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Nevin Manimala Statistics

Variant-specific inflation factors for assessing population stratification at the phenotypic variance level

Nat Commun. 2021 Jun 9;12(1):3506. doi: 10.1038/s41467-021-23655-2.

ABSTRACT

In modern Whole Genome Sequencing (WGS) epidemiological studies, participant-level data from multiple studies are often pooled and results are obtained from a single analysis. We consider the impact of differential phenotype variances by study, which we term ‘variance stratification’. Unaccounted for, variance stratification can lead to both decreased statistical power, and increased false positives rates, depending on how allele frequencies, sample sizes, and phenotypic variances vary across the studies that are pooled. We develop a procedure to compute variant-specific inflation factors, and show how it can be used for diagnosis of genetic association analyses on pooled individual level data from multiple studies. We describe a WGS-appropriate analysis approach, implemented in freely-available software, which allows study-specific variances and thereby improves performance in practice. We illustrate the variance stratification problem, its solutions, and the proposed diagnostic procedure, in simulations and in data from the Trans-Omics for Precision Medicine Whole Genome Sequencing Program (TOPMed), used in association tests for hemoglobin concentrations and BMI.

PMID:34108454 | DOI:10.1038/s41467-021-23655-2

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Nevin Manimala Statistics

Age of red blood cells is not associated with in-hospital mortality in massively transfused patients

J Trauma Acute Care Surg. 2021 Apr 8. doi: 10.1097/TA.0000000000003192. Online ahead of print.

ABSTRACT

BACKGROUND: Studies comparing mortality following massive transfusion (MT) with fresher versus longer-stored red blood cells (RBCs) have focused on trauma patients. The Australian and New Zealand Massive Transfusion Registry (ANZMTR) collects data on all adult MT cases (≥5 RBCs within 4 hours, any bleeding context, ≥ 18 years) at participating hospitals.

METHODS: 2007-2018 data from 29 hospitals were analyzed to quantify the association between mortality and RBC storage time in adult MT cases. We ran three logistic regression models separately on each of seven bleeding contexts, with in-hospital mortality as the outcome and, in turn, (1) mean storage time (STmean) quartiles, (2) proportion of RBCs ≥30 days old (propOLD), and (3) scalar age of blood index (SBI) as predictors.

RESULTS: 8,685 adult MT cases involving transfusion of 126,622 RBCs were analyzed with Australian and New Zealand data analyzed separately. Mean storage times for these cases were (by quartile in ascending order) Australia: 12.5 days (range: 3.1-15.5 days), 17.7 (15.5-19.9), 22.3 (19.9-24.9), 29.8 (24.9-41.7); New Zealand: 11.3 (3.6-13.7), 15.3 (13.7-16.8), 18.7 (16.8-20.7), 24.5 (20.7-35.6). The odds ratios comparing in-hospital mortality for each quartile to that of the control first quartile (freshest blood), proportion of longer-stored (≥30 days) RBCs, and SBI were not statistically significant across all bleeding contexts.

CONCLUSIONS: We find no correlation between in-hospital mortality and storage time of transfused RBCs in a large cohort of adult MT patients representing all bleeding contexts. These results are consistent with those of recent large multi-center trials.

LEVEL OF EVIDENCE: Level III (retrospective study with one negative criterion [heterogeneous population]).

PMID:34108423 | DOI:10.1097/TA.0000000000003192

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Nevin Manimala Statistics

Effect of intraoperative methadone vs other opioids on postoperative outcomes: a meta-analysis of randomized controlled studies

Pain. 2021 Apr 5. doi: 10.1097/j.pain.0000000000002296. Online ahead of print.

