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Nevin Manimala Statistics

Genetic correlation and gene-based pleiotropy analysis for four major neurodegenerative diseases with summary statistics

Neurobiol Aging. 2022 Dec 31:S0197-4580(22)00275-5. doi: 10.1016/j.neurobiolaging.2022.12.012. Online ahead of print.

ABSTRACT

Recent genome-wide association studies suggested shared genetic components between neurodegenerative diseases. However, pleiotropic association patterns among them remain poorly understood. We here analyzed 4 major neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), and found suggestively positive genetic correlation. We next implemented a gene-centric pleiotropy analysis with a powerful method called PLACO and detected 280 pleiotropic associations (226 unique genes) with these diseases. Functional analyses demonstrated that these genes were enriched in the pancreas, liver, heart, blood, brain, and muscle tissues; and that 42 pleiotropic genes exhibited drug-gene interactions with 341 drugs. Using Mendelian randomization, we discovered that AD and PD can increase the risk of developing ALS, and that AD and ALS can also increase the risk of developing FTD, respectively. Overall, this study provides in-depth insights into shared genetic components and causal relationship among the 4 major neurodegenerative diseases, indicating genetic overlap and causality commonly drive their co-occurrence. It also has important implications on the etiology understanding, drug development and therapeutic targets for neurodegenerative diseases.

PMID:36740554 | DOI:10.1016/j.neurobiolaging.2022.12.012

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Nevin Manimala Statistics

Efficacy and safety of Majoon Ushba oral and Marham Raal topical in tinea corporis – A randomized open-labeled active-controlled clinical trial

Explore (NY). 2023 Jan 25:S1550-8307(23)00028-9. doi: 10.1016/j.explore.2023.01.005. Online ahead of print.

ABSTRACT

OBJECTIVE: Tinea Corporis is the most frequent form of dermatophytosis reported as the commonest presentation. Majoon Ushba (MU) a polyherbal preparation in a semisolid oral dosage form and Marham Raal (MR) an ointment made up of herbal and animal drugs are used for skin disorders in Unai medicine. Considering the biologically active substances with antioxidant, antimicrobial, antifungal, anti-inflammatory, and wound-healing properties of their ingredients, this study aimed to evaluate the clinical and mycological efficacy and safety of MU and MR in tinea corporis.

METHODS: This randomized open-labeled active-controlled clinical trial was conducted on 42 patients of tinea corporis. Patients were randomly assigned via a computer-generated list to the test group (n=21) receiving oral MU (6 gm) with topical MR and the control group (n=21) topical terbinafine hydrochloride (1%) for 40 days. The severity scores of clinical symptoms; erythema, scaling, itching, margins, and size were the primary outcome and the mycological cure (negative KOH microscopy), total score, and dermatology life quality index (DLQI) were the secondary outcomes were analyzed at baseline and at 40 days.

RESULTS: A significant reduction was observed in clinical severity scores of erythema, scaling, and itching (P ≤ 0.05) in both groups except for margins, and size of the lesion (P ≥ 0.05). The mycological cure (P = .001) and the total score (P = 0.0002) and DLQI (P = 0.002) were statistically significant in both groups when analyzed from baseline to the end of the treatment within groups, however, the differences in these outcomes were statistically insignificant (P ≥ 0.05) on the inter-group comparison. All the safety parameters (clinical and laboratory) were in the normal range in both groups.

CONCLUSION: The results demonstrated that traditional and conventional treatments were equally effective and MU and MR can be prescribed as alternative or complementary treatments for tinea corporis.

PMID:36740535 | DOI:10.1016/j.explore.2023.01.005

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Nevin Manimala Statistics

Facilitating pharmacy staff’s conversations about non-medical medication switches: Development and testing of a communication training

Res Social Adm Pharm. 2023 Jan 31:S1551-7411(23)00034-7. doi: 10.1016/j.sapharm.2023.01.014. Online ahead of print.

