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Nevin Manimala Statistics

A quantitative theory for genomic offset statistics

Mol Biol Evol. 2023 Jun 12:msad140. doi: 10.1093/molbev/msad140. Online ahead of print.

ABSTRACT

Genomic offset statistics predict the maladaptation of populations to rapid habitat alteration based on association of genotypes with environmental variation. Despite substantial evidence for empirical validity, genomic offset statistics have well-identified limitations, and lack a theory that would facilitate interpretations of predicted values. Here, we clarified the theoretical relationships between genomic offset statistics and unobserved fitness traits controlled by environmentally selected loci, and proposed a geometric measure to predict fitness after rapid change in local environment. The predictions of our theory were verified in computer simulations and in empirical data on African pearl millet (Cenchrus americanus) obtained from a common garden experiment. Our results proposed a unified perspective on genomic offset statistics, and provided a theoretical foundation necessary when considering their potential application in conservation management in the face of environmental change.

PMID:37307566 | DOI:10.1093/molbev/msad140

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Nevin Manimala Statistics

Versatile detection of diverse selective sweeps with Flex-sweep

Mol Biol Evol. 2023 Jun 12:msad139. doi: 10.1093/molbev/msad139. Online ahead of print.

ABSTRACT

Understanding the impacts of selection pressures influencing modern-day genomic diversity is a major goal of evolutionary genomics. In particular, the contribution of selective sweeps to adaptation remains an open question, with persistent statistical limitations on the power and specificity of sweep detection methods. Sweeps with subtle genomic signals have been particularly challenging to detect. While many existing methods powerfully detect specific types of sweeps and/or those with strong signals, their power comes at the expense of versatility. We present Flex-sweep, a machine learning-based tool designed to detect sweeps with a variety of subtle signals, including those thousands of generations old. It is especially valuable for non-model organisms, for which we have neither expectations about the overall characteristics of sweeps nor outgroups with population-level sequencing to otherwise facilitate detecting very old sweeps. We show that Flex-sweep has the power to detect sweeps with subtle signals, even in the face of demographic model misspecification, recombination rate heterogeneity, and background selection. Flex-sweep detects sweeps up to 0.125 * 4Ne generations old, including those that are weak, soft, and/or incomplete; it can also detect strong, complete sweeps up to 0.25 * 4Ne generations old. We apply Flex-sweep to the 1000 Genomes Yoruba data set and, in addition to recovering previously identified sweeps, show that sweeps disproportionately occur within genic regions and close to regulatory regions. In addition, we show that virus-interacting proteins (VIPs) are strongly enriched for selective sweeps, recapitulating previous results that demonstrate the importance of viruses as a driver of adaptive evolution in humans.

PMID:37307561 | DOI:10.1093/molbev/msad139

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Nevin Manimala Statistics

Utility of Regional Maxillary Nerve Blocks in Improving Cleft Palate Postoperative Outcomes

J Craniofac Surg. 2023 Jun 12. doi: 10.1097/SCS.0000000000009464. Online ahead of print.

ABSTRACT

BACKGROUND: Palatoplasty procedures used to repair cleft palates are commonly associated with limiting postoperative pain. Regional anesthetic blocks have been utilized to improve pain outcomes and decrease opioid intake, yet additional data is needed to fully explore its utility in this setting.

OBJECTIVE: To explore whether ultrasound-guided suprazygomatic maxillary blocks (SMB) improve postoperative pain, postoperative opioid use, time to oral feeding, and length of stay compared with a palatal field block in cleft palate repair.

METHODS: In this retrospective chart review, 47 patients aged 9 to 25 months who underwent cleft palate repair between 2013 and 2020 were allocated into 2 groups: a control group where patients received only palatal local anesthetic in a field block fashion (N=29), and Maxillary block group who received ultrasound-guided SMB (N=18). Patients were matched by age and cleft Veau type. The primary outcomes were total postoperative morphine equivalent consumption, average pain scores, length of stay, and time to first oral feed.

RESULTS: Comparing field block versus SMB groups, there was not a statistical difference in the overall dose of postoperative morphine equivalent opioid administration (11.71 vs. 13.36 mg; P=0.483), average pain scores (5.78 vs. 5.27; P=0.194), time to first oral feed [17.21 vs. 14.48 h; P=0.407, 95% CI: (-3.85, 9.32)] or length of stay (P=0.292).

