intent-to-treat population, and microbiological intent-to-treat population with Pseudomonas aeruginosa and Staphylococcus aureus.

RESULTS: A total of 493 patients (254 female patients [51.5%]; mean [SD] age, 38.2 [23.1] years) were randomized (197 to receive ciprofloxacin plus fluocinolone, 196 to receive ciprofloxacin, and 100 to receive fluocinolone). Therapeutic cure in the modified intent-to-treat population with ciprofloxacin plus fluocinolone (63 of 103 [61.2%]) was statistically comparable to that of ciprofloxacin (49 of 91 [53.8%]; difference in response rate, 7.3%; 95% CI, -6.6% to 21.2%; P = .30) and fluocinolone (20 of 45 [44.4%]; difference in response rate, 16.7%; 95% CI, -0.6% to 34.0%; P = .06) at visit 3 and significantly superior to ciprofloxacin at visit 4 (90 of 103 [87.4%] vs 69 of 91 [75.8%]; difference in response rate, 11.6%; 95% CI, 0.7%-22.4%; P = .04). A statistically faster resolution of otalgia was achieved among patients treated with ciprofloxacin plus fluocinolone (median, 5.0 days [range, 4.2-6.3 days]) vs ciprofloxacin (median, 5.9 days [range, 4.3-7.3 days]; 95% CI, 4.3-7.3 days; P = .002) or fluocinolone (median, 7.7 days [range, 6.7-9.0 days]; 95% CI, 6.7-9.0 days; P < .001). Ciprofloxacin plus fluocinolone demonstrated statistical superiority in sustained microbiological response vs ciprofloxacin (94 of 103 [91.3%] vs 74 of 91 [81.3%]; difference in response rate, 9.9%; 95% CI, 0.3%-19.6%; P = .04) and fluocinolone (34 of 45 [75.6%]; difference in response rate, 15.7%; 95% CI, 2.0%-29.4%; P = .01) and in the microbiological outcome vs fluocinolone by visit 3 (99 of 103 [96.1%] vs 37 of 45 [82.2%]; difference in response rate, 13.9%; 95% CI, 2.1%-25.7%; P = .01) and ciprofloxacin by visit 4 (97 of 103 [94.2%] vs 77 of 91 [84.6%]; difference in response rate, 9.6%; 95% CI, 0.9%-18.2%; P = .02). Fifteen adverse events related to study medications were registered, all of which were mild or moderate.

CONCLUSIONS AND RELEVANCE: Ciprofloxacin, 0.3%, plus fluocinolone acetonide, 0.025%, otic solution was efficacious and safe in treating AOE but did not demonstrate superiority vs ciprofloxacin, 0.3%, or fluocinolone acetonide, 0.025%, otic solutions alone in the main study end point of therapeutic cure.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03196973.

PMID:35834251 | DOI:10.1001/jamanetworkopen.2022.21699

Psychol Addict Behav. 2022 Jul 14. doi: 10.1037/adb0000854. Online ahead of print.

ABSTRACT

OBJECTIVE: This study explored associations between exposure to other people’s gambling and the prevalence of gambling in the last month, engagement in hard gambling activities (defined as those which occur more frequently, with a quicker determination of outcomes, and/or high payout ratios), and the prevalence of at risk and problem gambling, among a large sample of Australian adolescent school students.

METHOD: In 2017, 6,377 students from Victoria and Queensland answered gambling questions as part of the cross-sectional triennial Australian Secondary Students’ Alcohol and Drug Survey. Students reported on gambling behaviors (gambling in the last month, types of gambling activities), were assessed for problem gambling using the Diagnostic Statistical Manual IV adapted for Juveniles (DSM-IV-[MR]-J), and reported whether people they knew (parents, siblings, other relatives, best friend, or someone else) had gambled in the last month. Logistic regressions explored the relationship between other people’s gambling and student gambling behaviors in the last month.

RESULTS: Approximately, one in five students reported that someone from their household gambled in the last month. Overall, 6% of students reported they had gambled, and 4% gambled on a hard gambling activity, in the previous month; 10% were classified as potentially at risk or problem gamblers. Having a parent, sibling, best friend, another relative, or someone else who gambled in the last month were each significantly associated with the three gambling outcomes.

CONCLUSIONS: There is a need to address the modeling of gambling behaviors by young people’s friends, family, and others, in order to reduce gambling behaviors and problem gambling among Australian adolescents. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:35834199 | DOI:10.1037/adb0000854

JAMA Oncol. 2022 Jul 14. doi: 10.1001/jamaoncol.2022.2319. Online ahead of print.