ABSTRACT

BACKGROUND: Non-medical medication switches, a change to another medicine or medication label not motivated by medical reasons, occur frequently. Switches often lead to negative patient emotions, such as confusion and anger. Pharmacy staff’s communication, i.e. delivering the message and addressing patients’ emotions is crucial, but experienced as difficult.

OBJECTIVE: To develop and test a communication training for the pharmacy team to facilitate medication switch conversations.

METHODS: A communication training was developed based on the ‘breaking bad news model’ and ‘positive message framing’ strategies, and incorporating needs and preferences from practice. The training consisted of an e-learning with theory and reflective exercises, a half-day live training session, and an online reflection session. The Kirkpatrick training evaluation model (levels one ‘reaction’ and two ‘learning’) was used to evaluate the training. Quantitative data were analyzed using descriptive statistics and interview data was transcribed verbatim and analyzed thematically.

RESULTS: Twelve pharmacists and 27 pharmacy technicians from 15 Dutch pharmacies participated in the training. According to Kirkpatrick’s model level one, the major learning outcome was to give space to patients to express their emotions and/or concerns (e.g. more silences in the conversations). For level two, most participants valued practicing the conversations, role-playing, and receiving feedback. The majority of the participants indicated that they had sufficient tools and practice during the live training to apply the strategies in daily practice. A few participants still needed time and practice, or missed examples to apply the strategies.

CONCLUSION: The communication training based on the two strategies was well-received and participants felt well-equipped post-training. The take-away for participants was to give space to patients to express their emotions. Using these strategies and skills, pharmacy teams can tailor their medication counseling to patients’ emotions and concerns during non-medical medication switches to better support patients in proper medication use.

PMID:36740526 | DOI:10.1016/j.sapharm.2023.01.014

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Nevin Manimala Statistics

The male patient with obesity undergoing metabolic and bariatric surgery: changes in testosterone levels correlate with weight loss after one-anastomosis gastric bypass and Roux-en-Y gastric bypass

Surg Obes Relat Dis. 2022 Dec 30:S1550-7289(22)00830-9. doi: 10.1016/j.soard.2022.12.034. Online ahead of print.

ABSTRACT

BACKGROUND: Male obesity secondary hypogonadism (MOSH) is a common disease among men with obesity and can be associated with metabolic syndrome and a variety of metabolic problems ultimately leading to androgen deficiency. Metabolic and bariatric surgery is a well-established treatment option associated with significant weight loss and reduction in metabolic co-morbidities.

OBJECTIVES: To evaluate the impact of surgery on plasma levels of sexual hormones and their effect on weight loss comparing 2 surgical methods (one-anastomosis gastric bypass [OAGB] and Roux-en-Y gastric bypass [RYGB]) in male patients with obesity.

SETTING: University hospital, Austria.

METHODS: Patients undergoing OAGB and RYGB between 2012 and 2017 were analyzed retrospectively. Follow-up in this study was up to 24 months. Systemic levels of sexual hormones (luteinizing hormone [LH]), follicle stimulating hormone [FSH], total testosterone [TT], sexual hormone binding globin [SHBG], 17 beta-estradiol [17bE], androstenedione [AS]) were retrieved at each visit. A linear mixed model was used to assess the correlation between changes in testosterone levels and percent excess weight loss (%EWL).

RESULTS: In 30.8% of all patients, MOSH was present preoperatively. A significant increase of TT was observed postoperatively that led to a complete resolution of hypogonadism within the period observed. Bioavailable testosterone (bTT) and FSH levels significantly increased each month of follow-up after surgery (all P < .01). Levels of 17bE did not change significantly after surgery. The overall change of TT, comparing preoperative and 1-year postoperative TT levels (ΔTT), significantly correlated with %EWL. Changes in TT levels were not affected by the choice of surgical method.

CONCLUSIONS: Serum plasma testosterone levels rise significantly after metabolic and bariatric surgery in male patients. The change of testosterone levels seems to play a role in continued weight loss after surgery. This is true irrespective of the surgical method used.