ABSTRACT

Recent randomized controlled trials comparing the efficacy between intraoperative methadone and other opioids on postoperative outcomes have been limited by their small sample sizes and conflicting results. We performed a meta-analysis on randomized controlled trials which investigated outcomes between methadone and an opioid control group. Primary outcome data included postoperative opioid consumption, number of patients who received postoperative opioids, time to first analgesic, and pain scores. Secondary outcomes included time to extubation and incidence of nausea, vomiting, and respiratory depression. Statistical analysis was performed using RevMan. A P < 0.05 was considered statistically significant. Nine studies comprising 632 patients were included. There was no statistically significant reduction in opioid consumption postoperatively between the groups. Forty-seven percentage of patients in the methadone group received a dose of opioid postoperatively compared with 55% in the other opioids control group, which was not statistically significant. (P = 0.25) There was no difference in average time to receiving first postoperative analgesic among the groups. Pain scores within 24 hours were significantly lower in the methadone group when compared with other opioids (8 studies, n = 622, -0.49 [-0.74, -0.23], P = 0.002). However, there was no difference between 24 and 72 hours. There was no difference among the groups with respect to extubation time, nausea, vomiting, or respiratory depression. This meta-analysis concludes that there is currently insufficient evidence for the use of intraoperative methadone, when compared with other opioids. Although there was a decrease in average pain scores with methadone when compared with controls at 24 hours, there was no difference between 24 and 72 hours.

PMID:34108437 | DOI:10.1097/j.pain.0000000000002296

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Nevin Manimala Statistics

Heart Rate Variability and Pain Sensitivity in Chronic Low Back Pain Patients Exposed to Passive Viewing of Photographs of Daily Activities

Clin J Pain. 2021 Jun 9. doi: 10.1097/AJP.0000000000000953. Online ahead of print.

ABSTRACT

OBJECTIVES: We sought to investigate emotional reactivity by measuring HRV and pressure pain sensitivity during a passive visualization task in participants with chronic low back pain (CLBP).

METHODS: This case-control study was composed of 47 participants with CLBP and 47 asymptomatic participants. Both groups were submitted to a passive visualization task using 27 pictures from PHODA (Photograph Series of Daily Activities). HRV frequency domains were measured before, during, and after the task. Pressure pain threshold (PPT) and pain intensity were also measured before and after the task.

RESULTS: The adjusted mean difference was statistically significant for HRV frequency domains during the visualization task, including low frequency (-5.92; 95%CI=-9.60 to -2.23), high frequency (-0.71; 95%CI=-1.02 to -0.39), and low frequency/high frequency ratio (8.82; 95%CI=5.19 to 12.45). PPT decreased after the task in the low back pain group in all body sites, and pain intensity increased (-0.8; 95% CI=-1.16 to -0.39).

DISCUSSION: Aversive environmental stimuli, such as visual cues, may generate defensive physiological reactions. Heart rate variability (HRV) can provide an available measure that reflects the perceptions of threat and safety in the environment. Participants with chronic low back pain presented changes in sympathovagal balance during passive visualization of pictures of daily activities, higher pain sensitivity, and high pain intensity when they are exposed to a passive visualization task using pictures of daily living that may arouse fears of harm.

PMID:34108363 | DOI:10.1097/AJP.0000000000000953

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Nevin Manimala Statistics

Long-Term Outcomes of a Community of Practice for Dietitians Working in Aboriginal and Torres Strait Islander Health: A Multimethod, Follow-up Study

J Contin Educ Health Prof. 2021 Jun 8. doi: 10.1097/CEH.0000000000000370. Online ahead of print.

ABSTRACT

INTRODUCTION: Dietitians are in an important position to work alongside Aboriginal and Torres Strait Islander peoples to improve their health and may play a role in reducing the burden of disease experienced by Aboriginal and Torres Strait Islander peoples. Many dietitians do not feel confident to practice effectively in these settings and require improved workforce development opportunities. Communities of Practice can improve dietitians’ confidence and practice in Aboriginal and Torres Strait Islander health; however, evidence for long-term impacts is limited. This study aims to determine if a Community of Practice can have long-term impacts on dietitians working in Aboriginal and Torres Strait Islander health.

METHODS: Data were collected through semistructured interviews and a cultural awareness self-assessment tool. Analysis was through a multimethod approach and combined qualitative inductive thematic analysis, social network analysis, and descriptive statistics.

RESULTS: Three main areas of long-term impact were identified including development of a social and professional network, career progression and retention, and a fundamental change in thinking and practice. All participants experienced feelings of support and increased confidence.