ABSTRACT

IMPORTANCE: National guidelines endorse treatment with neoadjuvant therapy for borderline resectable pancreatic ductal adenocarcinoma (PDAC), but the optimal strategy remains unclear.

OBJECTIVE: To compare treatment with neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) with or without hypofractionated radiation therapy with historical data and establish standards for therapy in borderline resectable PDAC.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter, randomized phase 2 clinical trial conducted from February 2017 to January 2019 among member institutions of National Clinical Trials Network cooperative groups used standardized quality control measures and included 126 patients, of whom 70 (55.6%) were registered to arm 1 (systemic therapy; 54 randomized, 16 following closure of arm 2 at interim analysis) and 56 (44.4%) to arm 2 (systemic therapy and sequential hypofractionated radiotherapy; all randomized before closure). Data were analyzed by the Alliance Statistics and Data Management Center during September 2021.

INTERVENTIONS: Arm 1: 8 treatment cycles of mFOLFIRINOX (oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2; leucovorin, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2) over 46 hours, administered every 2 weeks. Arm 2: 7 treatment cycles of mFOLFIRINOX followed by stereotactic body radiotherapy (33-40 Gy in 5 fractions) or hypofractionated image-guided radiotherapy (25 Gy in 5 fractions). Patients without disease progression underwent pancreatectomy, which was followed by 4 cycles of treatment with postoperative FOLFOX6 (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; bolus fluorouracil, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2 over 46 hours).

MAIN OUTCOMES AND MEASURES: Each treatment arm’s 18-month overall survival (OS) rate was compared with a historical control rate of 50%. A planned interim analysis mandated closure of either arm for which 11 or fewer of the first 30 accrued patients underwent margin-negative (R0) resection.

RESULTS: Of 126 patients, 62 (49%) were women, and the median (range) age was 64 (37-83) years. Among the first 30 evaluable patients enrolled to each arm, 17 patients in arm 1 (57%) and 10 patients in arm 2 (33%) had undergone R0 resection, leading to closure of arm 2 but continuation to full enrollment in arm 1. The 18-month OS rate of evaluable patients was 66.7% (95% CI, 56.1%-79.4%) in arm 1 and 47.3% (95% CI 35.8%-62.5%) in arm 2. The median OS of evaluable patients in arm 1 and arm 2 was 29.8 (95% CI, 21.1-36.6) months and 17.1 (95% CI, 12.8-24.4) months, respectively.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that treatment with neoadjuvant mFOLFIRINOX alone was associated with favorable OS in patients with borderline resectable PDAC compared with mFOLFIRINOX treatment plus hypofractionated radiotherapy; thus, mFOLFIRINOX represents a reference regimen in this setting.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02839343.

PMID:35834226 | DOI:10.1001/jamaoncol.2022.2319

Rheumatol Ther. 2022 Jul 14. doi: 10.1007/s40744-022-00473-6. Online ahead of print.

ABSTRACT

INTRODUCTION: In patients with rheumatoid arthritis (RA), attaining remission or low disease activity (LDA), as recommended by the treat-to-target approach, has shown to yield improvement in symptoms and quality of life. However, limited evidence from real-world settings is available to support the premise that better disease control is associated with lower healthcare costs. This study fills in evidence gaps regarding the cost of care by RA disease activity (DA) states and by therapy.

METHODS: This retrospective cohort study linked medical and prescription claims from Optum Clinformatics Data Mart to electronic health record data from Illumination Health over 1/1/2010-3/31/2020. Mean annual costs for payers and patients were examined, stratifying on DA state and baseline use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologics, and targeted synthetic (ts)DMARDs. Subgroup analysis examining within-person change in costs pre- and post-initiation of new therapy was also performed. Descriptive statistics, means, and boot-strapped confidence intervals were analyzed by DA state and by RA therapy. Furthermore, multivariate negative binomial regression analysis adjusting for key baseline characteristics was conducted.

RESULTS: Of 2339 eligible patients, 19% were in remission, 40% in LDA, 29% in moderate DA (MDA), and 12% in high DA (HDA) at baseline. Mean annual costs during follow-up were substantially less for patients in remission ($40,072) versus those in MDA ($56,536) and HDA ($59,217). For patients in remission, csDMARD use was associated with the lowest mean annual cost ($25,575), tsDMARD was highest ($75,512), and tumor necrosis factor inhibitor (TNFi) ($69,846) and non-TNFi ($57,507) were intermediate. Among new TNFi (n = 137) and non-TNFi initiators (n = 107), 31% and 26% attained LDA/remission, respectively, and the time to achieve remission/LDA was numerically shorter in TNFi vs. non-TNFi initiators. For those on biologics, mean annual within-person medical and inpatient costs were lower after achieving LDA/remission, although pharmacy costs were higher.

