Nevin Manimala

Urology. 2022 Jan 23:S0090-4295(22)00070-X. doi: 10.1016/j.urology.2022.01.020. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine practice-level variation in the management of MRI PI-RADS 3 lesions in men with favorable-risk prostate cancer (FRPC) considering or on active surveillance (AS).

METHODS: We reviewed the MUSIC registry for FRPC men (GG1 and low-volume GG2) undergoing MRI from 1/2013-3/2020. The primary outcome was to assess practice-level variation in time from MRI to biopsy and MRI to treatment for PI-RADS 3 lesions. Both MRIs obtained after the diagnostic biopsy and while on AS were included. The Kaplan-Meier method was used to estimate biopsy-free survival for time from MRI to surveillance biopsy and multivariable Cox proportional hazards models identified clinical and demographic factors associated with time obtaining a biopsy after finding PI-RADS 3 lesions.

RESULTS: We identified 3,172 FRPC men with a MRI, of whom 473 had a PI-RADS 3. There was significant practice-level variation in biopsy rates among patients with PI-RADS 3 MRI results (log-rank test, p<0.001), with biopsy-free probability at 6 months ranging from 28%-69% (median: 59%). We were unable to identify factors with significant associations with time to biopsy. Conversely, there was less variation in time from PI-RADS 3 to treatment (log-rank test, p=0.2), while several clinical factors had statistically-significant associations: age(p=0.018), PSA-Density 0.1-0.2(p=0.035), ISUP-GG 2(p=0.002), and number of positive cores(p<0.001), as expected.

CONCLUSION: Urology practice, rather than GG or extent of biopsy positivity, is the largest factor affecting the decision for biopsy of PI-RADS 3 lesions in FRPC men considering or on AS. Future work to assist with decision-making and reduce variability is needed.

PMID:35081398 | DOI:10.1016/j.urology.2022.01.020

Annu Rev Phys Chem. 2022 Jan 26. doi: 10.1146/annurev-physchem-090519-045916. Online ahead of print.

ABSTRACT

We review a suite of stochastic vector computational approaches for studying the electronic structure of extended condensed matter systems. These techniques help reduce algorithmic complexity, facilitate efficient parallelization, simplify computational tasks, accelerate calculations, and diminish memory requirements. While their scope is vast, we limit our study to ground-state and finite temperature density functional theory (DFT) and second-order perturbation theory. More advanced topics, such as quasiparticle (charge) and optical (neutral) excitations and higher-order processes, are covered elsewhere. We start by explaining how to use stochastic vectors in computations, characterizing the associated statistical errors. Next, we show how to estimate the electron density in DFT and discuss highly effective techniques to reduce statistical errors. Finally, we review the use of stochastic vector techniques for calculating correlation energies within the second-order Møller-Plesset perturbation theory and its finite temperature variational form. Example calculation results are presented and used to demonstrate the efficacy of the methods. Expected final online publication date for the Annual Review of Physical Chemistry, Volume 73 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID:35081326 | DOI:10.1146/annurev-physchem-090519-045916

Annu Rev Phys Chem. 2022 Jan 26. doi: 10.1146/annurev-physchem-082620-021809. Online ahead of print.

ABSTRACT

This review focuses on a recent class of path-integral-based methods that simulate nonadiabatic dynamics in the condensed phase using only classical molecular dynamics trajectories in an extended phase space. Specifically, a semiclassical mapping protocol is used to derive an exact, continuous, Cartesian variable path-integral representation for the canonical partition function of a system in which multiple electronic states are coupled to nuclear degrees of freedom. Building on this exact statistical foundation, multistate ring polymer molecular dynamics methods are developed for the approximate calculation of real-time thermal correlation functions. The remarkable promise of these multistate ring polymer methods, their successful applications, and their limitations are discussed in detail.Expected final online publication date for the Annual Review of Physical Chemistry, Volume 73 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID:35081325 | DOI:10.1146/annurev-physchem-082620-021809

N Engl J Med. 2022 Jan 26. doi: 10.1056/NEJMoa2116414. Online ahead of print.

ABSTRACT

BACKGROUND: Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients.

METHODS: In this phase 1-2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 μg, Ad26.COV2.S (Johnson & Johnson-Janssen) at a dose of 5×10¹⁰ virus particles, or BNT162b2 (Pfizer-BioNTech) at a dose of 30 μg. The primary end points were safety, reactogenicity, and humoral immunogenicity on trial days 15 and 29.

RESULTS: Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients.

CONCLUSIONS: Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209.).

PMID:35081293 | DOI:10.1056/NEJMoa2116414

J Clin Psychiatry. 2022 Jan 25;83(1):22f14388. doi: 10.4088/JCP.22f14388.