CONCLUSION: The use of SMBs did not demonstrate a difference in the postoperative outcomes evaluated by this study. Further study is needed to define its utility in cleft palate repair.

PMID:37307540 | DOI:10.1097/SCS.0000000000009464

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Nevin Manimala Statistics

Pott’s Puffy: First Shot is the Best Shot

J Craniofac Surg. 2023 Jun 12. doi: 10.1097/SCS.0000000000009451. Online ahead of print.

ABSTRACT

OBJECTIVE: Low incidence of Pott’s Puffy tumor (PPT) has caused studying risk factors and recurrences of the disease to be difficult. We used the comparatively increased incidence at our institution to evaluate potential risk factors for the disease process itself and prognostic factors for recurrence of the disease.

METHODS: Single institutional retrospective chart review identified 31 patients from 2010 to 2022 with PPT compared with a control group of 20 patients with either chronic rhinosinusitis or recurrent sinusitis. Patient mean age of PPT was 42 (range of 5 to 90) with the majority of the patient population as male (74%) and Caucasian (68%) in the setting of rural West Texas. Patient mean age of the control group was 50.7 (range of 30-78) with majority of patient population as male (55%) and Caucasian (70%). Interventions studied were functional endoscopic sinus surgery (FESS), FESS with trephination, and cranialization with or without FESS to compare prognostic factors for recurrence rates of PPT. These patients’ prognostic risk factors for recurrence and risk factors to develop PPT were analyzed using Analysis of Variance (ANOVA) χ2 statistical analysis with Fischer exact testing.

RESULTS: Mean age was 42 years (range of 5-90) with the majority of the PPT patient population as male (74%) and Caucasian (68%) with an overall incidence of about 1 in 300,000. Pott’s Puffy tumor patients were significantly favored in the younger and male population compared with the control patients. Risk factors of no prior allergy diagnosis, previous trauma, medication allergy to penicillin class or cephalosporin class, and lower body mass index were significant in the PPT population compared with the control group. Significant prognostic factors for recurrence of PPT were prior history of sinus surgery and operative treatment choice. Fifty percent (3/6) of patients with prior sinus surgery had recurrence of PPT. Of our 4 treatment options (FESS, FESS with trephination, FESS with cranialization, or cranialization alone), ;FESS had a recurrence of PPT of 0% (0/13), FESS with trephination had a recurrence of PPT of 50% (3/6), FESS with cranialization had a recurrence of PPT of 11% (1/9), and cranizalization alone had a recurrence of PPT of 0% (0/3). Of note, postop chronic rhinosinusitis was seen in 46% (6/13) of FESS alone, 17% (1/6) with FESS with trephination, 0% (0/9) with FESS with cranialization, and 33% (1/3) with just cranialization alone.

CONCLUSIONS: Pott’s Puffy tumor patients were younger and predominately male when compared to the control patients. No prior allergy diagnosis, previous trauma history, medication allergy to penicillin class or cephalosporin class, and lower body mass index are risk factors for PPT. There are 2 prognostic factors that predict recurrence of PPT: first operative treatment choice and prior sinus surgery. History of prior sinus surgery tends to increase the recurrence of PPT. The first operative treatment plan is the best shot at definitively treating PPT. Correct management surgically can prevent recurrence of PPT as well as long-term recurrence of chronic rhinosinusitis. With early diagnosis and mild disease, FESS is sufficient to prevent recurrence of PPT but chronic sinusitis may continue to occur if frontal sinus outflow track is not well opened. If considering trephination, a definitive cranialization may be more suited for more advanced disease since our study showed 50% of recurrence of PPT with trephination and FESS along with 17% chronic sinusitis long term. More advanced diseases with higher WBCs and intracranial extension do better with more aggressive surgical management with a cranialization with or without FESS which shows to reduce rates of PPT recurrence significantly.

PMID:37307535 | DOI:10.1097/SCS.0000000000009451

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Nevin Manimala Statistics

The Efficacy of a Diet Low in Fermentable Oligo-, Di-, Monosaccharides, and Polyols in Irritable Bowel Syndrome Compared to Its “Real-world” Effectiveness: Protocol for a Systematic Review

JMIR Res Protoc. 2023 Jun 12;12:e41399. doi: 10.2196/41399.