CONCLUSIONS: Cost of care increased with increasing DA state, with patients in remission having the lowest costs. Optimizing DA has the potential for substantial savings in healthcare costs, although may be partially offset by the high cost of targeted RA therapies.

PMID:35834162 | DOI:10.1007/s40744-022-00473-6

Inflammopharmacology. 2022 Jul 14. doi: 10.1007/s10787-022-01029-4. Online ahead of print.

ABSTRACT

BACKGROUND: It is known that severe acute respiratory coronavirus 2 (SARS-CoV-2) is the viral strain responsible for the recent coronavirus disease 2019 (COVID-19) pandemic. Current documents have demonstrated that the virus causes a PGE2 storm in a substantial proportion of patients via upregulating cyclooxygenase-2 (COX-2) and downregulating prostaglandin E2 (PGE2)-degrading enzymes within the host cell.

AIM: Herein, we aimed to study how short-term treatment with celecoxib (Celebrex), a selective COX-2 inhibitor, affects demographic features, early symptoms, O₂ saturation, and hematological indices of cases with COVID-19.

METHODS: A total of 67 confirmed COVID-19 cases with a mild or moderate disease, who had been referred to an institutional hospital in south-eastern Iran from October 2020 to September 2021, were enrolled. Demographic characteristics, symptoms, and hematological indices of the patients were recorded within different time periods. One-way ANOVA or Kruskal-Wallis tests were used to determine differences between data sets based on normal data distribution.

RESULTS: O₂ saturation was statistically different between the control group and patients receiving celecoxib (p = 0.039). There was no marked difference between the groups in terms of the symptoms they experienced (p > 0.05). On the first days following Celebrex therapy, analysis of complete blood counts showed that white blood cell (WBC) counts were markedly lower in patients treated with a high dose of celecoxib (0.4 g/day) than in controls (p = 0.026). However, mean lymphocyte levels in patients receiving a high dose of celecoxib (0.4 g/day) were markedly higher than in patients receiving celecoxib with half of the dose (0.2 g/day) for one week or the untreated subjects (p = 0.004). Changes in platelet count also followed the WBC alteration pattern.

CONCLUSION: Celecoxib is a relatively safe, inexpensive, and widely available drug with non-steroidal anti-inflammatory properties. The therapeutic efficacy of celecoxib depends on the administrated dose. Celecoxib might improve disease-free survival in patients with COVID-19.

PMID:35834150 | DOI:10.1007/s10787-022-01029-4

J Neurooncol. 2022 Jul 14. doi: 10.1007/s11060-022-04082-9. Online ahead of print.

ABSTRACT

PURPOSE: Although rare, brain metastases (BM) from cervical cancer (CC) are highly lethal. Adequate patient selection for specific treatments can improve survival rates in patients afflicted by this condition. This study aimed to describe the characteristics of CC patients who developed BM and overall survival-associated factors. Brain metastasis impact on the overall survival was assessed as a secondary objective.

METHODS: This assessment comprises a retrospective cohort study on 3394 women presenting CC diagnosed between January 2010 and December 2017 at a single referral center. Incident BM cases were included. Descriptive statistics were calculated. Kaplan-Meier curves were used for the survival analysis and a Cox proportional hazards regression model was applied to explore the risk of death according to the analyzed independent variables.

RESULTS: A total of 48 incident BM cases were identified. The median time between CC diagnosis and BM development was 1.5 years. Headaches (29.2%), dizziness/altered balance (29.2%), vertigo (29.2%) and motor disturbances (25.0%) were the most common signs and symptoms at presentation. Median overall survival after BM diagnosis was of 1.6 months (95% CI 0.9-2.3) while in the group of women without BM it was 5.5 years (95% CI 4.9-6.1). Concerning the Cox multivariate analysis, presenting one extracerebral metastases site (HR 2.8; 95% CI 1.3-6.2; p = 0.009) and receiving supportive treatment (HR 13.7; 95% CI 3.1-60.5; p 0.001) were independently associated with the risk of death.

CONCLUSION: The median survival of women with BM following CC was poor. Women without extracerebral metastases and undergoing multimodal treatment displayed better overall survival rates.

PMID:35834147 | DOI:10.1007/s11060-022-04082-9

J Gambl Stud. 2022 Jul 14. doi: 10.1007/s10899-022-10144-4. Online ahead of print.

