Category: Nevin Manimala

Int Urogynecol J. 2022 Jun 14. doi: 10.1007/s00192-022-05261-y. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: We aimed to determine whether the presence of metabolic syndrome (MS) affects the efficacy of mirabegron in treatment-naïve women with overactive bladder (OAB).

METHODS: Women being treated with mirabegron 50 mg were allocated to MS and non-MS groups, and the efficacy of treatment of OAB was compared using the OAB symptom score (OABSS) and a 3-day voiding diary before and 12 weeks after starting treatment. The Wilcoxon signed-rank and Mann-Whitney U tests and multivariate logistic regression were used for statistical analyses, and a p-value < 0.05 was considered to represent statistical significance.

RESULTS: Of the 197 patients who completed the trial, 43 (23.9%) had MS. After 12 weeks of mirabegron treatment, both the MS and non-MS groups showed significant improvements in OABSS score, the number of incontinence episodes/24 h, the number of micturition episodes/24 h, and the number of episodes of urgency/24 h. The factors associated with clinically important differences in OABSS were the presence of hyperglycemia (odds ratio 2.43, 95% confidence interval [CI] 1.05-5.60) and OABSS score at baseline (odds ratio 1.23, 95% CI 1.09-1.39).

CONCLUSIONS: Mirabegron is effective in patients with and without MS, and comorbid hyperglycemia and severe OAB symptoms before treatment are predictors of the efficacy of mirabegron treatment.

PMID:35699775 | DOI:10.1007/s00192-022-05261-y

Int Orthop. 2022 Jun 14. doi: 10.1007/s00264-022-05471-5. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to investigate the clinical and radiological progression of the patients who underwent proximal fibular partial excision (PFPE) for medial compartment knee osteoarthritis.

METHODS: Patients with medial compartment knee osteoarthritis who did not benefit from conservative treatment and accepted the PFPE surgery were involved in this study. Patients with traumatic arthritis, inflammatory arthritis, previous lower extremity fractures, valgus malalignment of the knee, and infection at the planned surgical site, however, were kept apart. Patients were assessed both clinically by Visual Analog Scale (VAS) and American Knee Society Score (AKSS), radiologically by Kellgren Lawrence classification, tibiofemoral angle, and joint-line convergence angle (JLCA). The patients were systematically assessed especially in the sixth month and first, second, and third years of the post-operative period.

RESULTS: A total of 35 patients (mean age: 56.5, min: 45, max: 79) were involved in this study. The mean follow-up period was 22.4 months (min: 6, max: 36). It has been observed that: Statistically significant decrease in VAS and increase in AKSS after PFPE (p < 0.001) No statistically significant improvement in preoperative and postoperative tibiofemoral angle and JLCA measurements CONCLUSIONS: The PFPE is a safe and effective surgical treatment for pain relief and functional improvement in medial compartment knee osteoarthritis. More studies are needed on its mechanism of action, long-term effects, and comparison with other treatment options.

PMID:35699745 | DOI:10.1007/s00264-022-05471-5

Anal Bioanal Chem. 2022 Jun 14. doi: 10.1007/s00216-022-04118-z. Online ahead of print.

ABSTRACT

Non-targeted analysis (NTA) methods are widely used for chemical discovery but seldom employed for quantitation due to a lack of robust methods to estimate chemical concentrations with confidence limits. Herein, we present and evaluate new statistical methods for quantitative NTA (qNTA) using high-resolution mass spectrometry (HRMS) data from EPA’s Non-Targeted Analysis Collaborative Trial (ENTACT). Experimental intensities of ENTACT analytes were observed at multiple concentrations using a semi-automated NTA workflow. Chemical concentrations and corresponding confidence limits were first estimated using traditional calibration curves. Two qNTA estimation methods were then implemented using experimental response factor (RF) data (where RF = intensity/concentration). The bounded response factor method used a non-parametric bootstrap procedure to estimate select quantiles of training set RF distributions. Quantile estimates then were applied to test set HRMS intensities to inversely estimate concentrations with confidence limits. The ionization efficiency estimation method restricted the distribution of likely RFs for each analyte using ionization efficiency predictions. Given the intended future use for chemical risk characterization, predicted upper confidence limits (protective values) were compared to known chemical concentrations. Using traditional calibration curves, 95% of upper confidence limits were within ~tenfold of the true concentrations. The error increased to ~60-fold (ESI+) and ~120-fold (ESI-) for the ionization efficiency estimation method and to ~150-fold (ESI+) and ~130-fold (ESI-) for the bounded response factor method. This work demonstrates successful implementation of confidence limit estimation strategies to support qNTA studies and marks a crucial step towards translating NTA data in a risk-based context.