PMID:36740523 | DOI:10.1016/j.soard.2022.12.034

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Nevin Manimala Statistics

Bayesian multivariant fine mapping using the Laplace prior

Genet Epidemiol. 2023 Feb 5. doi: 10.1002/gepi.22517. Online ahead of print.

ABSTRACT

Currently, the only effect size prior that is routinely implemented in a Bayesian fine-mapping multi-single-nucleotide polymorphism (SNP) analysis is the Gaussian prior. Here, we show how the Laplace prior can be deployed in Bayesian multi-SNP fine mapping studies. We compare the ranking performance of the posterior inclusion probability (PIP) using a Laplace prior with the ranking performance of the corresponding Gaussian prior and FINEMAP. Our results indicate that, for the simulation scenarios we consider here, the Laplace prior can lead to higher PIPs than either the Gaussian prior or FINEMAP, particularly for moderately sized fine-mapping studies. The Laplace prior also appears to have better worst-case scenario properties. We reanalyse the iCOGS case-control data from the CASP8 region on Chromosome 2. Even though this study has a total sample size of nearly 90,000 individuals, there are still some differences in the top few ranked SNPs if the Laplace prior is used rather than the Gaussian prior. R code to implement the Laplace (and Gaussian) prior is available at https://github.com/Kevin-walters/lapmapr.

PMID:36739616 | DOI:10.1002/gepi.22517

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Nevin Manimala Statistics

An integrated strategy for the geographical origin traceability of Goji berries by antioxidants characteristic fingerprint based on-line ultra performance liquid chromatography-2,2-diphenyl-1-picrylhydrazyl- photodiode array detector-MS combined with multivariate statistics analysis

J Sep Sci. 2023 Feb 5:e2200826. doi: 10.1002/jssc.202200826. Online ahead of print.

ABSTRACT

Goji berries are now becoming increasingly popular in the human diet due to their potential health benefits. Unscrupulous traders deliberately mislabel with certain origins to gain illegal profits, which seriously affected the consumers’ benefits. In this study, an on-line ultra performance liquid chromatography-2,2-diphenyl-1 -picrylhydrazyl-photodiode array detector-electrospray ionization-quadrupole time of flight mass was developed for rapid screening and identification of the antioxidants from Goji berry; then, the antioxidants characteristic fingerprint was established and explored in the origins discrimination of Goji berries from China combined with multivariate statistics analysis. As a result, twenty-eight compounds were screened from Goji berry extract, 19 of which were identified by accurate molecular and ultraviolet information according references. Principal components analysis and partial least squares discrimination analysis achieved the accurate classification from the four regions, eight compounds were selected as origin-related antioxidant markers with variable importance in projection >1 and one-way analysis of variance (P<0.05), including rutin, rutin di-hexose, P-coumaric acid tri-hexose, dicaffeoylquinic acid isomer, Quercetin-rhamno-di-hexoside, peak14, peak16, and peak27. This study provides a feasible strategy for the geographical origins discrimination of Goji berries based on antioxidant ingredients difference, and will be helpful for improving the quality control level of Goji berry. This article is protected by copyright. All rights reserved.

PMID:36739594 | DOI:10.1002/jssc.202200826

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Nevin Manimala Statistics

Shared genetics and causal relationships between migraine and thyroid function traits

Cephalalgia. 2023 Feb;43(2):3331024221139253. doi: 10.1177/03331024221139253.

ABSTRACT

BACKGROUND: Epidemiological studies have reported a comorbid relationship between migraine and thyroid dysfunction.

METHODS: We investigated the genetic relationship between migraine and thyroid function traits using genome-wide association study (GWAS) data.