ABSTRACT

During the past decade, nearly a dozen small and large, prospective and retrospective observational studies examined cognitive neurodevelopmental outcomes in childhood after gestational exposure to antidepressant drugs. Many of the studies found that exposure was associated with poorer outcomes on measures of language, cognition, intellectual skills, and academic performance, but, in most instances, the association appeared to be more related to maternal depression during pregnancy and other confounds than to antidepressant use during pregnancy. A large new population-based observational study specifically examined language and mathematics performance in serial, nationally standardized tests. The study found that, in fully adjusted analyses, in children and adolescents aged 9-15 years, a history of gestational exposure to antidepressant drugs was associated with a small (by about 2 out of 100 points) but statistically significantly poorer performance in mathematics but not in language. The findings were consistent though attenuated in a large number of important and appropriate sensitivity analyses, some of which adjusted for confounding in additional ways. The body of literature reviewed suggests that prenatal antidepressant exposure is indeed associated with cognitive neurodevelopmental deficits and that the deficits are attenuated or eliminated by adjustment for maternal depression and other confounds. It is suggested that the deficits that remain despite adjustment may be due to residual confounding from unmeasured behavioral and internal environment variables associated with untreated maternal depression. Thus, prenatal antidepressant exposure may merely be a marker rather than the cause of cognitive neurodevelopmental deficits. Whereas the literature in the field does not drive a case for withholding antidepressants from depressed pregnant women, decision-making must remain a shared process.

PMID:35081278 | DOI:10.4088/JCP.22f14388

Clin Respir J. 2022 Jan 26. doi: 10.1111/crj.13474. Online ahead of print.

ABSTRACT

Patients with severe eosinophilic asthma experience daily activity limitations and reduced productivity at work. Using anonymized individual patient-level data from two previously conducted randomized, double-blind, placebo-controlled studies (MENSA [GSK ID:115588/NCT01691521]; MUSCA [GSK ID:200862/NCT02281318]), we investigated the effect of mepolizumab on work productivity, activity limitation, symptoms, and rescue medication use. Patient-reported outcomes including Work Productivity and Activity Impairment-General Health (WPAI-GH) scores (impairment percentages, 0%-100%), global activity limitation (scale 1-4), and perceived change in activity limitation (Likert scale 1-7) since the start of the study were analyzed. WPAI-GH scores from MENSA were analyzed post hoc for employed patients using mixed model repeated measures; global activity limitation and perceived change in activity limitation from MUSCA were analyzed by ordinal logistic regression. Mean changes from baseline in daily asthma symptom scores (scale 0-5) and rescue medication use (occasions/day) were also assessed, via a post hoc meta-analysis of MENSA and MUSCA. At study end, WPAI-GH scores indicative of overall work impairment, impairment while working, and activity impairment consistently improved with mepolizumab versus placebo. Overall, 76% versus 54% of patients rated their activity as “much better,” “better,” or “slightly better” since the start of the study with mepolizumab versus placebo. Mepolizumab was associated with numerically larger improvements from baseline in asthma symptoms (treatment difference 0.21-0.29 points) and rescue medication use (treatment difference -0.08 to -0.22 occasions/day) versus placebo. Our results indicate that patients with severe eosinophilic asthma may experience improved activity limitation, work productivity, symptoms, and rescue medication use with mepolizumab.

PMID:35081275 | DOI:10.1111/crj.13474

Clin Respir J. 2022 Jan 26. doi: 10.1111/crj.13476. Online ahead of print.

ABSTRACT

INTRODUCTION: Many confounding factors such as sex, age, and body mass index (BMI) affect pulmonary function parameters, but there are limited data about the direct and/or indirect effects of small airway function on lung function for differences in confounding factors.

OBJECTIVES: This study aimed to use structural equation model (SEM) to explain the influence of the confounding factors (age, sex, and BMI) on the relationship between small airway function and lung function in patients with lung cancer.

METHODS: A cross-sectional observational study was conducted in a single medical center. Subjects were assessed; small airway function was specified by MEF25% and MEF50%; lung function by FVC; pulmonary obstruction by FEV1, FEV1%, and FEV1/FVC; and PEF and PEF% reflected the strength of abdominal muscles. The measurement model was analyzed by confirmatory factor analysis. The SEM was conducted to analyze the structural models of the effects of the confounding factors.

RESULTS: In the measurement model, variables were fit to their domains, the path linking age and sex to pulmonary obstruction was positive and statistically significant, and the path linking sex to muscle strength was also positive and statistically significant. Muscle strength positively and significantly mediates the path between sex and FVC. As a moderator, BMI increased the effects of small airway function on FVC.

CONCLUSION: Age and sex were directed to pulmonary obstruction, and muscle strength as a mediator between sex and lung function was novel, and BMI adjusted the effects of small airway function on FVC.

PMID:35081274 | DOI:10.1111/crj.13476

J Magn Reson Imaging. 2022 Jan 26. doi: 10.1002/jmri.28069. Online ahead of print.

ABSTRACT

BACKGROUND: The diagnosis of labral injury on MRI is time-consuming and potential for incorrect diagnoses.

PURPOSE: To explore the feasibility of applying deep learning to diagnose and classify labral injuries with MRI.

STUDY TYPE: Retrospective.

POPULATION: A total of 1016 patients were divided into normal (n = 168, class 0) and abnormal labrum (n = 848) groups. The abnormal group consisted of n = 111 with class 1 (degeneration), n = 437 with class 2 (partial or complete tear), and n = 300 with unclassified injury. Patients were randomly divided into training, validation, and test cohort according to the ratio of 55%:15%:30%.

