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Nevin Manimala Statistics

SARS-CoV-2 Effects on Psychophysical Olfactory Scores: Prospective Study With Evaluation Before and 60-Days After Infection

Otolaryngol Head Neck Surg. 2023 Feb 23. doi: 10.1002/ohn.166. Online ahead of print.

ABSTRACT

The aim of this study was to prospectively evaluate the olfactory function in a series of individuals infected with SARS-CoV-2 and who had undergone psychophysical olfactory assessment prior to infection. Individuals unexposed to SARS-CoV-2 infection underwent a psychophysical evaluation of smell with the Sniffin’ Sticks test. The subjects were followed prospectively and included in the study if they developed SARS-CoV-2 infection with a second test 60 days after recovery. At the 60-day follow-up of the 41 included subjects, 2 (4.9%) self-reported persistent olfactory dysfunction (OD). The differences between TDI scores before and after infection were statistically significant (37 [interquartile range (IQR), 34.25-39.25] vs 34.75 [IQR, 32.25-38]; p = .021). Analyzing the individual olfactory domains, the differences were significant for threshold (T) (9.75 [IQR, 9-11.25] vs 8.25 [IQR, 7.25-10.25]; p = .009) but not for odor discrimination (D) (p = .443) and identification (I) (p = .159). SARS-CoV-2 causes a significant reduction in the olfactory function, in particular affecting the olfactory threshold, even in subjects who do not self-report an OD.

PMID:36821798 | DOI:10.1002/ohn.166

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Evaluation of polygenic risk scores to differentiate between type 1 and type 2 diabetes

Genet Epidemiol. 2023 Feb 23. doi: 10.1002/gepi.22521. Online ahead of print.

ABSTRACT

Polygenic risk scores (PRS) quantify the genetic liability to disease and are calculated using an individual’s genotype profile and disease-specific genome-wide association study (GWAS) summary statistics. Type 1 (T1D) and type 2 (T2D) diabetes both are determined in part by genetic loci. Correctly differentiating between types of diabetes is crucial for accurate diagnosis and treatment. PRS have the potential to address possible misclassification of T1D and T2D. Here we evaluated PRS models for T1D and T2D in European genetic ancestry participants from the UK Biobank (UKB) and then in the Michigan Genomics Initiative (MGI). Specifically, we investigated the utility of T1D and T2D PRS to discriminate between T1D, T2D, and controls in unrelated UKB individuals of European ancestry. We derived PRS models using external non-UKB GWAS. The T1D PRS model with the best discrimination between T1D cases and controls (area under the receiver operator curve [AUC] = 0.805) also yielded the best discrimination of T1D from T2D cases in the UKB (AUC = 0.792) and separation in MGI (AUC = 0.686). In contrast, the best T2D model did not discriminate between T1D and T2D cases (AUC = 0.527). Our analysis suggests that a T1D PRS model based on independent single nucleotide polymorphisms may help differentiate between T1D, T2D, and controls in individuals of European genetic ancestry.

PMID:36821788 | DOI:10.1002/gepi.22521

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Subanalysis of Subjective Cognitive Measures From a Phase 2, Double-Blind, Randomized Trial of REL-1017 in Patients With Major Depressive Disorder

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

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Inferring balancing selection from genome-scale data

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

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Substance Withdrawal-Associated Takotsubo Cardiomyopathy: A Review of the Literature

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

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Safety incidents and obstructive sleep apnoea in railway workers

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

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Seroepidemiologic Investigation of a COVID-19 Outbreak Aboard a U.S. Navy Ship

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

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Minimally Invasive Surgery for the Treatment of Moderate to Critical Acute Pancreatitis: A Case-matched Comparison With the Traditional Open Approach Over 10 years

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

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Combined Ablation and Resection for Colorectal Liver Metastases in the Minimally Invasive Surgical Era

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

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Efficacy of Reinforced Stapler Versus Hand-sewn Closure of the Pancreatic Stump During Pure Laparoscopic Distal Pancreatectomy to Reduce Pancreatic Fistula

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