Tag: nevin manimala

Prim Care Companion CNS Disord. 2023 Feb 14;25(1):22m03267. doi: 10.4088/PCC.22m03267.

ABSTRACT

Objective: Improvement of cognitive function in patients with major depressive disorder (MDD) is an important treatment outcome. REL-1017 (esmethadone HCl) is a novel N-methyl-d-aspartate receptor (NMDAR) channel blocker and a potentially rapidly acting antidepressant. The objective of this study was to define the effects of REL-1017 on subjective cognitive measures in patients with MDD.

Methods: Post hoc analysis was conducted of subjective cognitive measures from the Montgomery-Asberg Depression Rating Scale (MADRS) and the Symptoms of Depression Questionnaire (SDQ) from a randomized, double-blind, placebo-controlled, Phase 2a study. The study, designed to assess the safety, tolerability, and efficacy of 2 dosages (25 mg and 50 mg) of REL-1017 as an adjunctive treatment in patients with MDD unresponsive to standard antidepressants, included 62 patients. We analyzed subjective cognitive measures derived from the MADRS and SDQ scales at baseline and up to day 14, 7 days after the last dose of study drug. We developed 2 composite indexes that included subjective cognitive measures selected from the MADRS and SDQ.

Results: The subanalysis of single measures and the 2 composite indexes derived from the MADRS and SDQ measures showed clinically meaningful and statistically significant improvements in cognitive function (P < .05).

Conclusions: In a Phase 2a clinical trial, REL-1017 improved subjective measures of cognitive impairment, in addition to improving total MADRS and SDQ scores. These results need to be confirmed in larger and longer studies in MDD that include objective measures of cognitive function. Phase 3 studies of REL-1017 for MDD are currently underway.

Clinical Trials Registration: ClinicalTrials.gov identifier: NCT03051256.

PMID:36821775 | DOI:10.4088/PCC.22m03267

Genome Biol Evol. 2023 Feb 23:evad032. doi: 10.1093/gbe/evad032. Online ahead of print.

ABSTRACT

The identification of genomic regions and genes that have evolved under natural selection is a fundamental objective in the field of evolutionary genetics. While various approaches have been established for the detection of targets of positive selection, methods for identifying targets of balancing selection, a form of natural selection that preserves genetic and phenotypic diversity within populations, have yet to be fully developed. Despite this, balancing selection is increasingly acknowledged as a significant driver of diversity within populations, and the identification of its signatures in genomes is essential for understanding its role in evolution. In recent years, a plethora of sophisticated methods have been developed for the detection of patterns of linked variation produced by balancing selection, such as high levels of polymorphism, altered allele frequency distributions, and polymorphism sharing across divergent populations. In this review, we provide a comprehensive overview of classical and contemporary methods, offer guidance on the choice of appropriate methods, and discuss the importance of avoiding artifacts and of considering alternative evolutionary processes. The increasing availability of genome-scale datasets holds the potential to assist in the identification of new targets and the quantification of the prevalence of balancing selection, thus enhancing our understanding of its role in natural populations.

PMID:36821771 | DOI:10.1093/gbe/evad032

Prim Care Companion CNS Disord. 2023 Feb 21;25(1):22r03304. doi: 10.4088/PCC.22r03304.

ABSTRACT

Objective: To better understand Takotsubo cardiomyopathy, a rare but life-threatening complication of acute substance withdrawal.

Data Sources: A PubMed search was conducted to identify relevant case reports through 2021 using the medical subject headings alcohol withdrawal, opioid withdrawal, benzodiazepine withdrawal OR withdrawal AND Takotsubo OR stress cardiomyopathy.

Study Selection: Case reports were included in the review if there was a diagnosis of Takotsubo cardiomyopathy in the setting of withdrawal from substances of abuse. Case reports were excluded if patients were withdrawing from other substances, actively intoxicated, or had myocardial ischemia.

Data Extraction and Synthesis: Data were manually abstracted for the variables of interest, including demographics, symptoms, medical evaluation, and treatment. Descriptive statistics of the demographics, symptoms, medical evaluation, and treatment of Takotsubo cardiomyopathy were analyzed.

