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Nevin Manimala Statistics

Logistic Regression Analysis of LC-MS/MS Data of Monomers Eluted from Aged Dental Composites: A Supervised Machine-Learning Approach

Anal Chem. 2023 Mar 14. doi: 10.1021/acs.analchem.2c04362. Online ahead of print.

ABSTRACT

Compound identification by database searching that matches experimental with library mass spectra is commonly used in mass spectrometric (MS) data analysis. Vendor software often outputs scores that represent the quality of each spectral match for the identified compounds. However, software-generated identification results can differ drastically depending on the initial search parameters. Machine learning is applied here to provide a statistical evaluation of software-generated compound identification results from experimental tandem MS data. This task was accomplished using the logistic regression algorithm to assign an identification probability value to each identified compound. Logistic regression is usually used for classification, but here it is used to generate identification probabilities without setting a threshold for classification. Liquid chromatography coupled with quadrupole-time-of-flight tandem MS was used to analyze the organic monomers leached from resin-based dental composites in a simulated oral environment. The collected tandem MS data were processed with vendor software, followed by statistical evaluation of these results using logistic regression. The assigned identification probability to each compound provides more confidence in identification beyond solely by database matching. A total of 21 distinct monomers were identified among all samples, including five intact monomers and chemical degradation products of bisphenol A glycidyl methacrylate (BisGMA), oligomers of bisphenol-A ethoxylate methacrylate (BisEMA), triethylene glycol dimethacrylate (TEGDMA), and urethane dimethacrylate (UDMA). The logistic regression model can be used to evaluate any database-matched liquid chromatography-tandem MS result by training a new model using analytical standards of compounds present in a chosen database and then generating identification probabilities for candidates from unknown data using the new model.

PMID:36917068 | DOI:10.1021/acs.analchem.2c04362

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Nevin Manimala Statistics

Association Between California’s State Insurance Gender Nondiscrimination Act and Utilization of Gender-Affirming Surgery

JAMA. 2023 Mar 14;329(10):819-826. doi: 10.1001/jama.2023.0878.

ABSTRACT

IMPORTANCE: Gender-affirming surgery is often beneficial for gender-diverse or -dysphoric patients. Access to gender-affirming surgery is often limited through restrictive legislation and insurance policies.

OBJECTIVE: To investigate the association between California’s 2013 implementation of the Insurance Gender Nondiscrimination Act, which prohibits insurers and health plans from limiting benefits based on a patient’s sex, gender, gender identity, or gender expression, and utilization of gender-affirming surgery among California residents.

DESIGN, SETTING, AND PARTICIPANTS: Population epidemiology study of transgender and gender-diverse patients undergoing gender-affirming surgery (facial, chest, and genital surgery) between 2005 and 2019. Utilization of gender-affirming surgery in California before and after implementation of the Insurance Gender Nondiscrimination Act in July 2013 was compared with utilization in Washington and Arizona, control states chosen because of geographic similarity and because they expanded Medicaid on the same date as California-January 1, 2014. The date of last follow-up was December 31, 2019.

EXPOSURES: California’s Insurance Gender Nondiscrimination Act, implemented on July 9, 2013.

MAIN OUTCOMES AND MEASURES: Receipt of gender-affirming surgery, defined as undergoing at least 1 facial, chest, or genital procedure.

RESULTS: A total of 25 252 patients (California: n = 17 934 [71%]; control: n = 7328 [29%]) had a diagnosis of gender dysphoria. Median ages were 34.0 years in California (with or without gender-affirming surgery), 39 years (IQR, 28-49 years) among those undergoing gender-affirming surgery in control states, and 36 years (IQR, 22-56 years) among those not undergoing gender-affirming surgery in control states. Patients underwent at least 1 gender-affirming surgery within the study period in 2918 (11.6%) admissions-2715 (15.1%) in California vs 203 (2.8%) in control states. There was a statistically significant increase in gender-affirming surgery in the third quarter of July 2013 in California vs control states, coinciding with the timing of the Insurance Gender Nondiscrimination Act (P < .001). Implementation of the policy was associated with an absolute 12.1% (95% CI, 10.3%-13.9%; P < .001) increase in the probability of undergoing gender-affirming surgery in California vs control states observed in the subset of insured patients (13.4% [95% CI, 11.5%-15.4%]; P < .001) but not self-pay patients (-22.6% [95% CI, -32.8% to -12.5%]; P < .001).

CONCLUSIONS AND RELEVANCE: Implementation in California of its Insurance Gender Nondiscrimination Act was associated with a significant increase in utilization of gender-affirming surgery in California compared with the control states Washington and Arizona. These data might inform state legislative efforts to craft policies preventing discrimination in health coverage for state residents, including transgender and gender-diverse patients.

