Nevin Manimala

Neuro Oncol. 2023 Oct 4;25(Supplement_4):iv1-iv99. doi: 10.1093/neuonc/noad149.

ABSTRACT

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous CBTRUS reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 24.83 per 100,000 population (malignant AAAIR=6.94 and non-malignant AAAIR=17.88). This overall rate was higher in females compared to males (27.85 versus 21.62 per 100,000) and non-Hispanic persons compared to Hispanic persons (25.24 versus 22.61 per 100,000). Gliomas accounted for 26.3% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (14.2% of all tumors and 50.9% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (40.8% of all tumors and 56.2% of all non-malignant tumors). Glioblastomas were more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.13 per 100,000 population. There were 86,030 deaths attributed to malignant brain and other CNS tumors between 2016 and 2020. This represents an average annual mortality rate of 4.42 per 100,000 population and an average of 17,206 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 35.7%, for a non-malignant brain and other CNS tumor the five-year relative survival rate was 91.8%.

PMID:37793125 | DOI:10.1093/neuonc/noad149

Epidemiology. 2023 Oct 2. doi: 10.1097/EDE.0000000000001680. Online ahead of print.

ABSTRACT

BACKGROUND: To meet regulatory approval, interventions must demonstrate efficacy against a primary outcome in randomized clinical trials. However, when there are multiple clinically relevant outcomes, selecting a single primary outcome is challenging. Incorporating data from multiple outcomes may increase statistical power in clinical trials. We examined methods for analyzing data on multiple endpoints, inspired by real-world trials of interventions against respiratory syncytial virus (RSV).

METHOD: We developed a novel permutation test representing a weighted average of individual outcome test statistics (wavP) to evaluate intervention efficacy in a multiple-endpoint analysis. We compared the power and type I error rate of this approach to the Bonferroni correction (bonfT) and the minP permutation test. We evaluated the different approaches using simulated data from three hypothetical trials varying the intervention efficacy, correlation, and incidence of the outcomes, as well as data from a real-world RSV clinical trial.

RESULTS: When the vaccine efficacy against different outcomes was similar, wavP yielded higher power than bonfT and minP; in some scenarios the improvement in power was substantial. In settings where vaccine efficacy was notably larger against one endpoint compared to the others, all three methods had similar power. We developed an R package, PERMEATE, to guide selection of the most appropriate method for analyzing multiple endpoints in clinical trials.

CONCLUSIONS: Analyzing multiple endpoints using a weighted permutation method can increase power while controlling the type I error rate compared to established methods under conditions mirroring real-world RSV clinical trials.

PMID:37793120 | DOI:10.1097/EDE.0000000000001680

Med Phys. 2023 Oct 4. doi: 10.1002/mp.16774. Online ahead of print.

ABSTRACT

BACKGROUND: Pulsed wave Doppler ultrasound is a useful modality for assessing vascular health as it quantifies blood flow characteristics. To facilitate accurate diagnosis, accuracy and consistency of this modality should be assessed through Doppler quality assurance (QA).

PURPOSE: The purpose of this study was to characterize the accuracy, reproducibility, and inter-scanner variability of ultrasound flow velocity measurements via a flow phantom, with a focus on the effect of systematic acquisition parameters on measured flow velocity accuracy.

METHODS: Using a manufacturer-calibrated flow phantom, pulsed wave measurements were acquired on five clinical systems (iU22, Philips) with three models of transducers, including both linear and curvilinear models. The peak and mean flow velocities were estimated by vendor-supplied spectral analysis tools. To investigate intra- and inter-scanner variability, measurements were repeated using each scanner-transducer pair under a standardized set of conditions. Inter-scanner variability was assessed using ANOVA. Flow velocity accuracy was investigated by mean absolute percentage error. The impacts of receive gain, measurement depth, and beam steering on measured flow velocity accuracy were examined by varying each parameter over its available range and comparing to the ground truth flow velocity.

RESULTS: Inter-scanner variability was statistically significant for peak flow measurements made using both linear and curvilinear transducers, though absolute differences in measured velocity were small. Inter-scanner variability was not statistically significant for mean flow velocity. Receive gain, measurement depth, and beam steering were all found to impact the accuracy of measured flow characteristics for linear transducers. Accuracy of the flow measurements made with the curvilinear transducer demonstrated high consistency to changes in receive gain at a constant depth, though were impacted by increasing the measurement depth.

