Category: Nevin Manimala

Eur Urol. 2022 Apr 21:S0302-2838(22)01802-4. doi: 10.1016/j.eururo.2022.03.031. Online ahead of print.

ABSTRACT

CONTEXT: Several recent randomised trials have evaluated the role of combination systemic treatment using androgen deprivation therapy (ADT) plus chemotherapy or an androgen receptor signaling inhibitor (ARSI) in patients with high-risk and/or unfavourable nonmetastatic prostate cancer (nmPC).

OBJECTIVE: To assess the outcomes associated with adding combination systemic treatment to primary definitive local therapy in patients with high-risk and/or unfavourable nmPC.

EVIDENCE ACQUISITION: We queried the PubMed, Web of Science, and Scopus databases and conference abstracts to identify prospective randomised trials examining the value of adding chemotherapy or an ARSI to ADT and primary local therapy with curative intent for nmPC. The primary endpoints were overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), and failure-free survival (FFS). Secondary endpoints included adverse events (AEs) and pathologic outcomes.

EVIDENCE SYNTHESIS: We identified 15 randomised studies, of which nine evaluated chemohormonal and six investigated ARSI-based treatment strategies. In both radical prostatectomy (RP) and radiation therapy (RT) settings, addition of docetaxel to ADT was associated with significantly better CSS (pooled hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.49-0.95; p = 0.025), MFS (pooled HR 0.82, 95% CI 0.71-0.95; p = 0.008), and FFS (pooled HR 0.70, 95% CI 0.62-0.79; p < 0.001); the difference did not meet the conventional level of statistical significance for OS (pooled HR 0.86, 95% CI 0.73-1.01; p = 0.072). For patients treated with RT alone, docetaxel-based combination treatment did not meet the significance threshold set for OS (p = 0.3), CSS (p = 0.072), or MFS (p = 0.079), but the difference for FFS was statistically significant (pooled HR 0.72, 95% CI 0.63-0.84; p < 0.001). On network meta-analyses including RT studies, ARSI + ADT outperformed docetaxel + ADT for survival endpoints and had a more favourable AE profile.

CONCLUSIONS: Intensification of systemic therapy with docetaxel or an ARSI in addition to ADT improves oncologic endpoints in high-risk and/or unfavourable nmPC treated with local definitive therapy. The highest efficacy was achieved with ARSI + ADT, specifically in patients treated with RT.

PATIENT SUMMARY: Our findings highlight that selected patients with high-risk nonmetastatic prostate cancer benefit from intensification of systemic therapy beyond hormonal treatment.

PMID:35465985 | DOI:10.1016/j.eururo.2022.03.031

Vaccine. 2022 Apr 18:S0264-410X(22)00474-1. doi: 10.1016/j.vaccine.2022.04.046. Online ahead of print.

ABSTRACT

BACKGROUND: Short-term side effects related to mRNA vaccines against SARS-CoV-2 are frequent and bothersome, with the potential to disrupt work duties and impact future vaccine decision-making.

OBJECTIVE: To identify factors more likely to lead to vaccine-associated work disruption, employee absenteeism, and future vaccine reluctance among healthcare workers (HCWs).

HYPOTHESIS: Side effects related to COVID vaccination: 1- frequently disrupt HCW duties, 2- result in a significant proportion of HCW absenteeism, 3- contribute to uncertainty about future booster vaccination, 4- vary based on certain demographic, socioeconomic, occupational, and vaccine-related factors.

METHODS: Using an anonymous, voluntary electronic survey, we obtained responses from a large, heterogeneous sample of COVID-19-vaccinated HCWs in two healthcare systems in Southern California. Descriptive statistics and regression models were utilized to evaluate the research questions.