Results: The mean (SD) age of patients experiencing withdrawal-associated Takotsubo cardiomyopathy was 50.8 years (15.2), and 64% of patients were female. The most common signs and symptoms were tachycardia (60%), changes in blood pressure (48%), altered mental status (48%), dyspnea (32%), nausea or vomiting (28%), and chest pain (28%). All patients with a reported electrocardiogram (92%) demonstrated ECG abnormalities; 76% had an elevated troponin level, and 24% had an elevated CK-MB level. Medications that could treat withdrawal and α₂-agonists were utilized for 60% and 12% of patients, respectively. Ventilator support, cardiopulmonary resuscitation, and intra-aortic balloon pump were needed for 24%, 8%, and 8%, respectively, of patients with withdrawal-associated Takotsubo cardiomyopathy.

Conclusions: Withdrawal-associated Takotsubo cardiomyopathy is a rare but potentially life-threatening complication of substance withdrawal. Clinicians should maintain a high degree of clinical suspicion for withdrawal-associated Takotsubo in patients with a history of substance use disorders or physical dependence on benzodiazepines or opioids, as the clinical presentation may be atypical.

PMID:36821769 | DOI:10.4088/PCC.22r03304

Occup Med (Lond). 2023 Feb 23:kqad015. doi: 10.1093/occmed/kqad015. Online ahead of print.

ABSTRACT

BACKGROUND: Current evidence is lacking to justify more stringent screening for obstructive sleep apnoea (OSA) in the rail industry. Population-based studies indicate a complex association between body mass index, age, apnoea-hypopnoea index and vehicle crash risk.

AIMS: To study the association between OSA severity and the occurrence of safety incidents in safety-critical rail workers with a confirmed diagnosis of OSA, and to identify if OSA treatment is associated with the occurrence of fewer safety incidents.

METHODS: A retrospective medical file audit was conducted on railway workers attending health assessments between 2016 and 2018, who met the criteria to be referred for sleep studies. The association between OSA severity, treatment and the number of incidents in the 3 years before their health assessment appointment was explored using a Poisson log-linear regression.

RESULTS: A substantial proportion (44%, 274/630) of railway workers with confirmed OSA had at least one incident in the 3 years prior to appointment. The odds of an incident were significantly reduced in those with moderate OSA compared with severe OSA (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.64-0.98), but not those with mild OSA (OR 0.97, 95% CI 0.76-1.24). There was a statistically significant relationship between combined OSA severity and treatment status, where the likelihood of an incident increased in those with severe untreated OSA compared with those receiving treatment (OR 1.75, 95% CI 1.16-2.64).

CONCLUSIONS: Our results suggest that more stringent screening to identify severe OSA early, and close surveillance of treatment of those with severe OSA, should be considered.

PMID:36821744 | DOI:10.1093/occmed/kqad015

MSMR. 2022 Dec 31;29(12):2-10.

ABSTRACT

The crew of USS Kidd experienced a COVID-19 outbreak identified in April 2020. This is the earliest documented COVID-19 study with RT-PCR, serology, and pre-exposure test data on the entirety of the exposed population (n=333). Case definitions included 121 confirmed (36.3% of crewmembers) and 18 probable (5.4% of crewmembers) based on laboratory diagnostic test results. At the time of testing positive, 62 (44.6%) cases reported no symptoms. Hispanic ethnicity (AOR: 2.71, CI: 1.40-5.25) and non-smoker status (AOR: 2.28, CI: 1.26-4.12) were identified as statistically significant risk factors. This study highlights the value of rapid, onboard diagnostic testing to quickly identify an outbreak and enumerate cases, as well as the serological testing to flag potential cases missed with standard viral case identification methodologies.

PMID:36821705

Surg Laparosc Endosc Percutan Tech. 2023 Feb 24. doi: 10.1097/SLE.0000000000001157. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study is to compare short-term and midterm outcomes between patients with acute pancreatitis (AP) treated with minimally invasive surgery (MIS) and patients treated with open necrosectomy (ON).

MATERIALS AND METHODS: We compared data of all patients who had undergone MIS for AP with a similar group of patients with ON patients between January 2012 and June 2021 using a case-matched methodology based on AP severity and patient characteristics. Inhospital and midterm follow-up variables, including quality-of-life assessment, were evaluated.

