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Nevin Manimala Statistics

Exploring genotype by environment interaction on cassava yield and yield related traits using classical statistical methods

PLoS One. 2022 Jul 18;17(7):e0268189. doi: 10.1371/journal.pone.0268189. eCollection 2022.

ABSTRACT

Variety advancement decisions for root quality and yield-related traits in cassava are complex due to the variable patterns of genotype-by-environment interactions (GEI). Therefore, studies focused on the dissection of the existing patterns of GEI using linear-bilinear models such as Finlay-Wilkinson (FW), additive main effect and multiplicative interaction (AMMI), and genotype and genotype-by-environment (GGE) interaction models are critical in defining the target population of environments (TPEs) for future testing, selection, and advancement. This study assessed 36 elite cassava clones in 11 locations over three cropping seasons in the cassava breeding program of IITA based in Nigeria to quantify the GEI effects for root quality and yield-related traits. Genetic correlation coefficients and heritability estimates among environments found mostly intermediate to high values indicating high correlations with the major TPE. There was a differential clonal ranking among the environments indicating the existence of GEI as also revealed by the likelihood ratio test (LRT), which further confirmed the statistical model with the heterogeneity of error variances across the environments fit better. For all fitted models, we found the main effects of environment, genotype, and interaction significant for all observed traits except for dry matter content whose GEI sensitivity was marginally significant as found using the FW model. We identified TMS14F1297P0019 and TMEB419 as two topmost stable clones with a sensitivity values of 0.63 and 0.66 respectively using the FW model. However, GGE and AMMI stability value in conjunction with genotype selection index revealed that IITA-TMS-IBA000070 and TMS14F1036P0007 were the top-ranking clones combining both stability and yield performance measures. The AMMI-2 model clustered the testing environments into 6 mega-environments based on winning genotypes for fresh root yield. Alternatively, we identified 3 clusters of testing environments based on genotypic BLUPs derived from the random GEI component.

PMID:35849556 | DOI:10.1371/journal.pone.0268189

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Nevin Manimala Statistics

Virtual Reality in Treatment for Psychological Problems in First-Line Health care Professionals Fighting COVID-19 Pandemic: A Case Series

J Nerv Ment Dis. 2022 Jul 13. doi: 10.1097/NMD.0000000000001531. Online ahead of print.

ABSTRACT

Virtual reality therapy (VRT) is a new psychotherapeutic approach integrating virtual reality technology and psychotherapy. This case series aimed to study effectiveness of VRT in treating psychological problems. We described four cases of first-line health care professionals with emerging clinically significant early psychological problems during the COVID-19 outbreak, and specifically received the VRT treatment. We compared the Patient Health Questionnaire 9 items (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), PHQ-15, and Athens Insomnia Scale to evaluate psychological symptoms and sleep quality before and after sessions. All four cases showed a reduction in scale comparison. General scores of the PHQ-9 reduced 65%, GAD-7 reduced 52.17%, PHQ-15 decreased 38.17%, and scores of the Athens Insomnia Scale reduced 67.44%. Meanwhile, a reduction in depression, anxiety, psychosomatic, and sleeping symptoms was also found, which decreased 76.92% in general. These results are highly significant statistically. This case series demonstrated the effectiveness of VRT on psychological problems as a promising approach to apply on various psychological distress and disorders.

PMID:35849536 | DOI:10.1097/NMD.0000000000001531

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Nevin Manimala Statistics

A 30-Day Adjunct Wellness Intervention for the Management of Extra-Articular Symptoms of Rheumatoid Arthritis: A Formative Study

J Evid Based Integr Med. 2022 Jan-Dec;27:2515690X221113330. doi: 10.1177/2515690X221113330.