DISCUSSION: Communities of practice may be a feasible, low-cost workforce development strategy that can reduce dietitians’ feelings of professional isolation when working in Aboriginal and Torres Strait Islander health. Further research is required to identify the mechanisms underlying sustained impacts. Social network analysis, combined with realist evaluation may be an appropriate research design, to answer future and more in-depth questions about the effectiveness of communities of practice.

PMID:34108390 | DOI:10.1097/CEH.0000000000000370

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Does Women’s Screening History Have Any Impact on Mammography Screening Attendance After Tailored Education?: A Systematic Review and Meta-analysis

Med Care. 2021 Jun 9. doi: 10.1097/MLR.0000000000001576. Online ahead of print.

ABSTRACT

BACKGROUND: Many ethnic minority women have low attendance at breast cancer screening.

OBJECTIVES: This brief report explores whether women’s screening histories impact mammography screening attendance after tailored education.

RESEARCH DESIGN: Systematic searches were conducted in 5 databases. Randomized controlled trials of educational interventions tailored to ethnic minority women that measured attendance at mammography screening were eligible for inclusion. Data extraction and risk of bias assessment were performed independently. Data were combined in a meta-analysis by using random effects models. Heterogeneity was estimated by using I2 statistics.

RESULTS: Six studies with 3521 women were eligible for inclusion. The D+L pooled risk ratio (RR) for mammography attendance for never screened participants was 1.54 (95% confidence interval, 1.24-1.91; P<0.001), with low heterogeneity (I2=27.1%, P=0.231). The D+L pooled risk ratio for attendance for ever screened participants was 1.26 (95% confidence interval, 1.11-1.43; P<0.001), with low heterogeneity (I2=35.5%, P=0.213).

CONCLUSIONS: Tailored education increased attendance at mammography by 54% among never screened women and 26% among ever screened women. Although these findings must be interpreted with caution, the findings suggest that women’s screening history is an important and ignored variable that affects how effective tailored education is on mammography screening attendance.

PMID:34108408 | DOI:10.1097/MLR.0000000000001576

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Nevin Manimala Statistics

The effect of resin cement shade and restorative material type and thickness on the final color of resin-matrix ceramics

J Prosthodont Res. 2021 Jun 10. doi: 10.2186/jpr.JPR_D_20_00138. Online ahead of print.

ABSTRACT

PURPOSE: This study aims to evaluate the effects of cement shade, restorative material type, and thickness on the final color of resin-matrix ceramics.

METHODS: Ninety A2 shade resin-matrix ceramic specimens were prepared from Vita Enamic, GC Cerasmart, and Lava Ultimate at 0.5 and 1.0 mm thicknesses. Sixty resin cement disks were fabricated from different shades (A1, A3O, B05, and TR) of RelyX Ultimate at 0.1 mm thickness. CIE color coordinates were measured using a spectrophotometer, and color differences (∆ E 00 ) were calculated. Data were statistically analyzed (P =0.05).

RESULTS: The ΔE 00 values were influenced by the cement shade, restorative material type, thickness, and their interactions ( P < 0.05). A3O cement caused clinically unacceptable values for all groups at 0.5 mm thickness and GC at 1.0 mm thickness. A1 and TR cement shades demonstrated visually perceptible but clinically acceptable values, except for VE-A1 and LU-A1 at 0.5 mm thickness. The ∆E 00 values of the B05 cement shade were lower than the visually perceptible threshold for both thicknesses except for GC at 0.5 mm thickness.

CONCLUSIONS: The shade of the resin cement and the type and thickness of the resin-matrix ceramic material significantly affected the resulting final color. To provide a shade matching with natural dentition and to obtain esthetic restorations, especially for the anterior teeth, the resin cement shade and resin-matrix ceramic material should be carefully selected.

PMID:34108295 | DOI:10.2186/jpr.JPR_D_20_00138

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Nevin Manimala Statistics

Fatigue failure and success rate of lithium disilicate table-tops as a function of cement thickness

J Prosthodont Res. 2021 Jun 10. doi: 10.2186/jpr.JPR_D_20_00220. Online ahead of print.