RESULTS: Starting from a whole series of 79 patients with moderate to critical AP admitted to our referral center, the final study sample consisted of 24 patients (12 MIS and 12 ON). Postoperative (18.7±10.9 vs. 30.3±21.7 d; P=0.05) and overall hospitalization (56.3±17.4 vs. 76.9±39.4 d; P=0.05) were lower in the MIS group. Moreover, the Short-Form 36 scores in the ON group were statistically significantly lower in role limitations because of emotional problems (P=0.002) and health changes (P=0.03) at 3 and 6 months and because of emotional problems (P=0.05), emotional well-being (P=0.02), and general health (P=0.007) at 1 year.

CONCLUSIONS: MIS for the surgical management of moderate to critical AP seems to be a good option, as it could provide more chances for a better midterm quality of life compared with ON. Further studies are needed to confirm our findings.

PMID:36821700 | DOI:10.1097/SLE.0000000000001157

Surg Laparosc Endosc Percutan Tech. 2023 Feb 20. doi: 10.1097/SLE.0000000000001153. Online ahead of print.

ABSTRACT

BACKGROUND: Thermal ablation is an accepted treatment modality for small and central liver tumors. In extensive colorectal liver metastatic disease (CRLM), hepatectomy can be combined with ablation, resulting in a parenchymal-sparing strategy. This may increase salvageability rates in case of recurrence.

METHODS: All patients with advanced CRLM that underwent combined ablation and resection between April 2012 and April 2021, were retrospectively analyzed from a prospectively maintained database. Primary endpoints include postoperative 30-day morbidity and ablation-site recurrence (ASR). The surgical approaches were compared. Ablated lesions were screened for ASR on postoperative follow-up imaging.

RESULTS: Of 54 patients that underwent combined ablation and resection, 32 (59.3%) were performed through a minimally invasive approach. Eleven (20.4%) were minor resections, 32 (59.3%) were technically major and 11 (20.4%) were anatomically major resections. Twelve complications occurred (22.2%), among which 2 (3.8%) major complications (Clavien-Dindo ≥IIIa). Ninety-day mortality rate was 1.9%. Out of 82 ablated lesions, 6 ASRs (11.1%) occurred. Median blood loss was significantly lower in the minimally invasive group, compared with open [90 mL (32.5 to 200) vs. 200 mL (100 to 400), P=0.005]. Pringle maneuver was significantly performed less in the minimally invasive group [8 (25.0%) vs. 16 (72.7%), P=0.001], but took more time [36.1 min (±15.6) vs. 21.6 (±9.9); P=0.011]. Short-term (1 y) overall and disease-free survival were respectively 81.4% and 50.0%.

CONCLUSION: Combining microwave ablation and liver resection is a feasible and safe parenchymal-sparing technique, through both minimally invasive and open approach for treating extended CRLM disease. It has a low ablation-related complication rate and acceptable ablation-site recurrence rate.

PMID:36821654 | DOI:10.1097/SLE.0000000000001153

Surg Laparosc Endosc Percutan Tech. 2023 Feb 20. doi: 10.1097/SLE.0000000000001151. Online ahead of print.

ABSTRACT

BACKGROUND: Laparoscopic distal pancreatectomy (L-DP) is the standard procedure for treating left-sided pancreatic tumors. Stapler closure of the pancreas is the preferred method for L-DP; however, postoperative pancreatic fistula (POPF) remains a challenging problem. The present study aimed to compare the surgical outcomes of staple closure using a reinforcing stapler (RS) and transection using an ultrasonic dissector followed by hand-sewn (HS) closure in a fish-mouth manner in pure L-DP and to determine independent perioperative risk factors for clinically relevant postoperative pancreatic fistula (CR-POPF).

PATIENTS AND METHODS: Among the 85 patients who underwent pure L-DP between February 2011 and August 2021, 80 of whom the pancreatic stump was closed with RS (n = 59) or HS (n = 21) were retrospectively investigated. Associations between potential risk factors and POPF were assessed using univariate analysis. The factors, of which the P value was determined to be <0.1 by univariate analysis, were entered into a multivariate regression analysis to ascertain independent predictive factors.