ABSTRACT

Individuals with rheumatoid arthritis (RA) continually fall short of treatment targets using standard drug therapies alone. There is growing evidence that emphasizing physical and mental wellness is equally crucial for improving functioning among people with RA. The purpose of this formative study is to examine the feasibility of offering the wellness-based intervention (“KickStart30”) in patients with RA. Thirteen individuals with RA on targeted immune modulators (a biologic or JAK inhibitor) enrolled in the KickStart30 program. Participants completed self-report measures of RA-specific disability (eg, pain) and other functional areas (eg, mood) in a pre- versus post- intervention design. Paired samples t-tests (and Related-Samples Wilcoxon Signed Rank Tests for non-normal distributions) detected statistically significant results for 10 of 12 measures, including reductions in pain (M = 4.54 to M = 3.54; p = .025; BPI), functional disability (M = 0.94 to M = 0.73, p = .032; HAQ-II), cognitive and physical dysfunction (M = 25.46 to M = 13.54, p < .001; CPFQ), depressive symptoms (M = 9.31 to M = 5.54, p = .003; PHQ-9), anxiety (M = 5.69 to M = 3.23, p = .005; GAD-7), insomnia (M = 11.62 to M = 17.32, p = .007; Note: higher scores on the SCI indicate less insomnia), stress-related eating (M = 75.46 to M = 84.54, p = .021; Note: higher scores on the EADES indicate less stress-related eating), along with significant increases in mindfulness (M = 62.54 to M = 67.85, p = .040; MAAS), mental wellness (M = 4.46 to M = 5.69; HERO), and well-being (Md = 8.00 to Md = 5.00, p = .004; WHO-5). All significant measures had medium to large effect sizes (Cohen’s d). The study gives preliminary support for the possibility that the adjunct intervention may have an effect.

PMID:35849439 | DOI:10.1177/2515690X221113330

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Nevin Manimala Statistics

Identifying Family and Unpaid Caregivers in Electronic Health Records: Descriptive Analysis

JMIR Form Res. 2022 Jul 18;6(7):e35623. doi: 10.2196/35623.

ABSTRACT

BACKGROUND: Most efforts to identify caregivers for research use passive approaches such as self-nomination. We describe an approach in which electronic health records (EHRs) can help identify, recruit, and increase diverse representations of family and other unpaid caregivers.

OBJECTIVE: Few health systems have implemented systematic processes for identifying caregivers. This study aimed to develop and evaluate an EHR-driven process for identifying veterans likely to have unpaid caregivers in a caregiver survey study. We additionally examined whether there were EHR-derived veteran characteristics associated with veterans having unpaid caregivers.

METHODS: We selected EHR home- and community-based referrals suggestive of veterans’ need for supportive care from friends or family. We identified veterans with these referrals across the 8 US Department of Veteran Affairs medical centers enrolled in our study. Phone calls to a subset of these veterans confirmed whether they had a caregiver, specifically an unpaid caregiver. We calculated the screening contact rate for unpaid caregivers of veterans using attempted phone screening and for those who completed phone screening. The veteran characteristics from the EHR were compared across referral and screening groups using descriptive statistics, and logistic regression was used to compare the likelihood of having an unpaid caregiver among veterans who completed phone screening.

RESULTS: During the study period, our EHR-driven process identified 12,212 veterans with home- and community-based referrals; 2134 (17.47%) veteran households were called for phone screening. Among the 2134 veterans called, 1367 (64.06%) answered the call, and 813 (38.1%) veterans had a caregiver based on self-report of the veteran, their caregiver, or another person in the household. The unpaid caregiver identification rate was 38.1% and 59.5% among those with an attempted phone screening and completed phone screening, respectively. Veterans had increased odds of having an unpaid caregiver if they were married (adjusted odds ratio [OR] 2.69, 95% CI 1.68-4.34), had respite care (adjusted OR 2.17, 95% CI 1.41-3.41), or had adult day health care (adjusted OR 3.69, 95% CI 1.60-10.00). Veterans with a dementia diagnosis (adjusted OR 1.37, 95% CI 1.00-1.89) or veteran-directed care referral (adjusted OR 1.95, 95% CI 0.97-4.20) were also suggestive of an association with having an unpaid caregiver.

CONCLUSIONS: The EHR-driven process to identify veterans likely to have unpaid caregivers is systematic and resource intensive. Approximately 60% (813/1367) of veterans who were successfully screened had unpaid caregivers. In the absence of discrete fields in the EHR, our EHR-driven process can be used to identify unpaid caregivers; however, incorporating caregiver identification fields into the EHR would support a more efficient and systematic identification of caregivers.

TRIAL REGISTRATION: ClincalTrials.gov NCT03474380; https://clinicaltrials.gov/ct2/show/NCT03474380.

PMID:35849430 | DOI:10.2196/35623

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The effects of wearing a mask on an exercise regimen

J Osteopath Med. 2022 Jul 14. doi: 10.1515/jom-2022-0045. Online ahead of print.

