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Nevin Manimala Statistics

The tools at our hand to ensure the highest quality, systematicity, transparency and trustworthiness of clinical practice guidelines

United European Gastroenterol J. 2022 May 6. doi: 10.1002/ueg2.12241. Online ahead of print.

ABSTRACT

The current issue of the United European Gastroenterology Journal builds on its previous dedication to guidelines and guideline methods by introducing the AGREE-S methodological guide, an AGREE II extension for surgical interventions. The AGREE-S focuses on ensuring the quality of guidelines that specifically target surgical interventions with their characteristic challenges. Mainly to be used to aid completeness and transparency of de novo development of recommendations, it is also highly valuable in the process of adoption, adaptation or adolopment of existing surgical guidelines. The AGREE-S methodological guide with its aim to assist in guideline development is further enhanced by a reporting checklist (to increase transparency) and appraisal tool (to assess guideline quality) available at https://agree-s.org/.

PMID:35524418 | DOI:10.1002/ueg2.12241

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Effects of Cholesterol and PIP2 on Interactions between Glycophorin A and Band 3 in Lipid Bilayers

Biophys J. 2022 May 5:S0006-3495(22)00368-X. doi: 10.1016/j.bpj.2022.05.001. Online ahead of print.

ABSTRACT

In the erythrocyte membrane, the interactions between Glycophorin A (GPA) and Band 3 are associated strongly with the biological function of the membrane and several blood disorders. In this work, using coarse-grained molecular dynamics simulation, we systematically investigate the effects of cholesterol and phosphatidylinositol-4,5-bisphosphate (PIP2) on the interactions of GPA with Band 3 in the model erythrocyte membranes. We examine the dynamics of the interactions of GPA with Band 3 in different lipid bilayers on the microsecond time scale and calculate the binding free energy between GPA and Band 3. The results indicate that cholesterols thermodynamically favor the binding of GPA to Band 3 by increasing the thickness of the lipid bilayer and by producing an effective attraction between the proteins due to the depletion effect. Cholesterols also slow the kinetics of the binding of GPA to Band 3 by reducing the lateral mobility of the lipids and proteins and may influence the binding sites between the proteins. The anionic PIP2 lipids prefer binding to the surface of the proteins through electrostatic attraction between the PIP2 headgroup and the positively charged residues on the protein surface. Ions in the solvent facilitate the PIP2 aggregation which promotes the binding of GPA to Band 3.

PMID:35524411 | DOI:10.1016/j.bpj.2022.05.001

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Estimation of the COVID-19 Mean Incubation Time: Systematic Review, Meta-analysis, and Sensitivity Analysis

J Med Virol. 2022 May 6. doi: 10.1002/jmv.27841. Online ahead of print.

ABSTRACT

OBJECTIVES: Providing sensible estimates of the mean incubation time for COVID-19 is important yet complex. This study aims to provide sensible estimates of the mean incubation time of COVID-19 by capitalizing on available estimates reported in the literature and exploring different ways to accommodate heterogeneity involved in the reported studies.

METHODS: Online databases between January 1 of 2020 and May 20 of 2021 are first searched to obtain estimates of the mean incubation time of COVID-19 from available studies, and meta-analyses are then conducted to generate synthetic estimates. Heterogeneity of the studies is examined via the use of Cochran’s Q statistic and Higgin’s & Thompson’s I2 statistic, and subgroup analyses are conducted using mixed effects models. The publication bias issue is assessed using the funnel plot and Egger’s test.

RESULTS: Using all those reported mean incubation estimates for COVID-19, the mean incubation time is estimated to be 6.43 days with a 95% confidence interval (CI) (5.90, 6.96), and using all those reported mean incubation estimates together with those transformed median incubation estimates, the estimated mean incubation time is 6.07 days with a 95% CI (5.70,6.45).

CONCLUSIONS: The reported estimates of the mean incubation time of COVID-19 vary considerably due to multiple reasons, including heterogeneity and publication bias. To alleviate these issues, we take different angles to provide a sensible estimate of the mean incubation time of COVID-19. Our analyses show that the mean incubation time of COVID-19 between January 1 of 2020 and May 20 of 2021 ranges from 5.68 days to 8.30 days. This article is protected by copyright. All rights reserved.

PMID:35524338 | DOI:10.1002/jmv.27841

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Pain catastrophising, body mass index and depressive symptoms are associated with pain severity in tertiary referral orthopaedic foot/ankle patients

J Foot Ankle Res. 2022 May 6;15(1):32. doi: 10.1186/s13047-022-00536-5.