RESULTS: Among 2,103 vaccinated HCWs, 579 (27.5%) reported that vaccine-related symptoms disrupted their professional responsibilities, and 380 (18.1%) missed work as a result. Independent predictors for absenteeism included experiencing generalized and work-disruptive symptoms, and receiving the Moderna vaccine [OR = 1.77 (95% CI = 1.33 – 2.36), p < 0.001]. Physicians were less likely to miss work due to side effects (6.7% vs 21.2% for all other HCWs, p < 0.001). Independent predictors of reluctance toward future booster vaccination included lower education level, younger age, having received the Moderna vaccine, and missing work due to vaccine-related symptoms.

CONCLUSION: Symptoms related to mRNA vaccinations against SARS-CoV-2 may frequently disrupt work duties, lead to absenteeism, and impact future vaccine decision-making. This may be more common in Moderna recipients and less likely among physicians. Accordingly, health employers should schedule future booster vaccination cycles to minimize loss of work productivity.

PMID:35465979 | DOI:10.1016/j.vaccine.2022.04.046

J Prosthet Dent. 2022 Apr 21:S0022-3913(22)00200-1. doi: 10.1016/j.prosdent.2022.03.020. Online ahead of print.

ABSTRACT

STATEMENT OF PROBLEM: The disinfection of removable dental prostheses and orthodontic appliances is essential to preventing transmission of pathogens. However, whether different disinfection solutions and durations affect the physical properties of denture base resins is unclear.

PURPOSE: The purpose of this systematic review and meta-analysis was to statistically analyze the influence of disinfectants on the physical properties of denture base resins.

MATERIAL AND METHODS: A systematic search in Medline, Embase, PubMed, and Cochrane Library databases was conducted to evaluate the effects of chemical disinfection on the physical properties of denture base resins such as surface morphology, roughness, hardness, and flexural strength. Of 1909 studies, 44 studies were included in the systematic review and 41 in the meta-analysis. Heterogeneity was analyzed by using I² statistics. The influence of different disinfection solutions and durations on the physical properties was further analyzed, and the risk of bias evaluated. Statistical analyses were performed by using the RevMan 5.4 software program with the standardized mean differences (SMDs) and 95% confidence intervals (CIs).

RESULTS: Of the 44 included studies, 40 studies were assessed as having a low risk of bias, and 4 had an unclear risk of bias. Meta-analysis results showed that compared with the control, disinfection could not significantly affect surface roughness and hardness within 60 minutes of immersion in disinfectant solutions or flexural strength within 30 minutes (roughness: P=.79, I²=0%; flexural strength: P=.08, I²=0%; hardness: P=.05, I²=19%). In addition, the physical properties were not significantly affected when glutaraldehyde, chlorhexidine, and peracetic acid were repeatedly used for more than 30 minutes.

CONCLUSIONS: Most of the disinfectants did not reduce the physical properties of denture base resin within 30 minutes of immersion. Glutaraldehyde, chlorhexidine, and peracetic acid are recommended if longer immersion or repeated disinfection is required.

PMID:35465961 | DOI:10.1016/j.prosdent.2022.03.020

Neurologia (Engl Ed). 2022 Apr;37(3):199-215. doi: 10.1016/j.nrleng.2020.05.004. Epub 2020 May 24.

ABSTRACT

INTRODUCTION: A growing number of studies have evaluated the effects of transcranial magnetic stimulation (TMS) for the symptomatic treatment of multiple sclerosis (MS).

METHODS: We performed a PubMed search for articles, recent books, and recommendations from the most relevant clinical practice guidelines and scientific societies regarding the use of TMS as symptomatic treatment in MS.

CONCLUSIONS: Excitatory electromagnetic pulses applied to the affected cerebral hemisphere allow us to optimise functional brain activity, including the transmission of nerve impulses through the demyelinated corticospinal pathway. Various studies into TMS have safely shown statistically significant improvements in spasticity, fatigue, lower urinary tract dysfunction, manual dexterity, gait, and cognitive deficits related to working memory in patients with MS; however, the exact level of evidence has not been defined as the results have not been replicated in a sufficient number of controlled studies. Further well-designed, randomised, controlled clinical trials involving a greater number of patients are warranted to attain a higher level of evidence in order to recommend the appropriate use of TMS in MS patients across the board. TMS acts as an adjuvant with other symptomatic and immunomodulatory treatments. Additional studies should specifically investigate the effect of conventional repetitive TMS on fatigue in these patients, something that has yet to see the light of day.