ABSTRACT

CONTEXT: Masks have long been utilized to prevent the spread of airborne pathogens and diseases in the healthcare setting. Recently, due to the COVID-19 pandemic, mask use has been expanded to all public areas to help slow the spread of this virus. One such location where masks can be seen is gyms. While exercising, the needs of the body are altered due to the increased stress being placed upon it. Normal physiology is thus adjusted to meet these new demands and to maintain optimal functioning. Therefore, it is possible that adding a mask covering the mouth and nose while exercising could further exacerbate this physiologic alteration, causing potential concerns.

OBJECTIVES: The goal of this study is to identify the impact of mask use on normal perceived physiology (breathing, heart rate, temperature, exertion, stamina, and quality of workout) within the exercising population.

METHODS: To obtain data focused on the research question, a self-reporting, online, anonymous Qualtrics survey was administered in local gyms and social media outlets. A total of 280 total participants were recruited between the ages of 18 and 65 who have ever exercised while wearing a mask. All results were analyzed utilizing descriptive statistics, bivariate correlations, Mann-Whitney U tests, and Kruskal-Wallis tests. A Cronbach’s alpha was also calculated to check internal validity. The significance level utilized was p≤0.05.

RESULTS: Completion of a Kruskal-Wallis test revealed statistical significance regarding the perception of masks in general and the participants’ rating of the perceived physiological parameters (breathing: p<0.001; heart rate: p<0.001; temperature: p<0.001; exertion: p<0.001; stamina: p<0.001; and quality of workout: p<0.001), the duration of time the mask was utilized during the workout, and the participants’ rating of the perceived physiological parameters (breathing: p=0.001; heart rate: p=0.020; temperature: p<0.001; exertion: p<0.001; stamina: p=0.001; quality of workout: p<0.001; and perception of mask: p<0.001), and the change in the number of days that the participants exercised per week during the pandemic as well as some of the participants’ ratings of the perceived physiological parameters (breathing: p=0.042; exertion: p=0.015; stamina: p=0.027; and quality of workout: p=0.016).

CONCLUSIONS: Any alterations to normal physiology perception while exercising with a mask appear to be psychological and adaptive in nature. Masks alone did not contribute to the perception of their physiologic changes.

PMID:35849419 | DOI:10.1515/jom-2022-0045

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Nevin Manimala Statistics

Patient and Clinician Decision Support to Increase Genetic Counseling for Hereditary Breast and Ovarian Cancer Syndrome in Primary Care: A Cluster Randomized Clinical Trial

JAMA Netw Open. 2022 Jul 1;5(7):e2222092. doi: 10.1001/jamanetworkopen.2022.22092.

ABSTRACT

IMPORTANCE: To promote the identification of women carrying BRCA1/2 variants, the US Preventive Services Task Force recommends that primary care clinicians screen asymptomatic women for an increased risk of carrying a BRCA1/2 variant risk.

OBJECTIVE: To examine the effects of patient and clinician decision support about BRCA1/2 genetic testing compared with standard education alone.

DESIGN, SETTING, AND PARTICIPANTS: This clustered randomized clinical trial was conducted at an academic medical center including 67 clinicians (unit of randomization) and 187 patients. Patient eligibility criteria included women aged 21 to 75 years with no history of breast or ovarian cancer, no prior genetic counseling or testing for hereditary breast and ovarian cancer syndrome (HBOC), and meeting family history criteria for BRCA1/2 genetic testing.

INTERVENTIONS: RealRisks decision aid for patients and the Breast Cancer Risk Navigation Tool decision support for clinicians. Patients scheduled a visit with their clinician within 6 months of enrollment.

MAIN OUTCOMES AND MEASURES: The primary end point was genetic counseling uptake at 6 months. Secondary outcomes were genetic testing uptake at 6 and 24 months, decision-making measures (perceived breast cancer risk, breast cancer worry, genetic testing knowledge, decision conflict) based upon patient surveys administered at baseline, 1 month, postclinic visit, and 6 months.