PMID:35699740 | DOI:10.1007/s00216-022-04118-z

JAMA. 2022 Jun 14;327(22):2201-2209. doi: 10.1001/jama.2022.8274.

ABSTRACT

IMPORTANCE: African American smokers have among the highest rates of tobacco-attributable morbidity and mortality in the US, and effective treatment is needed for all smoking levels.

OBJECTIVES: To evaluate the efficacy of varenicline vs placebo among African American adults who are light, moderate, and heavy daily smokers.

DESIGN, SETTING, AND PARTICIPANTS: The Kick It at Swope IV (KIS-IV) trial was a randomized, double-blind, placebo-controlled clinical trial conducted at a federally qualified health center in Kansas City. A total of 500 African American adults who were daily smokers of all smoking levels were enrolled from June 2015 to December 2017; final follow-up was completed in June 2018.

INTERVENTIONS: Participants were provided 6 sessions of culturally relevant individualized counseling and were randomized (in a 3:2 ratio) to receive varenicline (1 mg twice daily; n = 300) or placebo (n = 200) for 12 weeks. Randomization was stratified by sex and smoking level (1-10 cigarettes/d [light smokers] or >10 cigarettes/d [moderate to heavy smokers]).

MAIN OUTCOMES AND MEASURES: The primary outcome was salivary cotinine-verified 7-day point prevalence smoking abstinence at week 26. The secondary outcome was 7-day point prevalence smoking abstinence at week 12, with subgroup analyses for light smokers (1-10 cigarettes/d) and moderate to heavy smokers (>10 cigarettes/d).

RESULTS: Among 500 participants who were randomized and completed the baseline visit (mean age, 52 years; 262 [52%] women; 260 [52%] light smokers; 429 [86%] menthol users), 441 (88%) completed the trial. Treating those lost to follow-up as smokers, participants receiving varenicline were significantly more likely than those receiving placebo to be abstinent at week 26 (15.7% vs 6.5%; difference, 9.2% [95% CI, 3.8%-14.5%]; odds ratio [OR], 2.7 [95% CI, 1.4-5.1]; P = .002). The varenicline group also demonstrated greater abstinence than the placebo group at the end of treatment week 12 (18.7% vs 7.0%; difference, 11.7% [95% CI, 6.0%-17.7%]; OR, 3.0 [95% CI, 1.7-5.6]; P < .001). Smoking abstinence at week 12 was significantly greater for individuals receiving varenicline compared with placebo among light smokers (22.1% vs 8.5%; difference, 13.6% [95% CI, 5.2%-22.0%]; OR, 3.0 [95% CI, 1.4-6.7]; P = .004) and among moderate to heavy smokers (15.1% vs 5.3%; difference, 9.8% [95% CI, 2.4%-17.2%]; OR, 3.1 [95% CI, 1.1-8.6]; P = .02), with no significant smoking level × treatment interaction (P = .96). Medication adverse events were generally comparable between treatment groups, with nausea reported more frequently in the varenicline group (163 of 293 [55.6%]) than the placebo group (90 of 196 [45.9%]).

CONCLUSIONS AND RELEVANCE: Among African American adults who are daily smokers, varenicline added to counseling resulted in a statistically significant improvement in the rates of 7-day point prevalence smoking abstinence at week 26 compared with counseling and placebo. The findings support the use of varenicline in addition to counseling for tobacco use treatment among African American adults who are daily smokers.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02360631.

PMID:35699705 | DOI:10.1001/jama.2022.8274

Stat Med. 2022 Mar 17. doi: 10.1002/sim.9376. Online ahead of print.