ABSTRACT

BACKGROUND: Irritable bowel syndrome (IBS) is associated with various gastrointestinal and nongastrointestinal symptoms and reduced quality of life. A diet low in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) is one therapeutic option for IBS. Although the efficacy of the low FODMAP diet has been reported in several systematic reviews, the efficacy-effectiveness gap of the low FODMAP diet has not yet been assessed.

OBJECTIVE: This systematic review aims to compare the efficacy of the low FODMAP diet from efficacy randomized controlled trials (RCTs) with the effectiveness of studies conducted in “real-world” settings.

METHODS: RCTs, prospective and retrospective cohort studies, and retrospective audits assessing the low FODMAP diet in adults with IBS will be searched in 4 databases: Embase, MEDLINE, CENTRAL, and CINAHL. Two independent reviewers will perform study selection, data extraction, and risk of bias assessment and assess selected quality aspects from the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) protocol. Outcomes assessed are stool frequency, stool consistency, abdominal pain, overall symptom scores, adequate symptom relief, IBS-specific quality of life, and diet adherence. Data will be summarized with forest plots without summary statistics, tables, and narrative descriptions.

RESULTS: The search, title and abstract screening, and full-text screening were completed in March 2021, and an updated search was done in May 2022. As of May 2023, data analysis is almost finished, and manuscript writing is in progress. Submission of the manuscript is expected by July 2023.

CONCLUSIONS: The findings of this systematic review will compare the efficacy of the low FODMAP diet for IBS found in RCTs to the diet’s real-world effectiveness.

TRIAL REGISTRATION: PROSPERO CRD42021278952; https://tinyurl.com/32jk43ev.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41399.

PMID:37307063 | DOI:10.2196/41399

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Nevin Manimala Statistics

Consumers’ Needs for Laboratory Results Portals: Questionnaire Study

JMIR Hum Factors. 2023 Jun 12;10:e42843. doi: 10.2196/42843.

ABSTRACT

BACKGROUND: Over the last decade, there has been an increase in the number of health care consumers (ie, patients, citizens, and laypeople) with access to their laboratory results through portals. However, many portals are not designed with the consumer in mind, which can limit communication effectiveness and consumer empowerment.

OBJECTIVE: We aimed to study design facilitators and barriers affecting consumer use of a laboratory results portal. We sought to identify modifiable design attributes to inform future interface specifications and improve patient safety.

METHODS: A web-based questionnaire with open- and closed-ended items was distributed to consumers in British Columbia, Canada. Open-ended items with affinity diagramming and closed-ended questions with descriptive statistics were analyzed.

RESULTS: Participants (N=30) preferred reviewing their laboratory results through portals rather than waiting to see their provider. However, respondents were critical of the interface design (ie, interface usability, information completeness, and display clarity). Scores suggest there are display issues impacting communication that require urgent attention.

CONCLUSIONS: There are modifiable usability, content, and display issues associated with laboratory results portals that, if addressed, could arguably improve communication effectiveness, patient empowerment, and health care safety.

PMID:37307049 | DOI:10.2196/42843

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Nevin Manimala Statistics

New Web-Based System for Recording Public Health Nursing Practices and Determining Best Practices: Protocol of an Exploratory Sequential Design

JMIR Res Protoc. 2023 Jun 12;12:e45342. doi: 10.2196/45342.

ABSTRACT

BACKGROUND: Digitalization and information and communication technology (ICT) promote effective, efficient individual and community care. Clinical terminology or taxonomy and its framework visualize individual patients’ and nursing interventions’ classifications to improve their outcomes and care quality. Public health nurses (PHNs) provide lifelong individual care and community-based activities while developing projects to promote community health. The linkage between these practices and clinical assessment remains tacit. Owing to Japan’s lagging digitalization, supervisory PHNs face difficulties in monitoring each department’s activities and staff members’ performances and competencies. Randomly selected prefectural or municipal PHNs collect data on daily activities and required hours every 3 years. No study has adopted these data for public health nursing care management. PHNs need ICTs to manage their work and improve care quality; it may help identify health needs and suggest best public health nursing practices.

OBJECTIVE: We aim to develop and validate an electronic recording and management system for evaluating different public health nursing practice needs, including individual care, community-based activities, and project development, and for determining their best practices.