RESULTS: The surgery time and estimated blood loss were not significantly different between the two groups. Overall, 13 patients (16.3%) developed CR-POPF (B = 12 and C = 1). The rate of CR-POPF was lower in RS than in HS; however, the difference was not statistically significant (RS vs HS: 11.9% vs 28.9%, P = 0.092). Consistent with the results for CR-POPF, the rate of Clavien-Dindo IIIa or more postoperative complications and the length of hospital stay were also not significantly different between the two groups (RS vs HS: 10.2, 12% vs 14.3%, 14 d). In the univariate analysis of risk factors for CR-POPF, the pancreatic thickness at the transection site, procedure for stump closure, and estimated blood loss were associated with a significantly higher rate of CR-POPF. The multivariate analysis revealed that the pancreatic thickness at the transection site (cutoff: 12 mm) was the only independent risk factor for CR-POPF (odds ratio: 6.5l, 95% CI: 1.4-30.4, P = 0.018). The rate of CR-POPF was much lower in RS than in HS for pancreatic thickness <12 mm (RS vs HS: 4.1% vs 28.6%), whereas that was rather higher in RS than in HS for pancreatic thickness ≥12 mm (RS vs HS: 50% vs 28.6%).

CONCLUSIONS: RS closure was superior to HS closure for pancreatic thickness <12 mm and for prevention of CR-POPF after pure L-DP. It is necessary to seek more reliable procedures for pancreatic stump closure in patients with a pancreatic thickness of ≥12 mm.

PMID:36821651 | DOI:10.1097/SLE.0000000000001151

PLoS Genet. 2023 Feb 23;19(2):e1010596. doi: 10.1371/journal.pgen.1010596. eCollection 2023 Feb.

ABSTRACT

Genetic studies of disease progression can be used to identify factors that may influence survival or prognosis, which may differ from factors that influence on disease susceptibility. Studies of disease progression feed directly into therapeutics for disease, whereas studies of incidence inform prevention strategies. However, studies of disease progression are known to be affected by collider (also known as “index event”) bias since the disease progression phenotype can only be observed for individuals who have the disease. This applies equally to observational and genetic studies, including genome-wide association studies and Mendelian randomisation (MR) analyses. In this paper, our aim is to review several statistical methods that can be used to detect and adjust for index event bias in studies of disease progression, and how they apply to genetic and MR studies using both individual- and summary-level data. Methods to detect the presence of index event bias include the use of negative controls, a comparison of associations between risk factors for incidence in individuals with and without the disease, and an inspection of Miami plots. Methods to adjust for the bias include inverse probability weighting (with individual-level data), or Slope-Hunter and Dudbridge et al.’s index event bias adjustment (when only summary-level data are available). We also outline two approaches for sensitivity analysis. We then illustrate how three methods to minimise bias can be used in practice with two applied examples. Our first example investigates the effects of blood lipid traits on mortality from coronary heart disease, while our second example investigates genetic associations with breast cancer mortality.

PMID:36821633 | DOI:10.1371/journal.pgen.1010596

PLoS One. 2023 Feb 23;18(2):e0282138. doi: 10.1371/journal.pone.0282138. eCollection 2023.

ABSTRACT

AIMS: This study aimed to determine the impact of correlates on tobacco control/smoke-free status of homes and workplace among Indian people. To assess the magnitude of the problem, the relationship between smoke-free status and secondhand smoke (SHS) exposure was also explored.

METHODS: Data was extracted from the Global Adult Tobacco Survey Data (GATS)-2017. It was a household survey that included people aged 15 years or older and covered all 30 states and 2 Union Territories (UTs) of India. A logistic regression model was used to determine the correlates of smoke-free status of homes and workplaces. Additionally, the Pearson correlation was used to explore the relationship between smoke-free status and the proportion of participants exposed to SHS both at homes and in the workplaces.

RESULTS: The overall prevalence of smoke-free status in the home and workplace was 62.8% and 51.7%, respectively. Results of multivariate analysis (Logistic regression) illustrated that indicators like tobacco smoking status, place of residence, region, education, occupation, wealth quintile, and knowledge status about children’s illness were significantly associated with the respondent’s intention to live in a completely smoke-free environment both at home and in the workplace in India. This study revealed that SHS exposure was significantly negatively associated with a smoke-free status.

CONCLUSION: This study will help the policymakers to promote efficient policies for improving smoke-free status and to ensure a better environment both at home and in the workplace in India.

PMID:36821629 | DOI:10.1371/journal.pone.0282138