ABSTRACT

INTRODUCTION: Patients with chronic foot/ankle pain are often referred for orthopaedic assessment. Psychological vulnerabilities influence pain states (including foot and ankle), therefore this study aimed to establish the prevalence and relative importance of compromised psychological health to perceived foot/ankle pain severity in people referred to an orthopaedic foot and ankle clinic with non-urgent presentations.

METHODS: Patients with triaged non-urgent foot/ankle referrals to the Department of Orthopaedics at Gold Coast University Hospital were recruited over a 12-month period and completed the Manchester-Oxford Foot and Ankle Questionnaire which was the primary measure. Participants also completed questionnaires assessing their anthropometric, demographic and health characteristics (Self-Administered Comorbidity Questionnaire) as well as measures of health-related quality of life (EuroQol-5-Dimensions-5-Level Questionnaire and EQ Visual Analogue Scale) and psychological health (Center for Epidemiological Studies-Depression scale, Pain Catastrophizing Scale and Central Sensitization Inventory). Descriptive statistics were used to summarise participant characteristics and a hierarchical multiple linear regression was employed to establish the extent to which psychological variables explain additional variance in foot/ankle pain severity beyond the effects of participant characteristics (age, sex, body mass index (BMI)).

RESULTS: One hundred and seventy-two adults were recruited ((64.0% female), median (IQR) age 60.9 (17.7) years and BMI 27.6 (7.5) kg/m2). Specific psychological comorbidities were prevalent including depressive symptoms (48%), central sensitisation (38%) and pain catastrophising (24%). Age, sex and BMI accounted for 11.7% of the variance in MOXFQ-index and psychological variables accounted for an additional 28.2%. Pain catastrophising was the most significant independent predictor of foot/ankle pain severity (accounting for 14.4% of variance), followed by BMI (10.7%) and depressive symptoms (2.3%).

CONCLUSIONS: This study demonstrated that specific psychological comorbidities and increased BMI are common in this cohort and that these factors are associated with the symptoms for which patients are seeking orthopaedic assessment. This knowledge should prompt clinicians to routinely consider the psychosocial components of patient presentations and develop non-operative and pre-operative treatment strategies which consider these factors with the goal of improving overall patient outcomes.

PMID:35524334 | DOI:10.1186/s13047-022-00536-5

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Exploring accommodations along the education to employment pathway for deaf and hard of hearing healthcare professionals

BMC Med Educ. 2022 May 6;22(1):345. doi: 10.1186/s12909-022-03403-w.

ABSTRACT

BACKGROUND: Deaf and hard of hearing (DHH) people are an underserved population and underrepresented among healthcare professionals. A major barrier to success for DHH healthcare professionals is obtaining effective accommodations during education and employment. Our objective: describe DHH individuals’ experiences with accommodations in healthcare education.

METHODS: We used an online survey and multipronged snowball sampling to recruit participants who identify as DHH and who had applied to a U.S. health professional school (regardless of acceptance status). One hundred forty-eight individuals representing multiple professions responded; 51 had completed their training. Over 80% had been accepted to, were currently enrolled, or had completed health professions schools or residency programs, and/or were employed. The survey included questions addressing experiences applying to health professions programs and employment; satisfaction with accommodations in school and training; having worked with a disability resource professional (DRP); and depression screening.

RESULTS: Use and type of accommodation varied widely. While in school, respondents reported spending a mean of 2.1 h weekly managing their accommodations. Only 50% were highly satisfied with the accommodations provided by their programs. Use of disability resource providers (DRPs) for accommodations was highest during school (56%) and less frequent during post-graduate training (20%) and employment (14%). Respondents who transitioned directly from school to employment (versus via additional training) were more satisfied with their accommodations during school and were more likely to find employment (p = 0.02). Seventeen respondents screened positive for risk of depression; a positive screen was statistically associated with lower school accommodation satisfaction.

CONCLUSIONS: DHH people study and practice across many health professions. While respondents were mostly successful in entering health professions programs, accommodation experiences and satisfaction varied. Satisfaction with accommodations was related to successful employment and wellness. Low satisfaction was associated with higher likelihood of depression symptoms. To increase representation in the workforce, healthcare professional schools, training programs, and employers should enhance support for the learning and working climates for people with disabilities.

PMID:35524331 | DOI:10.1186/s12909-022-03403-w

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Association between perceived harm of tobacco and intention to quit: a cross-sectional analysis of the Vietnam Global Adult Tobacco Survey

BMC Public Health. 2022 May 6;22(1):909. doi: 10.1186/s12889-022-13348-w.