METHODS: We used a 2-phase exploratory sequential design (in Japan) comprising 2 phases. In phase 1, we developed the system’s architectural framework and a hypothetical algorithm to determine the need for practice review through a literature review and a panel discussion. We designed a cloud-based practice recording system, including a daily record system and a termly review system. The panels included 3 supervisors who were prior PHNs at the prefectural or municipal government, and 1 was the executive director of the Japanese Nursing Association. The panels agreed that the draft architectural framework and hypothetical algorithm were reasonable. The system was not linked to electronic nursing records to protect patient privacy. Phase 2 validated each item through interviews with supervisory PHNs using a web-based meeting system. A nationwide survey was distributed to supervisory and midcareer PHNs across local governments.

RESULTS: This study was funded in March 2022 and approved by all ethics review boards from July to September and November 2022. Data collection was completed in January 2023. Five PHNs participated in the interviews. In the nationwide survey, responses were obtained from 177 local governments of supervisory PHNs and 196 midcareer ones.

CONCLUSIONS: This study will reveal PHNs’ tacit knowledge about their practices, assess needs for different approaches, and determine best practices. Additionally, this study will promote ICT-based practices in public health nursing. The system will enable PHNs to record their daily activities and share them with their supervisors to reflect on and improve their performance, and the quality of care to promote health equity in community settings. The system will support supervisory PHNs in creating performance benchmarks for their staff and departments to promote evidence-based human resource development and management.

TRIAL REGISTRATION: UMIN-ICDR UMIN000049411; https://tinyurl.com/yfvxscfm.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45342.

PMID:37307040 | DOI:10.2196/45342

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Nevin Manimala Statistics

Add-on Rehmannia-6-Based Chinese Medicine in Type 2 Diabetes and CKD: A Multicenter Randomized Controlled Trial

Clin J Am Soc Nephrol. 2023 Jun 12. doi: 10.2215/CJN.0000000000000199. Online ahead of print.

ABSTRACT

BACKGROUND: Diabetes is the leading cause of chronic kidney disease (CKD) and kidney failure We assessed the real-world effectiveness of Rehmannia-6-based Chinese medicine treatment, the most used Chinese medicine formulation, on the change in estimated glomerular filtration rate (eGFR) and albuminuria in diabetic CKD patients with severely increased albuminuria.

METHODS: In this randomized, assessor-blind, standard care-controlled, parallel, multi-center trial, 148 adult patients from outpatient clinics with type 2 diabetes, estimated glomerular filtration rate (eGFR) of 30-90 ml/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) of 300-5000 mg/g were randomized 1:1 to a 48-week add-on protocolized Chinese medicine treatment program (using Rehmannia-6-based formulations in granule form taken orally) or standard care alone. Primary outcomes were the slope of change in eGFR and UACR between baseline and endpoint (48 weeks after randomization) in the intention-to-treat population. Secondary outcomes included safety, and the change in biochemistry, biomarkers and concomitant drug use.

RESULTS: The mean age, eGFR and UACR were 65 years, 56.7 ml/min/1.73m2 and 753 mg/g, respectively. 95% (n=141) of endpoint primary outcome measures were retrievable. For eGFR, the estimated slope of change was -2.0 (95%CI: -0.1 to -3.9) and -4.7 (95%CI: -2.9 to -6.5) ml/min/1.73m2 in participants treated with add-on Chinese medicine or standard care alone, resulting a 2.7 ml/min/1.73m2 per year (95%CI: 0.1 to 5.3, p=0.04) less decline with Chinese medicine. For UACR, the estimated proportion in the slope of change was 0.88 (0.75 to 1.02) and 0.99 (0.85 to 1.14) in participants treated with add-on Chinese medicine or standard care alone. The inter-group proportional difference (0.89, 11% slower increment in add-on Chinese medicine, 95%CI: 0.72 to 1.10, p=0.28) did not reach statistical significance. 85 adverse events were recorded from 50 participants (add-on Chinese medicine vs control: 22 (31%) vs 28 (36%)).

CONCLUSIONS: Rehmannia-6-based Chinese medicine treatment stabilized eGFR on top of standard care alone after 48 weeks in patients with type 2 diabetes, stage 2 to 3 chronic kidney disease and severely increased albuminuria.