CONCLUSIONS: Carefully and consistently selected acquisition and set-up parameters are essential in order to establish a reliable and meaningful QA program.

PMID:37793117 | DOI:10.1002/mp.16774

Epidemiology. 2023 Oct 2. doi: 10.1097/EDE.0000000000001683. Online ahead of print.

ABSTRACT

BACKGROUND: To our knowledge, no studies have explicitly studied the role of hypertensive disorders of pregnancy (HDP) in racial disparities in severe maternal morbidity (SMM).

METHODS: Using causal mediation models, we estimated the proportion of the non-Hispanic Black-White racial disparity in risk of SMM that is explained through the pathway of HDP. We linked 2006-2019 Georgia hospital discharge records with vital statistics birth and fetal death records for non-Hispanic Black and non-Hispanic White birthing persons. We used G-estimation of a structural nested mean model to decompose the absolute racial disparity in incidence of SMM into pathways operating through HDP.

RESULTS: Non-Hispanic Black birthing people experienced an excess 56 SMM events (95% CI: 52, 59) per 10,000 delivery hospitalizations compared to non-Hispanic White birthing people. If counterfactual disparity measure estimation assumptions hold, the estimated absolute disparity remaining after blocking the causal pathways through HDP was 41 SMM events per 10,000 deliveries (95% CI: 38, 44), suggesting that 26% (95% CI: 12, 40) of the absolute racial disparity would be eliminated if there was no contribution of HDP to SMM risk.

CONCLUSIONS: Our results are consistent with the hypothesis that intervening to prevent HDP is an important (yet incomplete) pathway for reducing the excess risk among NH Black pregnancies compared to NH White pregnancies.

PMID:37793115 | DOI:10.1097/EDE.0000000000001683

JCO Oncol Pract. 2023 Oct 4:OP2300147. doi: 10.1200/OP.23.00147. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the enrollment success rate of cancer clinical trials conducted in 2008-2019 and various factors lowering the enrollment success rate.

METHODS: This is a cross-sectional study with clinical trial information from the largest registration database ClinicalTrials.gov. Enrollment success rate was defined as actual enrollment greater or equal to 85% of the estimated enrollment goal. The association between trial characteristics and enrollment success was evaluated using the multivariable logistic regression.

RESULTS: A total of 4,004 trials in breast, lung, and colorectal cancers were included. The overall enrollment success rate was 49.1%. Compared with 2008-2010 (51.5%) and 2011-2013 (52.1%), the enrollment success rate is lower in 2014-2016 (46.5%) and 2017-2019 (36.4%). Regression analyses found trial activation year, phase I, phase I/phase II, and phase II (v phase III), sponsor agency of government (v industry), not requiring healthy volunteers, and estimated enrollment of 50-100, 100-200, 200, and >500 (v 0-50) were associated with a lower enrollment success rate (P < .05). However, trials with placebo comparator, ≥5 locations (v 1 location), and a higher number of secondary end points (eg, ≥5 v 0) were associated with a higher enrollment success rate (P < .05). The AUC for prediction of the final logistic regression models for all trials and specific trial groups ranged from 0.69 to 0.76.

CONCLUSION: This large-scale study supports a lower enrollment success rate over years in cancer clinical trials. Identified factors for enrollment success can be used to develop and improve recruitment strategies for future cancer trials.

PMID:37793091 | DOI:10.1200/OP.23.00147

Int J Dent Hyg. 2023 Oct 4. doi: 10.1111/idh.12771. Online ahead of print.

ABSTRACT

INTRODUCTION: The world’s population is in a demographic transition with a rising ageing population. Tooth loss is frequent among older people resulting in the replacement of natural teeth using complete or partial dentures. YouTube™ is the second most popular website in the world and is being increasingly used to access health care information. The aim of this study is to evaluate the usefulness and reliability of the information in YouTube™ videos regarding denture care.

METHODS: The YouTube™ website was used to systematically search for videos using the keyword ‘denture care’. Videos meeting the eligibility criteria were assessed separately by two independent researchers. The usefulness of the videos was assessed using the Global Quality Assessment Scale and a customized usefulness scoring scheme. Based on these scores, the usefulness of the videos was categorized as low, medium and high. A modified DISCERN tool (mDISCERN) was used for assessing reliability with scores ranging from 0 to 5. Other video characteristics like source/ownership of the videos, duration, views, likes, dislikes, number of days posted, like ratio, view ratio, interaction index and Video Power Index were also obtained. Statistical analysis was carried out using the Kruskal-Wallis test, Spearman correlation test and multiple linear regression analysis.