PMID:35465914 | DOI:10.1016/j.nrleng.2020.05.004

Br J Anaesth. 2022 Apr 21:S0007-0912(22)00139-8. doi: 10.1016/j.bja.2022.03.015. Online ahead of print.

ABSTRACT

BACKGROUND: Preoperative frailty may predispose patients to poorer outcomes in cardiac surgery; however, there are limited data concerning how preoperative frailty predicts patient-centred outcomes, such as patient-reported disability. Our objective was to evaluate the association between preoperative frailty and postoperative disability.

METHODS: Patients were prospectively evaluated using the Comprehensive Assessment of Frailty score, separating patients into frail and non-frail cohorts. Disability levels were quantified using the WHO Disability Assessment Schedule (WHODAS) 2.0 in percentage of the maximum disability score, with disability defined as a value ≥25%.

RESULTS: Frail patients had increased median [inter-quartile range] disability scores of 31 [16-45]% preoperatively, 29 [9-54]% at 1 month, and 15 [3-31]% at 3 months postoperatively, compared with disability scores in non-frail patients of 10 [5-17]%, 17 [6-29]%, and 2.1 [0-12.0]%, respectively. Preoperative frailty was associated with a reduced likelihood of patients being free of disability and alive at 3 months; adjusted odds ratio 0.51 (for age, European System for Cardiac Operative Risk Evaluation II, and WHODAS 2.0: 12-Part Questionnaire score); P=0.045. The trajectory of disability scores, assessed in percentage change from the preoperative baseline, showed non-frail patients had increased disability burden at 1 month, whereas frail patients had reduced disability burden (+4.2% vs -2.1%; P=0.04). Although the disability burden decreased for both groups at 3 months, this was most marked for frail patients (-6.3% vs -10.4%; P=0.02).

CONCLUSIONS: Disability burden in frail patients improves continuously postoperatively, whereas in non-frail patients, it worsens at 1 month before improving at 3 months postoperatively. This positive trajectory of patient-centred outcomes in frail patients should be considered in preoperative decision-making.

PMID:35465950 | DOI:10.1016/j.bja.2022.03.015

Neurologia (Engl Ed). 2022 Apr;37(3):171-177. doi: 10.1016/j.nrleng.2019.03.017. Epub 2021 Apr 6.

ABSTRACT

INTRODUCTION: Epilepsy is most frequent in children and elderly people. Today’s population is ageing and epilepsy prevalence is increasing. The type of epilepsy and its management change with age.

METHODS: We performed a retrospective, observational study comparing patients aged ≥ 65 years with epilepsy diagnosed before and after the age of 65, and describing epilepsy characteristics and comorbidities in each group.

RESULTS: The sample included 123 patients, of whom 61 were diagnosed at < 65 years of age (group A), 62 at ≥ 65 of age (group B). Sex distribution was similar in both groups, with 39 men (62.9%) in group A and 37 (60.7%) in group B. Mean age was 69.97 ± 5.6 years in group A and 77.29 ± 6.73 in group B. The most common aetiology was cryptogenic in group A (44.3%, n = 27) and vascular in group B (74.2%, n = 46). History of stroke was present in 12 patients from group A (19.7%) and 32 (51.6%) in group B. Antiepileptic drugs were prescribed at lower doses in group A. Statistically significant differences were found between groups for history of ischaemic stroke, cognitive impairment, psychiatric disorders, and diabetes mellitus; degree of dependence; and number of antiepileptic drugs.

CONCLUSION: Age of onset ≥ 65 years is closely related to cardiovascular risk factors; these patients require fewer antiepileptic drugs and respond to lower doses. Some cases initially present as status epilepticus.