ABSTRACT

BACKGROUND: Perception of harm plays an important role in predicting intention to quit-an integral part of the cessation process. Perception on harm from bamboo waterpipe tobacco was unknown, even the predominant of this type of tobacco use. This study investigated the effects of perceived harm from cigarette and bamboo waterpipe tobacco on intention to quit among adult male Vietnamese tobacco users.

METHODS: From the nationally-representative 2015 Global Adult Tobacco Survey, we included 1,351 adult males (≥ 18 years old) who used cigarettes, bamboo waterpipes, or both. Demographic characteristics, tobacco use behaviors, perceived harm from tobacco use, and regulation/policy exposure were measured. Effects of perceived harm from cigarette and bamboo waterpipe tobacco on intention to quit were assessed by logistic regression.

RESULTS: Intention to quit prevalence was 59.0%, 55.0%, and 58.4% for cigarette, waterpipe, and dual users, respectively. Tobacco users who perceived that “using cigarettes and/or waterpipe could cause severe illness” and “waterpipe use is less harmful than cigarette smoking”, had tobacco use bans at home, or were exposed to anti-smoking campaigns or encouragement to quit information were more likely to intend to quit. When analyzed by tobacco users, intention to quit was more likely for those users who perceived their tobacco product as more harmful than the other product type, although statistical significance was only observed for cigarette users.

CONCLUSIONS: Misperceptions regarding harm from tobacco use could negatively affect intention to quit. Dissemination of accurate information on the risks from all forms of tobacco use and enforcement of tobacco control policies are important for encouraging intention to quit.

PMID:35524326 | DOI:10.1186/s12889-022-13348-w

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Efficacy and safety of anlotinib with and without EGFR-TKIs or immunotherapy in the treatment of elder patients with non-small-cell lung cancer: a retrospective study

BMC Pulm Med. 2022 May 6;22(1):179. doi: 10.1186/s12890-022-01981-5.

ABSTRACT

BACKGROUND: Anlotinib is a multitarget tyrosine kinase inhibitor for treating patients with advanced non-small cell lung cancer (NSCLC). We aimed to assess the efficacy and safety of anlotinib in elder patients with advanced NSCLC.

METHODS: Elder patients with advanced NSCLC who received anlotinib were enrolled. They were all age ≥ 65 years and with demonstrated records of EGFR gene status. All patients had received treatment with anlotinib or immune checkpoint inhibitors (ICIs)/EGFR-TKIs. The efficacy was evaluated according to the efficacy evaluation criteria for solid tumors (RECIST 1.1). Common Adverse Events Evaluation Criteria (CTCAE 4.03) were used to evaluate adverse drug reactions.

RESULTS: A total of 91 patients were included in this study. We divided the patients into two groups (EGFR wild type: 60 patients; EGFR mutation: 31 patients). Among EGFR negative patients, the progression-free survival (PFS) for anlotinib monotherapy and anlotinib combination ICI therapy was 3.2 months and 5.0 months, respectively (P = 0.012). The difference in overall survival (OS) between monotherapy and combination therapy was also significant (9.5 vs. 18.4 months, respectively P = 0.010). Interestingly, we further analyzed differences between patients with hypertension and without hypertension, and found that hypertension was associated with better prognosis (5.7 vs. 1.4 months, P < 0.0001). In the EGFR mutation group, the PFS for anlotinib and EGFR-TKI combination treatment indicated better efficacy than that of anlotinib monotherapy (1.83 months vs. 7.03 months, respectively, P = 0.001). The median OS for monotherapy and combination therapy in the EGFR mutation group showed no statistical difference (28.34 months vs. 31.37 months, P = 0.223). The most common adverse reactions were hypertension, fatigue, and hand-foot syndrome, mainly of grade 1 or 2. No significant increase in adverse reactions was observed in patients ≥ 70 years of age.

CONCLUSIONS: Anlotinib treatment and combination regimens resulted in good efficacy and controllable adverse reactions in elder patients with advanced NSCLC.

PMID:35524294 | DOI:10.1186/s12890-022-01981-5

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Orthogonal array composite designs for drug combination experiments with applications for tuberculosis

Stat Med. 2022 May 6. doi: 10.1002/sim.9423. Online ahead of print.