ABSTRACT

In recent years, account-based player tracking data have been utilized as a potential tool to identify problem gambling online and associated markers of harm. One established marker of harm among problem gamblers is chasing losses, and chasing losses is a key criterion for gambling disorder in the most recent edition of the Diagnostic and Statistical Manual of Mental Disorders. Given the paucity of research with respect to chasing losses among online casino players using account-based data, the present study developed five metrics that may be indicative of chasing behavior: These were (i) within-session chasing, (ii) across-session chasing, (iii) across-days chasing, (iv) regular gambling account depletion, and (v) frequent session depositing. The authors were given access by a European online casino to raw data of all players who had placed at least one bet or wagered at least once during December 2021 (N = 16,771 players from the UK, Spain, and Sweden). Results indicated that frequent session depositing reflected chasing losses better than any of the other four metric operationalizations used. While frequent session depositing appears to be more indicative of chasing losses than the other four metrics, all the metrics provide useful information which can be used to help identify problematic gambling behavior online.

PMID:35834118 | DOI:10.1007/s10899-022-10144-4

Neuroinformatics. 2022 Jul 14. doi: 10.1007/s12021-022-09592-5. Online ahead of print.

ABSTRACT

Resting-state functional magnetic resonance imaging (rs-fMRI) most recently has proved to open a measureless window on functional neurodevelopment in utero. Fetal brain activation and connectivity maps can be heavily influenced by 1) fetal-specific motion effects on the time-series and 2) the accuracy of time-series spatial normalization to a standardized gestational-week (GW) specific fetal template space.Due to the absence of a standardized and generalizable image processing protocol, the objective of the present work was to implement a validated fetal rs-fMRI preprocessing pipeline (RS-FetMRI) divided into 6 inter-dependent preprocessing modules (i.e., M1 to M6) and designed to work entirely as an extension for Statistical Parametric Mapping (SPM).RS-FetMRI pipeline output analyses on rs-fMRI time-series sampled from a cohort of fetuses acquired on both 1.5 T and 3 T MRI scanning systems showed increased efficacy of estimation of the degree of movement coupled with an efficient motion censoring procedure, resulting in increased number of motion-uncorrupted volumes and temporal continuity in fetal rs-fMRI time-series data. Moreover, a “structural-free” SPM-based spatial normalization procedure granted a high degree of spatial overlap with high reproducibility and a significant improvement in whole-brain and parcellation-specific Temporal Signal-to-Noise Ratio (TSNR) mirrored by functional connectivity analysis.To our knowledge, the RS-FetMRI pipeline is the first semi-automatic and easy-to-use standardized fetal rs-fMRI preprocessing pipeline completely integrated in MATLAB-SPM able to remove entry barriers for new research groups into the field of fetal rs-fMRI, for both research or clinical purposes, and ultimately to make future fetal brain connectivity investigations more suitable for comparison and cross-validation.

PMID:35834105 | DOI:10.1007/s12021-022-09592-5

Odontology. 2022 Jul 14. doi: 10.1007/s10266-022-00729-1. Online ahead of print.

ABSTRACT

This study, in which a hundred human teeth with single straight canal were used, focused on the evaluation of contrast solution penetration ability into the simulated lateral canals activated by XP-endo Finisher (XPF), EDDY, Nd:YAG, and Er:YAG laser systems with three different observation methods. The root canals were prepared up to X4 at working length using the ProTaper Next system. The teeth were decalcified and simulated lateral canals were created with #8 K-file at 2, 4, and 6 mm levels. Then the teeth were cleared using methyl salicylate and divided into 5 equal groups according to irrigation activation techniques (CSI, XPF, EDDY, Nd:YAG, and Er:YAG laser). After the contrast solution was activated, images of the simulated lateral canals were obtained by a dental microscope, digital radiography, and CBCT. The contrast solution penetration scores at the 2, 4, and 6 mm levels according to irrigation activation techniques and observation methods were analyzed statistically using Kruskal-Wallis non-parametric analysis of variance Bonferroni test post hoc comparisons. With the other 2 parameters are ignored, the highest and lowest contrast solution penetration were observed at 6 and 2 mm simulated lateral canal levels (p < 0.05), in Er:YAG irrigation activation and CSI technique (p < 0.05), and in direct visual and digital radiographic observation method (p < 0.05), respectively. Within the limits of this study, it was determined that the contrast solution penetration into the simulated lateral canals decreased from the coronal to the apical and achieved with the most effective Er:YAG laser activation technique. In addition, direct visual observation was found to be the best method for the assessment of contrast solution penetration.

PMID:35834067 | DOI:10.1007/s10266-022-00729-1