ABSTRACT

The article develops marginal models for multivariate longitudinal responses. Overall, the model consists of five regression submodels, one for the mean and four for the covariance matrix, with the latter resulting by considering various matrix decompositions. The decompositions that we employ are intuitive, easy to understand, and they do not rely on any assumptions such as the presence of an ordering among the multivariate responses. The regression submodels are semi-parametric, with unknown functions represented by basis function expansions. We use spike-slap priors for the regression coefficients to achieve variable selection and function regularization, and to obtain parameter estimates that account for model uncertainty. An efficient Markov chain Monte Carlo algorithm for posterior sampling is developed. The simulation study presented investigates the gains that one may have when considering multivariate longitudinal analyses instead of univariate ones, and whether these gains can counteract the negative effects of missing data. We apply the methods on a highly unbalanced longitudinal dataset with four responses observed over a period of 20 years.

PMID:35699116 | DOI:10.1002/sim.9376

Stat Med. 2022 Mar 14. doi: 10.1002/sim.9373. Online ahead of print.

ABSTRACT

The mixture cure model for analyzing survival data is characterized by the assumption that the population under study is divided into a group of subjects who will experience the event of interest over some finite time horizon and another group of cured subjects who will never experience the event irrespective of the duration of follow-up. When using the Bayesian paradigm for inference in survival models with a cure fraction, it is common practice to rely on Markov chain Monte Carlo (MCMC) methods to sample from posterior distributions. Although computationally feasible, the iterative nature of MCMC often implies long sampling times to explore the target space with chains that may suffer from slow convergence and poor mixing. Furthermore, extra efforts have to be invested in diagnostic checks to monitor the reliability of the generated posterior samples. A sampling-free strategy for fast and flexible Bayesian inference in the mixture cure model is suggested in this article by combining Laplace approximations and penalized B-splines. A logistic regression model is assumed for the cure proportion and a Cox proportional hazards model with a P-spline approximated baseline hazard is used to specify the conditional survival function of susceptible subjects. Laplace approximations to the posterior conditional latent vector are based on analytical formulas for the gradient and Hessian of the log-likelihood, resulting in a substantial speed-up in approximating posterior distributions. The spline specification yields smooth estimates of survival curves and functions of latent variables together with their associated credible interval are estimated in seconds. A fully stochastic algorithm based on a Metropolis-Langevin-within-Gibbs sampler is also suggested as an alternative to the proposed Laplacian-P-splines mixture cure (LPSMC) methodology. The statistical performance and computational efficiency of LPSMC is assessed in a simulation study. Results show that LPSMC is an appealing alternative to MCMC for approximate Bayesian inference in standard mixture cure models. Finally, the novel LPSMC approach is illustrated on three applications involving real survival data.

PMID:35699121 | DOI:10.1002/sim.9373

Int Rev Psychiatry. 2022 Feb 17;34(2):128-139. doi: 10.1080/09540261.2022.2061840. Epub 2022 May 22.

ABSTRACT

Increases in youth psychiatric presentations to out-patient and emergency department settings during COVID-19 have been reported. This study, using data from five hospitals in Ireland, examines changes in the number and type of paediatric admissions during COVID-19 (March 2020 – February 2021) compared to the previous two years. ICD-10 classification was used to establish admissions with mental, behavioural, neuro-developmental disorders and psychosocial reasons (MBN-PS). Overall hospital admissions fell by 25.3%, while MBN-PS fell by only 2.6%, mostly during an initial lockdown. Admissions for MBN-PS increased in July-August (9.2%), increased further in September-December (28.3%), returning to pre-COVID-19 levels in January-February 2021. Significant increases were observed among youths with anorexia nervosa (47.8%), other eating disorders (42.9%), and admissions for anxiety (29.6%), with these effects relating to females only. Although admissions for self-harm increased (3%) and rates of ASD admissions reduced (17%), these were not statistically significant. The disproportionate increase in admissions for MBN-PS compared to medical admissions suggests an adverse effect of COVID-19 on youth mental health, for females in particular, and supports previous reports of a pandemic specific increase in eating psychopathology. Combined community and acute service delivery and capacity planning are urgently needed given the prior underfunding of services pre-pandemic.

PMID:35699100 | DOI:10.1080/09540261.2022.2061840

Int Rev Psychiatry. 2022 Feb 17;34(2):154-167. doi: 10.1080/09540261.2022.2072193. Epub 2022 May 12.