RESULTS: A total of 120 videos were included. Based on the usefulness score, the usefulness of 65.8% of videos were classified as low, 32.5% were medium and 1.6% had high usefulness. The mDISCERN score for 74.2% of videos was 2 or below 2 indicating that the majority of videos had low reliability. Video characteristics did not differ significantly according to the usefulness of videos. Videos uploaded by dentists or dental hygienists had significantly higher usefulness scores (p < 0.001) in comparison to videos uploaded by other sources. However, reliability scores did not differ based on the sources of the videos. Video reliability was found to have a significant (B = 2.08, p < 0.001) positive association with video usefulness.

CONCLUSION: YouTube™ cannot be recommended as the only source of information for denture care as most videos received low usefulness and reliability ratings in our study. Dentists and dental health professionals could take an active part in enhancing denture care-related content on YouTube™ and enable patients to have adequate and reliable knowledge of denture hygiene practices.

PMID:37793081 | DOI:10.1111/idh.12771

Inflamm Bowel Dis. 2023 Oct 4:izad227. doi: 10.1093/ibd/izad227. Online ahead of print.

ABSTRACT

BACKGROUND: Very few risk factors for postoperative recurrence (POR) of Crohn’s Disease (CD) after ileocecal resection have been identified. The aim of the present study was to verify the association between an a priori defined list of intraoperative macroscopic findings and POR.

METHODS: This was a prospective observational study including patients undergoing primary ileocecal resection for CD. Four intraoperative factors were independently evaluated by 2 surgeons: length of resected ileum, mesentery thickness, presence of areas of serosal fat infiltration, or abnormal serosal vasodilation on normal bowel proximal to the resected bowel. The primary end point was early endoscopic POR at month 6 and defined as modified Rutgeerts score ≥i2b. Secondary end points were clinical and surgical recurrence.

RESULTS: Between September 2020 and November 2022, 83 consecutive patients were included. Early endoscopic recurrence occurred in 45 of 76 patients (59.2%). Clinical and biochemical recurrence occurred in 17.3% (95% confidence interval, [CI], 10.4%-28.0%) and 14.6% of the patients after 12 months. The risk of developing endoscopic and clinical recurrence was 1.127 (95% CI, 0.448;2.834, P = .799) and 0.896 (95% CI, 0.324-2.478, P = .832) when serosal fat infiltration was observed, and 1.388 (95% CI, 0.554-3.476, P = .484), and 1.153 (95% CI, 0.417;3.187, P = .783) when abnormal serosal vasodilation was observed. Similarly, length of the resected bowel and mesentery thickness showed no association with POR. A subgroup analysis on patients who received no postoperative medical prophylaxis did not identify any risk factor for endoscopic POR.

CONCLUSIONS: The macroscopic appearance of the bowel and associated mesentery during surgery does not seem to be predictive of POR after ileocecal resection for CD.

PMID:37793044 | DOI:10.1093/ibd/izad227

Psychiatriki. 2023 Sep 29. doi: 10.22365/jpsych.2023.023. Online ahead of print.

ABSTRACT

The COVID-19 pandemic has caused a mental health crisis. The purpose of this study was to estimate the prevalence of depression in medical students in Greece during a nationwide lockdown. The secondary aims were to assess the association of depression with socio-demographic factors and students’ attitudes regarding the quality of their studies. The data was gathered anonymously through a self-administered online questionnaire between January 11 and 27, 2021. The CES-D scale was used to measure depression rates. Multiple logistic regression was used to identify factors independently associated with depression. Analyses were conducted using Stata version 16.0 and the IBM® SPSS® software. In total, 978 sixth- and fifth-year medical students participated; their mean age was 23.2 years and 65.6% were females. The prevalence of clinical depression was 21.3% (95% CI: 18.7%, 24.0%), whereas 17.9% (95% CI: 15.5%, 20.4%) experienced severe distress. Depression was more prevalent in females (25.4% vs 13.1% in males, p<0.001). Approximately half (53.4%) of the participants reported a change in plans regarding their medical career due to the pandemic and 16.9% expressed a decreased willingness to practice medicine. Factors independently associated with depression were female gender, living alone or with housemates at high risk for COVID-19, being anxious about becoming infected with SARS-CoV-2, studying in one of the three largest medical schools, negatively evaluating the adjustment of the teaching personnel to online teaching and the university’s response to the pandemic. The findings of this study report depression in one out of five medical students during the COVID-19 pandemic, highlighting the need to protect the most vulnerable medical students during a pandemic. Medical students must be able to seek professional mental health services, even in the era of a pandemic. Universities should increase accessibility to support services and provide a student-centered approach in their strategies, as the pandemic has placed a spotlight on an existing phenomenon.