CLINICAL TRIAL REGISTRY: Semi-individualised Chinese Medicine Treatment as an Adjuvant Management for Diabetic Nephropathy (SCHEMATIC), NCT02488252.

PMID:37307005 | DOI:10.2215/CJN.0000000000000199

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Nevin Manimala Statistics

Statistical and Conceptual Considerations in Socioepigenomics Research on Childhood Adversity and Epigenetic Aging

JAMA Netw Open. 2023 Jun 1;6(6):e2317958. doi: 10.1001/jamanetworkopen.2023.17958.

NO ABSTRACT

PMID:37307003 | DOI:10.1001/jamanetworkopen.2023.17958

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Nevin Manimala Statistics

Epidemiology of Cancer-Associated Venous Thromboembolism in Patients With Solid and Hematologic Neoplasms in the Veterans Affairs Health Care System

JAMA Netw Open. 2023 Jun 1;6(6):e2317945. doi: 10.1001/jamanetworkopen.2023.17945.

ABSTRACT

IMPORTANCE: Identifying changes in epidemiologic patterns of the incidence and risk of cancer-associated thrombosis (CAT), particularly with evolving cancer-directed therapy, is essential for risk stratification.

OBJECTIVE: To assess the incidence of CAT over time and to determine pertinent patient-specific, cancer-specific, and treatment-specific factors associated with its risk.

DESIGN, SETTING, AND PARTICIPANTS: This longitudinal, retrospective cohort study was conducted from 2006 to 2021. Duration of follow-up was from the date of diagnosis until first venous thromboembolism (VTE) event, death, loss of follow-up (defined as a 90-day gap without clinical encounters), or administrative censoring on April 1, 2022. The study took place within the US Department of Veterans Affairs national health care system. Patients with newly diagnosed invasive solid tumors and hematologic neoplasms were included in the study. Data were analyzed from December 2022 to February 2023.

EXPOSURE: Newly diagnosed invasive solid tumors and hematologic neoplasms.

MAIN OUTCOMES: Incidence of VTE was assessed using a combination of International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification and natural language processing confirmed outcomes. Cumulative incidence competing risk functions were used to estimate incidence of CAT. Multivariable Cox regression models were built to assess the association of baseline variables with CAT. Pertinent patient variables included demographics, region, rurality, area deprivation index, National Cancer Institute comorbidity index, cancer type, staging, first-line systemic treatment within 3 months (time-varying covariate), and other factors that could be associated with the risk of VTE.

RESULTS: A total of 434 203 patients (420 244 men [96.8%]; median [IQR] age, 67 [62-74] years; 7414 Asian or Pacific Islander patients [1.7%]; 20 193 Hispanic patients [4.7%]; 89 371 non-Hispanic Black patients [20.6%]; 313 157 non-Hispanic White patients [72.1%]) met the inclusion criteria. Overall incidence of CAT at 12 months was 4.5%, with yearly trends ranging stably from 4.2% to 4.7%. The risk of VTE was associated with cancer type and stage. In addition to confirming well-known risk distribution among patients with solid tumors, a higher risk of VTE was observed among patients with aggressive lymphoid neoplasms compared with patients with indolent lymphoid or myeloid hematologic neoplasms. Compared with no treatment, patients receiving first-line chemotherapy (hazard ratio [HR], 1.44; 95% CI, 1.40-1.49) and immune checkpoint inhibitors (HR, 1.49; 95% CI, 1.22-1.82) had a higher adjusted relative risk than patients receiving targeted therapy (HR, 1.21; 95% CI, 1.13-1.30) or endocrine therapy (HR, 1.20; 95% CI, 1.12-1.28). Finally, adjusted VTE risk was significantly higher among Non-Hispanic Black patients (HR, 1.23; 95% CI, 1.19-1.27) and significantly lower in Asian or Pacific Islander patients (HR, 0.84; 95% CI, 0.76-0.93) compared with Non-Hispanic White patients.

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with cancer, a high incidence of VTE was observed, with yearly trends that remained stable over the 16-year study period. Both novel and known factors associated with the risk of CAT were identified, providing valuable and applicable insights in this current treatment landscape.

PMID:37306999 | DOI:10.1001/jamanetworkopen.2023.17945