PMID:35465910 | DOI:10.1016/j.nrleng.2019.03.017

Epidemiol Infect. 2022 Apr 25:1-20. doi: 10.1017/S0950268822000747. Online ahead of print.

NO ABSTRACT

PMID:35465866 | DOI:10.1017/S0950268822000747

Infect Control Hosp Epidemiol. 2022 Apr 25:1-8. doi: 10.1017/ice.2022.82. Online ahead of print.

ABSTRACT

BACKGROUND: Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy.

OBJECTIVE: To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML.

METHODS: We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics.

RESULTS: The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75-1.32) and TIC IRR = 0.83 (95% CI, 0.49-1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar.

CONCLUSIONS: In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.

PMID:35465865 | DOI:10.1017/ice.2022.82

Prep Biochem Biotechnol. 2022 Apr 23:1-16. doi: 10.1080/10826068.2022.2056746. Online ahead of print.

ABSTRACT

A non-segregated kinetic model is proposed to describe a fermentation process of agro-industrial residues derived via cocoa (mucilage juice) by Pichia kudriavzevii. The novel proposed hybrid model is based on a multiple coupling reaction mechanisms (structured) to describe the kinetics of substrate consumption, biomass, carbon dioxide, and ethanol, coupled to an unstructured model for the activity enzyme. The parameters of the kinetic model are estimated by non-linear least-squares curve fitting using the Marquardt-Levenberg algorithm. In addition, numerical simulations were compared with the experimental data via residual graphs. The effectiveness of the model was statistically evaluated using dimensionless efficiency coefficients under different initial conditions. A global sensitivity analysis was applied (Fisher’s information matrix). The experimental results of the batch reactor showed a maximum ethanol concentration of 29 g/L, with a yield of 0.48 g-ethanol/g-glucose and a productivity of 0.30 g/L h. The method determined that the cell formation coefficient and the specific substrate consumption rate (θ1 and θ2) directly influence most of the states of our system. The proposed scheme is particularly suitable to assist in the rational design of cell factory properties or fermentation processes because it can represent the complex biochemistry in more detail and under different initial experimental conditions; the above reveals that the generated model is robust and can be considered for control and optimization purposes.

PMID:35465843 | DOI:10.1080/10826068.2022.2056746

J Int Neuropsychol Soc. 2022 Apr 25:1-11. doi: 10.1017/S1355617722000169. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine associations of alcohol use with cognitive aging among middle-aged men.

METHOD: 1,608 male twins (mean 57 years at baseline) participated in up to three visits over 12 years, from 2003-2007 to 2016-2019. Participants were classified into six groups based on current and past self-reported alcohol use: lifetime abstainers, former drinkers, very light (1-4 drinks in past 14 days), light (5-14 drinks), moderate (15-28 drinks), and at-risk drinkers (>28 drinks in past 14 days). Linear mixed-effects regressions modeled cognitive trajectories by alcohol group, with time-based models evaluating rate of decline as a function of baseline alcohol use, and age-based models evaluating age-related differences in performance by current alcohol use. Analyses used standardized cognitive domain factor scores and adjusted for sociodemographic and health-related factors.

RESULTS: Performance decreased over time in all domains. Relative to very light drinkers, former drinkers showed worse verbal fluency performance, by -0.21 SD (95% CI -0.35, -0.07), and at-risk drinkers showed faster working memory decline, by 0.14 SD (95% CI 0.02, -0.20) per decade. There was no evidence of protective associations of light/moderate drinking on rate of decline. In age-based models, light drinkers displayed better memory performance at advanced ages than very light drinkers (+0.14 SD; 95% CI 0.02, 0.20 per 10-years older age); likely attributable to residual confounding or reverse association.

CONCLUSIONS: Alcohol consumption showed minimal associations with cognitive aging among middle-aged men. Stronger associations of alcohol with cognitive aging may become apparent at older ages, when cognitive abilities decline more rapidly.

PMID:35465863 | DOI:10.1017/S1355617722000169