PMID:37793037 | DOI:10.22365/jpsych.2023.023

Psychiatriki. 2023 Sep 29. doi: 10.22365/jpsych.2023.022. Online ahead of print.

ABSTRACT

Despite its significant decline in the general population, smoking remains endemic and highly prevalent among people with mental disorders. The impact of smoking-attributable morbidity on life expectancy is significant since, in comparison to the general population, people with severe mental disorders have a 15-20-year reduction in life expectancy. A cross-sectional study was conducted among 1015 people with mental disorders through personal interviews. The questionnaire was designed to examine these patients’ knowledge, perceptions, and attitudes towards smoking. Individuals were recruited from the mental health residential community services, the outpatient department, and the inpatient facilities of the Psychiatric Hospital of Attica. Statistical analysis was performed using SPSS 26.0. In the sample analyzed, the current-smoking prevalence stood at 68.4% (n=643), while 12.3% reported being former smokers. A staggering 86.3% smoked their first cigarette within 30 minutes of waking up, indicating a high level of dependence. Most of the former smokers (83.6%) reported that their main reason for quitting smoking was to improve their health, and the overwhelming majority (97.4%) had done so using no smoking cessation aid. Although slightly over half of the participants (53.7%) believed that health professionals adequately inform smokers about the harmful health effects of tobacco products, the information provided by health professionals on smoking cessation programs and tobacco harm reduction alternatives was considered sufficient by a mere 11.2%. Multiple logistic regression analysis demonstrated that outpatients tended to have a greater likelihood of being current smokers as compared to inpatients (OR=1.45), while users of mental health residential community services showed a significantly lower likelihood of being current smokers in comparison to inpatients (OR=0.49). Additionally, it was found that women had a lower likelihood of being current smokers compared to men (OR=0.51), while divorced/ widowed participants had a greater likelihood of being current smokers compared to single ones (OR=1.93). Finally, multiple regression analysis indicated that participants with psychotic disorders displayed a 2.39 times greater likelihood of being current smokers compared to those with mood disorders (OR=2.39). Understanding the knowledge, beliefs, and attitudes of people with mental disorders towards tobacco is an essential first step to confronting this neglected epidemic.

PMID:37793036 | DOI:10.22365/jpsych.2023.022

J Chem Theory Comput. 2023 Oct 4. doi: 10.1021/acs.jctc.3c00571. Online ahead of print.

ABSTRACT

Most electrochemical reactions should be studied under a grand canonical ensemble condition with a constant potential and/or a constant pH value. Free energy profiles provide key insights into understanding the reaction mechanisms. However, many molecular dynamics (MD)-based theoretical studies for electrochemical reactions did not employ an exact grand canonical ensemble sampling scheme for the free energy calculations, partially due to the issues of discontinuous trajectories induced by the particle-number variations during MD simulations. An alternative statistical sampling approach, the Monte Carlo (MC) method, is naturally appropriate for the open-system simulations if we focus on the thermodynamic properties. An advanced MC scheme, the hybrid Monte Carlo (HMC) method, which can efficiently sample the configurations of a system with large degrees of freedom, however, has limitations in the constrained-sampling applications. In this work, we propose an adjusted constrained HMC method to compute free energy profiles using the thermodynamic integration (TI) method. The key idea of the method for handling the constraint in TI is to integrate the reaction coordinate and sample the rest degrees of freedom by two types of MC schemes, the HMC scheme and the Metropolis algorithm with unbiased trials (M(RT)²-UB). We test the proposed method on three different systems involving two kinds of reaction coordinates, which are the distance between two particles and the difference of particles’ distances, and compare the results to those generated by the constrained M(RT)²-UB method serving as benchmarks. We show that our proposed method has the advantages of high sampling efficiency and convenience of implementation, and the accuracy is justified as well. In addition, we show in the third test system that the proposed constrained HMC method can be combined with the path integral method to consider the nuclear quantum effects, indicating a broader application scenario of the sampling method reported in this work.

PMID:37793028 | DOI:10.1021/acs.jctc.3c00571