RESULTS: We found a significant genetic correlation (rg) with migraine for hypothyroidism (rg = 0.0608), secondary hypothyroidism (rg = 0.195), free thyroxine (fT4) (rg = 0.0772), and hyperthyroidism (rg = -0.1046), but not thyroid stimulating hormone (TSH). Pairwise GWAS analysis revealed two shared loci with TSH and 11 shared loci with fT4. Cross-trait GWAS meta-analysis of migraine identified novel genome-wide significant loci: 17 with hypothyroidism, one with hyperthyroidism, five with secondary hypothyroidism, eight with TSH, and 15 with fT4. Of the genes at these loci, six (RERE, TGFB2, APLF, SLC9B1, SGTB, BTBD16; migraine + hypothyroidism), three (GADD45A, PFDN1, RSPH6A; migraine + TSH), and three (SSBP3, BRD3, TEF; migraine + fT4) were significant in our gene-based analysis (pFisher’s combined P-value < 2.04 × 10-6). In addition, causal analyses suggested a negative causal relationship between migraine and hyperthyroidism (p = 8.90 × 10-3) and a positive causal relationship between migraine and secondary hypothyroidism (p = 1.30 × 10-3).

CONCLUSION: These findings provide strong evidence for genetic correlation and suggest complex causal relationships between migraine and thyroid traits.

PMID:36739509 | DOI:10.1177/03331024221139253

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Nevin Manimala Statistics

Efficacy of bedside optic nerve sheath diameter measurement in differentiating provoked seizure from unprovoked seizure in the emergency department

Ann Saudi Med. 2023 Jan-Feb;43(1):42-49. doi: 10.5144/0256-4947.2023.42. Epub 2023 Feb 2.

ABSTRACT

BACKGROUND: Emergency departments (EDs) are typically the first medical contact for seizure patients, and early diagnosis and treatment is primarily the responsibility of emergency physicians.

OBJECTIVES: Demonstrate the efficacy of bedside ocular ultrasonography for optic nerve sheath diameter (ONSD) measurement in differentiating provoked seizure from unprovoked seizure in the ED.

DESIGN: Prospective observational study SETTINGS: Tertiary care hospital PATIENTS AND METHODS: Patients presenting to the ED with seizure were divided into two groups according to medical history, physical examination, laboratory results, cranial computed tomography findings and electroencephalography results. Patients with seizures that did not have a specific cause (unprovoked) were compared with patients who had seizures caused by underlying pathology (provoked). The measurement of the ONSD was taken at the bedside within 30 minutes of arrival. The study compared the ONSD values, age, sex, type of seizure, and Glasgow Coma Score between the two groups.

MAIN OUTCOME MEASURE: Efficacy of ONSD to distinguish between provoked and unprovoked seizures.

SAMPLE SIZE: 210 patients RESULTS: One hundred and fourteen (54.3%) patients were in the provoked seizure group and 96 (45.7%) were in the unprovoked seizure group. The ONSD measurements were significantly higher in the provoked seizure group compared with the unprovoked seizure group (median 6.1 mm vs. 5.2 mm, P<.001). The cut-off value of ONSD higher than 5.61 was significantly associated with the prediction of the provoked seizure (P<.001). The area under the curve value was 0.882 (95% CI: 0.830-0.922) with a sensitivity of 86.5 and specificity of 78.9%.

CONCLUSIONS: Bedside ONSD measurement by means of ocular ultrasound is an effective method for differentiating provoked seizure from unprovoked seizure.

LIMITATIONS: Statistical significance of age on ONSD and exclusion of pediatric patients.

CONFLICT OF INTEREST: None.

PMID:36739503 | DOI:10.5144/0256-4947.2023.42

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Nevin Manimala Statistics

The combined impact of hyponatremia and hematocrit on the risk for 90-day readmission and death in patients with heart failure: dilutional hyponatremia versus depletional hyponatremia

Ann Saudi Med. 2023 Jan-Feb;43(1):17-24. doi: 10.5144/0256-4947.2023.17. Epub 2023 Feb 2.

ABSTRACT

BACKGROUND: Hyponatremia is common in hospitalized patients with heart failure (HF) and predicts a poor prognosis after discharge. In general, hyponatremia can be divided into two types: dilutional or depletional.

OBJECTIVE: Assess the impact of hyponatremia type on short-term outcomes.