ABSTRACT

The aim of this article is to provide an overview of the orthogonal array composite design (OACD) methodology, illustrate the various advantages, and provide a real-world application. An OACD combines a two-level factorial design with a three-level orthogonal array and it can be used as an alternative to existing composite designs for building response surface models. We compare the D$$ D $$ -efficiencies of OACDs relative to the commonly used central composite design (CCD) when there are a few missing observations and demonstrate that OACDs are more robust to missing observations for two scenarios. The first scenario assumes one missing observation either from one factorial point or one additional point. The second scenario assumes two missing observations either from two factorial points or from two additional points, or from one factorial point and one additional point. Furthermore, we compare OACDs and CCDs in terms of I$$ I $$ -optimality for precise predictions. Lastly, a real-world application of an OACD for a tuberculosis drug combination study is provided.

PMID:35524290 | DOI:10.1002/sim.9423

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Quantitative methods used to evaluate impact of health promotion interventions to prevent HIV infections: a methodological systematic review protocol

Syst Rev. 2022 May 6;11(1):87. doi: 10.1186/s13643-022-01970-z.

ABSTRACT

BACKGROUND: Combination prevention is currently considered the best approach to combat HIV epidemic. It is based upon the combination of structural, behavioral, and biomedical interventions. Such interventions are frequently implemented in a health-promoting manner due to their aims, the approach that was adopted, and their complexity. The impact evaluation of these interventions often relies on methods inherited from the biomedical field. However, these methods have limitations and should be adapted to be relevant for these complex interventions. This systematic review aims to map the evidence-based methods used to quantify the impact of these interventions and analyze how these methods are implemented.

METHODS: Three databases (Web of Science, Scopus, PubMed) will be used to identify impact evaluation studies of health promotion interventions that aimed at reducing the incidence or prevalence of HIV infection. Only studies based on quantitative design assessing intervention impact on HIV prevalence or incidence will be included. Two reviewers will independently screen studies based on titles and abstracts and then on the full text. The information about study characteristics will be extracted to understand the context in which the interventions are implemented. The information specific to quantitative methods of impact evaluation will be extracted using items from the Mixed Methods Appraisal Tool (MMAT), the guidelines for reporting Statistical Analyses and Methods in the Published Literature (SAMPL), and the guidelines for Strengthening The Reporting of Empirical Simulation Studies (STRESS). This review will be conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement.

DISCUSSION: The impact evaluation of HIV prevention interventions is a matter of substantial importance given the growing need for evidence of the effectiveness of these interventions, whereas they are increasingly complex. These evaluations allow to identify the most effective strategies to be implemented to fight the epidemic. It is therefore relevant to map the methods to better implement them and adapt them according to the type of intervention to be evaluated.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020210825.

PMID:35524284 | DOI:10.1186/s13643-022-01970-z

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The anti-tumor effect of proteasome inhibitor MG132 for human adenoid cystic carcinoma: correlate with the emerging role of Nrf2/Keap1 signaling pathway

Head Face Med. 2022 May 6;18(1):15. doi: 10.1186/s13005-022-00318-1.

ABSTRACT

BACKGROUND: Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. Moreover, the unique biological characteristics and complex structures of ACC contribute to its poor survival rates. Recently, proteasome inhibitors have been shown to elicit satisfactory therapeutic effects in the treatment of certain solid tumors, but few studies have been implemented to investigate the effects of proteasome inhibitor therapy for ACC.

METHODS: In this present study, cell counting kit-8 assay and flow cytometry assay were performed to examine the effects of proteasome inhibitor (MG132) on cell viability and apoptosis. We applied western blot and immunofluorescence staining to explore the expression of the Nrf2/Keap1 signaling pathway and P62, additionally Nrf2 inhibitor (ML385) was utilized to evaluate the role of Nrf2/Keap1 signaling pathway in MG132-induced cell apoptosis.

RESULTS: Our data indicated that MG132 significantly suppressed the growth of ACC-83 cells(MG132 10µM P = 0.0046; 40µM P = 0.0033; 70µM P = 0.0007 versus control) and induced apoptosis (MG132 10µM P = 0.0458; 40µM P = 0.0018; 70µM P = 0.0087 versus control). The application of MG132 induced the up-regulation of Nrf2/Keap1 signaling pathway. Furthermore, inhibition of Nrf2 attenuated the therapeutic effects of MG132 for ACC (both ML385 + MG132 10µM P = 0.0013; 40µM P = 0.0057; 70µM P = 0.0003 versus MG132). P < 0.05 was considered statistically significant.

CONCLUSIONS: Our results revealed that proteasome inhibitors MG132 could inhibit the cell viability and induce the apoptosis of ACC through Nrf2/Keap1 signaling pathway.

PMID:35524269 | DOI:10.1186/s13005-022-00318-1