FIELD STRENGTH/SEQUENCE: Fat-saturation proton density-weighted fast spin-echo sequence at 3.0 T.

ASSESSMENT: Convolutional neural network-6 (CNN-6) was used to extract, discriminate, and detect oblique coronal (OCOR) and oblique sagittal (OSAG) images. Mask R-CNN was used for segmentation. LeNet-5 was used to diagnose and classify labral injuries. The weighting method combined the models of OCOR and OSAG. The output-input connection was used to correlate the whole diagnosis/classification system. Four radiologists performed subjective diagnoses to obtain the diagnosis results.

STATISTICAL TESTS: CNN-6 and LeNet-5 were evaluated by area under the receiver operating characteristic (ROC) curve and related parameters. The mean average precision (MAP) evaluated the Mask R-CNN. McNemar’s test was used to compare the radiologists and models. A P value < 0.05 was considered statistically significant.

RESULTS: The area under the curve (AUC) of CNN-6 was 0.99 for extraction, discrimination, and detection. MAP values of Mask R-CNN for OCOR and OSAG image segmentation were 0.96 and 0.99. The accuracies of LeNet-5 in the diagnosis and classification were 0.94/0.94 (OCOR) and 0.92/0.91 (OSAG), respectively. The accuracy of the weighted models in the diagnosis and classification were 0.94 and 0.97, respectively. The accuracies of radiologists in the diagnosis and classification of labrum injuries ranged from 0.85 to 0.92 and 0.78 to 0.94, respectively.

DATA CONCLUSION: Deep learning can assist radiologists in diagnosing and classifying labrum injuries.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

PMID:35081273 | DOI:10.1002/jmri.28069

Clin Respir J. 2022 Jan 26. doi: 10.1111/crj.13469. Online ahead of print.

ABSTRACT

OBJECTIVE: Balance and cognitive problems may develop in COPD. Studies investigating cognitive functions are mostly in elderly patients, and the number of studies on balance impairment is less than studies about cognitive dysfunction in COPD. We aimed to evaluate both balance and cognitive functions in patients with COPD under 65 years.

METHODS: A total of 60 COPD patients and 60 healthy control group were enrolled. The patients with COPD were divided into two groups due to dyspnea severity. Demographic data and dyspnea scores of all patients were recorded. BECK depression scale, standardized Mini Mental Test (MMT), and BERG balance scale were applied to the individuals. Factors affecting BERG balance scale were evaluated.

RESULTS: BERG balance scale and MMT values were found to be significantly lower in patients with COPD compared with the control group (p = 0.009). It was observed that the mean values of BERG balance scale and MMT were significantly low in the severe dyspnea group. BERG scale had significant correlations with MMT (rho = 0.331, p = 0.001), BECK (rho = -0.222, p = 0.016), age (rho = -0.318, p = 0.018), MMRC (rho = -0.368, p < 0.001), CAT (rho = -0.338, p = 0.008), FEV1% (rho = 0.307, p = 0.017), SpO₂ (rho = 0.448, p < 0.001), and number of hospitalization per year (rho = -0.316, p = 0.014). According to the results of multiple linear regression analysis, the effect of oxygen saturation on BERG was found to be statistically significant (B = 0.512, p = 0.008).

CONCLUSIONS: Balance tests in patients with COPD under the age of 65 are significantly low when compared with healthy controls at the same age. Balance and cognitive functions are significantly associated with each other. It may be beneficial to perform balance and cognitive function tests earlier even at the beginning of the treatment period of COPD, and strategies should be planned to prevent the progression of functional losses.

PMID:35081270 | DOI:10.1111/crj.13469

Drug Alcohol Rev. 2022 Jan 26. doi: 10.1111/dar.13428. Online ahead of print.

ABSTRACT

INTRODUCTION: Recent trends in Australian national survey data show an increase in alcohol use among middle-aged people, amidst declines in alcohol use among other population groups. There is limited research, however, on middle-aged women’s alcohol use. This study aimed to examine patterns in alcohol use among Australian women aged 40-65 and the associated sociodemographic and contextual factors.

METHODS: Cross-sectional data from six waves of the National Drug Strategy Household Survey (2001-2019). We estimated the prevalence of long-term risky drinking (>2 Australian standard drinks per day) and risky-single occasion drinking (>5 Australian standard drinks on one occasion) among middle-aged women. Logistic regression models were estimated using 2019 data to examine demographic characteristics and contextual factors associated with alcohol use.

RESULTS: Since 2001, there has been a statistically significant increase in long-term risky drinking and risky-single occasion drinking amongst middle-aged women in Australia. Educational attainment, marital status and employment status were negatively associated with risky drinking, whereas rurality, age and location of use were positively associated with risky drinking. Beverage type was both positively and negatively associated with risky drinking.

DISCUSSION AND CONCLUSIONS: Given the significant increase in alcohol use amongst middle-aged women in Australia, prevention efforts are needed for this group, which may focus in particular on home drinking and the impact of rurality on alcohol use.

PMID:35081266 | DOI:10.1111/dar.13428