DESIGN: Retrospective cohort SETTINGS: Single center in China PATIENTS AND METHODS: We sorted patients by hyponatremia into two types: dilutional hyponatremia (DiH, with hematocrit <35%) and depletional hyponatremia (DeH, with hematocrit ≥35%). The Kaplan-Meier method and Cox regression analysis were used to identify the impact of hyponatremia types on the risk for 90-day readmission and death.

MAIN OUTCOME MEASURES: 90-day readmission and death combined.

SAMPLE SIZE: 1770 patients.

RESULTS: Hyponatremia was present in 324/1770 patients with 182 cases classified as DiH versus 142 as DeH. Kaplan-Meier analyses showed a higher incidence of poor short-term outcomes in hyponatremia compared with normonatremia (log-rank P<.001), and the risk was higher in DiH than DeH although the difference was not statistically significant (log-rank P=.656). Multivariate Cox regression analyses showed that only DiH was independently associated with short-term outcomes (HR=1.34, 95%CI: 1.02-1.77, P=.038), but not DeH (HR=1.32, 95%CI: 0.97-1.80, P=.081). Analysis of the secondary endpoints showed that DiH increased the risk of readmission but not death (HR=1.36, P=.035 for readmission; HR=1.13, P=.831 for all-cause death).

CONCLUSIONS: Low hematocrit, rather than high hematocrit, with hyponatremia was associated with a risk of 90-day readmission in patients with HF.

LIMITATIONS: Single center, nonrandomized.

CONFLICT OF INTEREST: None.

PMID:36739500 | DOI:10.5144/0256-4947.2023.17

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Nevin Manimala Statistics

Dependence of clinical outcomes on time of hospital admission in patients with ST-segment elevation myocardial infarction

Ann Saudi Med. 2023 Jan-Feb;43(1):25-34. doi: 10.5144/0256-4947.2023.25. Epub 2023 Feb 2.

ABSTRACT

BACKGROUND: There are conflicting results in studies investigating the effects of percutaneous coronary intervention (PCI) on the prognosis of patients with ST-segment elevation myocardial infarction (STEMI) during or outside of usual hospital working hours. While some researchers have reported higher mortality rates in STEMI patients admitted outside of working hours, others did not find a statistically significant difference.

OBJECTIVES: Investigate the short-term endpoints and long-term outcomes of STEMI patients by time of admission.

DESIGN: Retrospective SETTING: Tertiary percutaneous coronary intervention center.

PATIENTS AND METHODS: Patients were grouped by admission, which consisted of four intervals: 06:00 to <12:00, 12:00 to <18:00, 18:00 to <24:00, and 24:00 to <06:00. We analyzed demographic, clinical and mortality by admission time interval and mortality by multivariate analyses, including the time intervals.

MAIN OUTCOME MEASURES: Clinical data and mortality SAMPLE SIZE: 735 patients; median (IQR) age 62 (22) years; 215 (29.3%) women.

RESULTS: Patients admitted at night were 1.37 times more likely to experience pulmonary edema than patients whose symptoms started in the daytime (P=.012); 32.9% of the patients whose symptoms started at night presented with Killip class II-IV, while during the daytime, 21.4% presented with Killip class II-IV (P=.001). Among the patients, the most common was inferior STEMI (38.6%). However, no-reflow was significantly higher during the daytime compared to the nighttime (P=.12). The risk of the cardiac arrest on admission was 1.2 times higher in patients admitted at night (P=.034). Neither time interval of admission nor several other variables had an effect on clinical outcome or mortality.

CONCLUSIONS: While patients admitted at night presented with pulmonary edema and cardiogenic shock more frequently, no reflow was observed during the day after the procedure. Although patients admitted at night with STEMI presented with worse clinical conditions, similar results were observed between the groups in clinical outcomes.

LIMITATIONS: More “real world” results might have been obtained if the study had replicated more typical referral conditions for PCI.

CONFLICT OF INTEREST: None.

PMID:36739499 | DOI:10.5144/0256-4947.2023.25