PMID:36917051 | DOI:10.1001/jama.2023.0878

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Nevin Manimala Statistics

Effects of Orthopedic Manual Therapy on Pain Sensitization in Patients with Chronic Musculoskeletal Pain: An Umbrella Review with Meta-Meta-Analysis

Am J Phys Med Rehabil. 2023 Mar 14. doi: 10.1097/PHM.0000000000002239. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this umbrella review with meta-meta-analysis was to assess the effectiveness of orthopedic manual therapy in isolation on pain sensitization in patients with chronic musculoskeletal pain.

DESIGN: A systematic search was performed in different databases including systematic reviews with or without meta-analysis. The outcome measures included were pressure pain threshold, temporal summation, and conditioned pain modulation. We statistically synthesized the results of the different reviews through a random-effect meta-analysis of all standardized mean differences and the corresponding 95% confidence interval reported by each study.

RESULTS: For mechanical hyperalgesia, the meta-meta-analysis of three meta-analysis revealed a statistically significant small-moderate effect of orthopedic manual therapy, with no evidence of heterogeneity and moderate quality evidence. In terms of temporal summation, one meta-analysis revealed a statistically significant small effect of orthopedic manual therapy intervention, with moderate heterogeneity and low quality of evidence. Finally, one review without meta-analysis found that orthopedic manual therapy improved endogenous analgesia with low quality evidence.

CONCLUSION: Orthopedic manual therapy in isolation improved mechanical hyperalgesia with moderate quality evidence, as well as temporal summation and conditioned pain modulation with low quality evidence. However, its effects are limited only to immediate and short-term.

PMID:36917046 | DOI:10.1097/PHM.0000000000002239

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Effects of the Mandibular Functional Units and Soft Tissue on Facial Asymmetry

J Craniofac Surg. 2023 Mar 14. doi: 10.1097/SCS.0000000000009276. Online ahead of print.

ABSTRACT

Mandibular asymmetry has a variety of patterns because they are affected the position and the shape of mandible in addition to the overlying soft tissue. This study aimed to assess the factor in mandibular asymmetry, focusing on each mandibular functional units and the soft tissue thickness in the mandibular angle area. Forty patients who were diagnosed with facial asymmetry and undergone the orthognathic surgery without genioplasty were enrolled in this study. The skeletal patterns of the patients were analyzed by using cone-beam computed tomography data and 3D virtual images divided into 2 categories; the mandibular functional unit length and the soft tissue depth. All difference in bilateral mandibular functional unit lengths had a statistically significant with chin top deviation (P<0.05). The greatest correlation was the condylar unit length compared with other functional units. The soft tissue thickness in the mandibular angle area was not statistically related to chin top deviation (P>0.05), and the soft tissue did not change remarkably after orthognathic surgery (P>0.05). This study suggests that the considerations of a surgical plan for treatment based on the mandibular asymmetry.

PMID:36917036 | DOI:10.1097/SCS.0000000000009276

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Ejaculatory Function following Transperineal Laser Ablation versus TURP for Benign Prostatic Obstruction: A Randomized Trial

BJU Int. 2023 Mar 14. doi: 10.1111/bju.16008. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the reliability of trans-perineal laser ablation of prostate (TPLA) in preserving antegrade ejaculation compared to trans-urethral resection of prostate (TURP).

PATIENTS AND METHODS: In this single-center, prospective, randomized, open-label study, consecutive patients with indication to surgical treatment for benign prostatic obstruction (BPO) were enrolled between January 2020 and September 2021 (NCT04781049). Randomization defined two treatment arms: Group A: patients assigned to TPLA (experimental); Group B: patients assigned to TURP (standard). Primary endpoint was change in ejaculatory function (assessed by EJ-MSHQ) at 1 month after surgery. Secondary endpoints included comparison of visual analogue scale (VAS), changes in sexual function (by IIEF-5), ΔIPSS and ΔQoL, and Qmax improvement at 1-6 months, as appropriate.