RESULTS: From December 2018 to February 2020, 187 evaluable patients (101 in the intervention group, 86 in the control group) were enrolled (mean [SD] age: 40.7 [13.2] years; 88 Hispanic patients [46.6%]; 15 non-Hispanic Black patients [8.1%]; 72 non-Hispanic White patients [38.9%]; 35 patients [18.9%] with high school education or less) and 164 (87.8%) completed the trial. There was no significant difference in genetic counseling uptake at 6 months between the intervention group (20 patients [19.8%]) and control group (10 patients [11.6%]; difference, 8.2 percentage points; OR, 1.88 [95% CI, 0.82-4.30]; P = .14). Genetic testing uptake within 6 months was also statistically nonsignificant (13 patients [12.9%] in the intervention group vs 7 patients [8.1%] in the control group; P = .31). At 24 months, genetic testing uptake was 31 patients (30.7%) in intervention vs 18 patients (20.9%) in control (P = .14). Comparing decision-making measures between groups at baseline to 6 months, there were significant decreases in perceived breast cancer risk and in breast cancer worry (standard mean differences = -0.48 and -0.40, respectively).

CONCLUSIONS AND RELEVANCE: This randomized clinical trial did not find a significant increase in genetic counseling uptake among patients who received patient and clinician decision support vs those who received standard education, although more than one-third of the ethnically diverse women enrolled in the intervention underwent genetic counseling. These findings suggest that the main advantage for these high-risk women is the ability to opt for screening and preventive services to decrease their cancer risk.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03470402.

PMID:35849397 | DOI:10.1001/jamanetworkopen.2022.22092

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Evaluation of telephone triage among chest pain patients in out-of-hours primary care in the Netherlands (TRACE)

Fam Pract. 2022 Jul 18:cmac077. doi: 10.1093/fampra/cmac077. Online ahead of print.

ABSTRACT

BACKGROUND: Telephone triage is fully integrated in Dutch out-of-hours primary care (OOH-PC). Patients presenting with chest pain are initially assessed according to a standardized protocol (“Netherlands Triage Standard” [NTS]). Nevertheless, little is known about its (diagnostic) performance, nor on the impact of subsequent clinical judgements made by triage assistants and general practitioners (GPs).

OBJECTIVE: To evaluate the performance of the current NTS chest pain protocol.

METHODS: Observational, retrospective cohort study of adult patients with chest pain who contacted a regional OOH-PC facility in the Netherlands, in 2017. The clinical outcome measure involved the occurrence of a “major event,” which is a composite of all-cause mortality and urgent cardiovascular and noncardiovascular conditions, occurring ≤6 weeks of initial contact. We assessed the performance using diagnostic and discriminatory properties.

RESULTS: In total, 1,803 patients were included, median age was 54.0 and 57.5% were female. Major events occurred in 16.2% of patients with complete follow-up, including 99 (6.7%) cases of acute coronary syndrome and 22 (1.5%) fatal events. NTS urgency assessment showed moderate discriminatory abilities for predicting major events (c-statistic 0.66). Overall, NTS performance showed a sensitivity and specificity of 83.0% and 42.4% with a 17.0% underestimated major event rate. Triage assistants’ revisions hardly improved urgency allocation. Further consideration of the clinical course following OOH-PC contact did generate a more pronounced improvement with a sensitivity of 89.4% and specificity of 61.9%.

CONCLUSION: Performance of telephone triage of chest pain appears moderate at best, with acceptable safety yet limited efficiency, even after including further work-up by GPs.

PMID:35849343 | DOI:10.1093/fampra/cmac077

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Role of EXO1 nuclease activity in genome maintenance, the immune response and tumor suppression in Exo1D173A mice

Nucleic Acids Res. 2022 Jul 18:gkac616. doi: 10.1093/nar/gkac616. Online ahead of print.

ABSTRACT

DNA damage response pathways rely extensively on nuclease activity to process DNA intermediates. Exonuclease 1 (EXO1) is a pleiotropic evolutionary conserved DNA exonuclease involved in various DNA repair pathways, replication, antibody diversification, and meiosis. But, whether EXO1 facilitates these DNA metabolic processes through its enzymatic or scaffolding functions remains unclear. Here, we dissect the contribution of EXO1 enzymatic versus scaffolding activity by comparing Exo1DA/DA mice expressing a proven nuclease-dead mutant form of EXO1 to entirely EXO1-deficient Exo1-/- and EXO1 wild type Exo1+/+ mice. We show that Exo1DA/DA and Exo1-/- mice are compromised in canonical DNA repair processing, suggesting that the EXO1 enzymatic role is important for error-free DNA mismatch and double-strand break repair pathways. However, in non-canonical repair pathways, EXO1 appears to have a more nuanced function. Next-generation sequencing of heavy chain V region in B cells showed the mutation spectra of Exo1DA/DA mice to be intermediate between Exo1+/+ and Exo1-/- mice, suggesting that both catalytic and scaffolding roles of EXO1 are important for somatic hypermutation. Similarly, while overall class switch recombination in Exo1DA/DA and Exo1-/- mice was comparably defective, switch junction analysis suggests that EXO1 might fulfill an additional scaffolding function downstream of class switching. In contrast to Exo1-/- mice that are infertile, meiosis progressed normally in Exo1DA/DA and Exo1+/+ cohorts, indicating that a structural but not the nuclease function of EXO1 is critical for meiosis. However, both Exo1DA/DA and Exo1-/- mice displayed similar mortality and cancer predisposition profiles. Taken together, these data demonstrate that EXO1 has both scaffolding and enzymatic functions in distinct DNA repair processes and suggest a more composite and intricate role for EXO1 in DNA metabolic processes and disease.