ABSTRACT

Chromatin remodelling is an important process in neural development and is related to autism spectrum disorder (ASD) and schizophrenia (SCZ) aetiology. To further elucidate the involvement of chromatin remodelling genes in the genetic aetiology of ASD and SCZ in the Japanese population, we performed a case-control study. Targeted sequencing was conducted on coding regions of four BAF chromatin remodelling complex genes: SMARCA2, SMARCA4, SMARCC2, and ARID1B in 185 ASD, 432 SCZ patients, and 517 controls. 27 rare non-synonymous variants were identified in ASD and SCZ patients, including 25 missense, one in-frame deletion in SMRACA4, and one frame-shift variant in SMARCC2. Association analysis was conducted to investigate the burden of rare variants in BAF genes in ASD and SCZ patients. Significant enrichment of rare missense variants in BAF genes, but not synonymous variants, was found in ASD compared to controls. Rare pathogenic variants indicated by in silico tools were significantly enriched in ASD, but not statistically significant in SCZ. Pathogenic-predicted variants were located in disordered binding regions and may confer risk for ASD and SCZ by disrupting protein-protein interactions. Our study supports the involvement of rare missense variants of BAF genes in ASD and SCZ susceptibility.

PMID:35699097 | DOI:10.1080/09540261.2022.2072193

Clin Exp Rheumatol. 2022 Jun 13. doi: 10.55563/clinexprheumatol/077ul6. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the effect of potential confounders on the association between sex and disease impact in recent-onset psoriatic arthritis.

METHODS: We performed a multicentre observational prospective study (2-year follow-up, regular annual visits). The study population comprised patients aged ≥18 years who fulfilled the CASPAR criteria and less than 2 years since the onset of symptoms. The dataset was generated using data for each patient at the 3 visits (baseline, first year, and second year of follow-up) matched with the PsAID values at each of the 3 visits. Once variables associated with both PsAID ≥4 and sex were selected, those that led to a difference of >10% between the adjusted and crude estimations were identified as potential confounders in the association between sex and PsAID. Lastly, the final multivariate logistic regression model estimating the association between sex and PsAID was defined.

RESULTS: The dataset contained 418 observations (158 at baseline, 135 at the first follow-up visit, and 125 at the second visit). The confounders identified in the multivariate model were HAQ, global pain, level of physical activity, and joint pattern at diagnosis. After adjustment for these variables, no statistically significant association was observed between female sex and PsAID ≥4.

CONCLUSIONS: The association between female sex and greater disease impact could be explained by the influence of other variables, specifically higher HAQ score, greater intensity of pain, differences in the level of physical activity and in the joint pattern at diagnosis (lower frequency of the spondylitis pattern in women).

PMID:35699067 | DOI:10.55563/clinexprheumatol/077ul6

J Endourol. 2022 Jun 14. doi: 10.1089/end.2021.0811. Online ahead of print.

ABSTRACT

INTRODUCTION: For treatment of nephrolithiasis, ambulatory percutaneous nephrolithotomy (aPCNL) is growing in popularity for select patients. The aim of this study was to investigate the safety and efficacy of a set of aPCNL selection criteria as well as search for predictors of failed aPCNL resulting in inpatient admission.

METHODS AND MATERIALS: We reviewed all PCNL patients from 2016-2020. A total of 175 met selection criteria for aPCNL and were included. Primary outcome was safety and efficacy, and secondary outcome was to identify predictors of inpatient stay. Demographic and peri-operative data were analyzed with both descriptive and inferential statistics.

RESULTS: In total, between 2016-2020, 552 patients underwent PCNL, with 175 of them meeting criteria for aPCNL. 134/175 (76.6%) of these patients were successfully discharged the same day as the surgery and 41 patients were admitted. On univariate analysis, patients who required upper pole access or multiple accesses, (p=0.038) ASA>2 (p=0.005), or postoperative nephrostomy tube (PCN) (p<0.001) were more likely to be admitted after surgery. On multivariate analysis, only postoperative PCN was significantly associated with admission (p=0.015). Regarding reasons for unsuccessful aPCNL, 19.5% of admissions were attributed to intraoperative complications, 7% to social causes, 12.2% to postoperative complications, 14.6% to uncontrolled pain, and 34.1% to unexpected intraoperative procedures.

CONCLUSIONS: Ambulatory PCNL using selection criteria is safe and effective, with postoperative PCN predicting the possible necessity for conversion to inpatient admission. Furthermore, our study provides a practical algorithm for those opting to provide ambulatory PCNL to patients.

PMID:35699065 | DOI:10.1089/end.2021.0811