RESULTS: Fifty-one patients (26 TPLA versus 25 TURP) were analyzed. No differences were found in the perception of pain assessed by VAS. No differences in IIEF-5 score were found between groups. Distribution of ejaculatory function assessed by the EJ-MSHQ remained unmodified after TPLA (p=0.2) while a median 30% decrease in EJ-MSHQ score was observed after TURP (p=0.01). Absence of antegrade ejaculation was reported in one patient within the TPLA group (18 patients s/p TURP). A statistically significant difference between the treatment groups was found in terms of postoperative Qmax (15.2 (IQR 13.5-18.3) versus 26.0 (IQR 22.0-48.0) ml/s, TPLA versus TURP, p<0.001). Both treatments significantly improved Qmax : mean 23.9 ml/s improvement s/p TURP (95% C.I. 17.1-30.7) versus 6.0 ml/s s/p TPLA (95% C.I. (5.0-7.0); and IPSS: mean 11.6 decrease (95% C.I. 9.7-13.5) versus 5.8 s/p TPLA (95% C.I. (2-9.6) with respect to baseline.

CONCLUSION: In our study, TPLA preserved ejaculatory function in 96% of cases in addition to providing significant relief from BPO.

PMID:36917033 | DOI:10.1111/bju.16008

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Evaluation of clinical performance and safety for the rechargeable InterStim Micro device in overactive bladder subjects: 6-month results from the global postmarket ELITE study

Neurourol Urodyn. 2023 Mar 14. doi: 10.1002/nau.25171. Online ahead of print.

ABSTRACT

AIMS: Sacral neuromodulation (SNM) is an advanced therapy option for the treatment of overactive bladder (OAB), nonobstructive urinary retention, and fecal incontinence. The aim of this ongoing prospective, multicenter, global, postmarket study is to confirm safety and clinical performance of the InterStimTM Micro system for SNM in all indications. Reported here are the results for the OAB cohort through 6-month follow-up.

METHODS: Eligible OAB subjects that had a successful therapy evaluation were enrolled after implant of an InterStim Micro implantable pulse generator (IPG). Subjects completed voiding diaries and the Overactive Bladder Quality of Life questionnaire (OAB-q) at baseline and follow-up visits occurring at 3 months and 6 months postimplant. Safety was evaluated as device-, procedure-, or therapy-related adverse events. The primary objective for the OAB cohort was to demonstrate an improvement in OAB-q Health Related Quality of Life (HRQL) total score at 3 months postimplant compared to baseline.

RESULTS: Sixty-eight OAB subjects were enrolled and implanted with an InterStim Micro IPG. Of those, 67 and 66 subjects completed the 3- and 6-month follow-up visits, respectively. The OAB-q HRQL demonstrated a statistically significant improvement from baseline to 3-month follow-up with an average increase of 33 ± 24 points (n = 67, p < 0.001). The change was also observed at 6-months with an average increase of 31 ± 23 points (n = 65) compared to baseline. Eighty-two percent of subjects achieved the minimally important difference in HRQL score at 3- and 6-month, respectively, with a change of 10 points or greater. The majority of subjects reported that their bladder condition was better at 3-month (92.5%, 62/67) and 6-month (89%, 59/66) compared to before they were treated with SNM therapy delivered by the InterStim Micro system. For subjects with urgency urinary incontinence (UUI), the average change from baseline to follow-up in UUI episodes/day was -3.6 (95% CI: -4.7, -2.6; n = 62) at 3-month and -3.7 (95% CI: -4.7, -2.7; n = 61) at 6-month. Among subjects with urgency-frequency (UF), the average change from baseline to follow up in voids/day was -4.5 (95% CI: -6.3, -2.7; n = 52) at 3-months and -4.4 (95% CI: -6.0, -2.7; n = 52) at 6-month. The cumulative incidence of device-, procedure-, or therapy- related adverse events was 7.4% (5/68). Out of these five related adverse events, there was one serious adverse event (1.5%, implant site pain) at the time of database snapshot.

CONCLUSIONS: These data confirm the safety and clinical performance of the InterStim Micro device for subjects with OAB by demonstrating a significant improvement in OAB-q HRQL score at 3-month. Similar improvements were observed at 6 months in addition to an incidence of adverse events that is comparable to previously reported rates for SNM.

PMID:36917003 | DOI:10.1002/nau.25171

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Efficacy and safety of low-dose spironolactone for chronic kidney disease in type 2 diabetes

J Clin Endocrinol Metab. 2023 Mar 14:dgad144. doi: 10.1210/clinem/dgad144. Online ahead of print.

ABSTRACT

CONTEXT: Although adding spironolactone to renin-angiotensin system blockers reduces albuminuria in adults with chronic kidney disease and type 2 diabetes, it increases the risk of hyperkalemia.

OBJECTIVE: To assess whether a lower dose of spironolactone (12.5 mg/day) reduces the risk of hyperkalemia while maintaining its effect on reducing albuminemia.

DESIGN: Multicenter, open-label, randomized controlled trial.

SETTING: This study was conducted from July 2016 to November 2020 in ambulatory care at three diabetes medical institutions in Japan.