PMID:35849338 | DOI:10.1093/nar/gkac616

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The statistical foundation of the reference population for semen analysis included in the sixth edition of the WHO manual: a critical reappraisal of the evidence

Hum Reprod. 2022 Jul 18:deac161. doi: 10.1093/humrep/deac161. Online ahead of print.

ABSTRACT

In the most recent version of the ‘WHO Laboratory Manual For The Examination And Processing Of Human Semen’, the updated target population used to infer reference values included 3589 fertile subjects, representative of 12 countries and 5 continents, and 10 studies. We have critically evaluated the newly proposed distribution of semen examination results using an approach borrowed from clinical chemistry laboratories and based on the recommendations of the International Federation of Clinical Chemistry for estimation of reference intervals. Surprisingly, most prerequisites to produce common reference intervals through multicentric data were not met. Moreover, when we assessed with the bootstrap method the descriptive reference values obtained from raw data of the 10 individual studies for sperm concentration, sperm number, motility and normal forms, we found that none of the populations was completely correctly described by the reference centiles. We concluded that aggregated data used to build the reference distribution cannot be considered to originate from the same population, and this can result from real differences among individuals or different methodological approaches used in the various studies. Transferability conditions across studies did not seem to have been met. Our findings strengthen the relevance of concerns regarding the use of reference populations in the World Health Organization manual to discriminate between fertile and infertile men.

PMID:35849333 | DOI:10.1093/humrep/deac161

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Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Triple Therapy Compared with Other Therapies for the Treatment of COPD: A Network Meta-Analysis

Adv Ther. 2022 Jul 17. doi: 10.1007/s12325-022-02231-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Randomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting β2-agonist [LABA], and long-acting muscarinic antagonist [LAMA]) for the treatment of chronic obstructive pulmonary disease (COPD) are limited. This network meta-analysis (NMA) investigated the comparative efficacy of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus any triple (ICS/LABA/LAMA) combinations and dual therapies in patients with COPD.

METHODS: This NMA was conducted on the basis of a systematic literature review (SLR), which identified RCTs in adults aged at least 40 years with COPD. The RCTs compared different ICS/LABA/LAMA combinations or an ICS/LABA/LAMA combination with any dual therapy (ICS/LABA or LAMA/LABA). Outcomes of interest included forced expiratory volume in 1 s (FEV1), annualized rate of combined moderate and severe exacerbations, St George’s Respiratory Questionnaire (SGRQ) total score and SGRQ responders, transition dyspnea index focal score, and rescue medication use (RMU). Analyses were conducted at 24 weeks (primary endpoint), and 12 and 52 weeks (if feasible).

RESULTS: The NMA was informed by five trials reporting FEV1 at 24 weeks. FF/UMEC/VI was statistically significantly more effective at increasing trough FEV1 (based on change from baseline) than all triple comparators in the network apart from UMEC + FF/VI. The NMA was informed by 17 trials reporting moderate or severe exacerbation endpoints. FF/UMEC/VI demonstrated statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus single-inhaler budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR). At 24 weeks, the NMA was informed by five trials. FF/UMEC/VI showed statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus UMEC + FF/VI and BUD/GLY/FOR. FF/UMEC/VI also demonstrated improvements in mean SGRQ score versus other triple therapy comparators at 24 weeks, and a significant reduction in RMU compared with BUD/GLY/FOR (160/18/9.6).

CONCLUSION: The findings of this NMA suggest favorable efficacy with single-inhaler triple therapy comprising FF/UMEC/VI. Further analysis is required as additional evidence becomes available.

PMID:35849317 | DOI:10.1007/s12325-022-02231-0