PATIENTS: We enrolled 130 Japanese adults with type 2 diabetes and albuminuria (≥30 mg/gCre), estimated glomerular filtration rate ≥30 mL/min/1.73 m2, and serum potassium level <5.0 mEq/L.

INTERVENTIONS: The participants were randomly assigned to the spironolactone-administered and control groups.

MAIN OUTCOME MEASURES: Changes in urine albumin-to-creatinine ratio (UACR) from baseline over the 24-week interventional period.

RESULTS: The spironolactone group showed a significant reduction in UACR from baseline (mean decrease: 103.47 ± 340.80 mg/gCre) compared with the control group which showed an increased UACR (mean increase: 63.93 ± 310.14 mg/gCre; p = 0.0007, Wilcoxon rank-sum test and t-test). Although the spironolactone group had a statistically significant increase in serum potassium levels, none of the participants had a potassium level ≥5.5 mEq/L at 24 weeks. Further, participants with a higher initial serum potassium level tended to have a smaller increase (estimate -0.37, analysis of covariance).

CONCLUSIONS: Low-dose spironolactone administration reduced albuminuria without causing hyperkalemia. Spironolactone administration, the oldest known and most cost-effective mineralocorticoid receptor antagonist, at lower doses should be reconsidered.

PMID:36916985 | DOI:10.1210/clinem/dgad144

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Safety and Efficacy of Topical Calcineurin Inhibitors in the Treatment of Facial and Genital Psoriasis: A Systematic Review

Acta Derm Venereol. 2023 Mar 14;103:adv00890. doi: 10.2340/actadv.v103.6525.

ABSTRACT

Facial and genital psoriasis impairs quality of life and is challenging to treat because of increased percutaneous penetration and, consequently, increased risk of adverse effects. Topical calcineurin inhibitors are recognized as a valid off-label treatment for these sensitive skin areas, but data on safety and efficacy are limited. This systematic review of the literature included 24 of 3,322 studies (5 randomized controlled trials, 9 open-label studies, 2 case series and 8 case reports). All studies demonstrated positive efficacy; 11 studies found statistically significant reductions in psoriasis severity. Local stinging, burning and itching were the most common short-term adverse effects and were reported in 18 studies. Topical calcineurin inhibitors appear to have an important role in the treatment of facial and genital psoriasis. The drugs are effective and generally well-tolerated with few adverse effects.

PMID:36916954 | DOI:10.2340/actadv.v103.6525

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Emergence of time persistence in a data-driven neural network model

Elife. 2023 Mar 14;12:e79541. doi: 10.7554/eLife.79541. Online ahead of print.

ABSTRACT

Establishing accurate as well as interpretable models of network activity is an open challenge in systems neuroscience. Here we infer an energy-based model of the ARTR, a circuit that controls zebrafish swimming statistics, using functional recordings of the spontaneous activity of hundreds of neurons. Although our model is trained to reproduce the low-order statistics of the network activity at short time-scales, its simulated dynamics quantitatively captures the slowly alternating activity of the ARTR. It further reproduces the modulation of this persistent dynamics by the water temperature and visual stimulation. Mathematical analysis of the model unveils a low-dimensional landscape-based representation of the ARTR activity, where the slow network dynamics reflects Arrhenius-like barriers crossings between metastable states. Our work thus shows how data-driven models built from large neural populations recordings can be reduced to low-dimensional functional models in order to reveal the fundamental mechanisms controlling the collective neuronal dynamics.

PMID:36916902 | DOI:10.7554/eLife.79541

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A model of hippocampal replay driven by experience and environmental structure facilitates spatial learning

Elife. 2023 Mar 14;12:e82301. doi: 10.7554/eLife.82301. Online ahead of print.

ABSTRACT

Replay of neuronal sequences in the hippocampus during resting states and sleep play an important role in learning and memory consolidation. Consistent with these functions, replay sequences have been shown to obey current spatial constraints. Nevertheless, replay does not necessarily reflect previous behavior and can construct never-experienced sequences. Here we propose a stochastic replay mechanism that prioritizes experiences based on three variables: 1. Experience strength, 2. experience similarity, and 3. inhibition of return. Using this prioritized replay mechanism to train reinforcement learning agents leads to far better performance than using random replay. Its performance is close to the state-of-the-art, but computationally intensive, algorithm by Mattar & Daw (2018). Importantly, our model reproduces diverse types of replay because of the stochasticity of the replay mechanism and experience-dependent differences between the three variables. In conclusion, a unified replay mechanism generates diverse replay statistics and is efficient in driving spatial learning.

PMID:36916899 | DOI:10.7554/eLife.82301