ABSTRACT

PURPOSE: Under thin, partial coverage restoration the proper cement thickness to be clinically employed still remains an issue. The aim of this study was to determine the failure and success rates of simplified lithium disilicate occlusal veneers as a function of cement thickness. The null hypothesis was that cement thickness has no effect on the fatigue resistance.

METHODS: Sound human molars were severed in a plane parallel to the occlusal surface to create a flat dentin surface surrounded by enamel edges. Forty-five occlusal veneers 1.0 mm thick (IPS e.max CAD LT) were luted to the teeth with Multilink Automix resin cement, creating 3 experimental groups (n=15) with cement thicknesses of 50, 100, and 200 µm. The restorations were fatigue-cycled using a ball mill machine containing zirconia and stainless steel spheres. Twelve 60 min cycles were performed. Survival statistics were applied to “failure” and “success” events, comparing the three groups using a log-rank Mantel-Cox test and a log-rank test for trends (alpha = 0.05).

RESULTS: The failure and success rates were not significantly influenced by cement thickness (P = 0.137 and P = 0.872, respectively); thus, the null hypothesis was accepted. However, when log-rank test for trends was applied to failure events, the tendency to have less failures with increasing thicknesses was found statistically significant (P = 0.047).

CONCLUSIONS: The cement thickness within the range adopted here did not have a significant effect on the failure or success rate of lithium disilicate occlusal veneers when exposed to randomized impact stresses generating fatigue phenomena.

PMID:34108297 | DOI:10.2186/jpr.JPR_D_20_00220

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Fracture resistance of maxillary premolars restored with different endocrown designs and materials after artificial ageing

J Prosthodont Res. 2021 Jun 10. doi: 10.2186/jpr.JPR_D_20_00082. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the effect of three different designs and two monolithic ceramic materials on the durability and fracture resistance of endocrowns on maxillary first premolars, in comparison to post-and-core crowns.

METHODS: Fifty-six maxillary premolars were endodontically treated and shortened to a level of 2 mm from the cervical line, and randomly categorized into six endocrown groups and post-and-core crown control group (n=8); E1; endocrowns with flat occlusal table (without ferrule), E2; endocrowns with 1.5 mm circumferential ferrule, E3; endocrowns with 1.5 mm buccal ferrule preparation. Two materials were used for endocrowns: zirconia (4YSZ; Z), and lithium disilicate (L). The control group was restored with zirconia posts, and lithium disilicate crowns. All restorations were bonded using Panavia V5 and its respective primers and underwent thermo-mechanical fatigue with a 10 kg dynamic load for 1,200,000 cycles and thermocycling between 5 and 55 °C. Thereafter all survived specimens were loaded to fracture. The results were statistically analyzed using ANOVA and T-Test.

RESULTS: None of the specimens showed any signs of debonding or fracture caused by the fatigue test. The PC control group showed no statistically significant difference in comparison to groups ZE1, ZE2 and LE2 ( p > 0.05 ). However, it was significantly different from groups LE1, LE3, and ZE3 ( p ≤ 0.05 ).

CONCLUSIONS: Preparation designs and materials affected the fracture resistance of endocrowns. The results showed a superiority of the post-and-core crowns,zirconia/lithium disilicate endocrowns with 1.5 mm circumferential ferrule, and zirconia endocrowns with the flat occlusal table.

PMID:34108294 | DOI:10.2186/jpr.JPR_D_20_00082

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Nevin Manimala Statistics

A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression

Sci Transl Med. 2021 Jun 9;13(597):eabe1376. doi: 10.1126/scitranslmed.abe1376.

ABSTRACT

Nitrous oxide at 50% inhaled concentration has been shown to improve depressive symptoms in patients with treatment-resistant major depression (TRMD). Whether a lower concentration of 25% nitrous oxide provides similar efficacy and persistence of antidepressant effects while reducing the risk of adverse side effects is unknown. In this phase 2 clinical trial (NCT03283670), 24 patients with severe TRMD were randomly assigned in a crossover fashion to three treatments consisting of a single 1-hour inhalation with (i) 50% nitrous oxide, (ii) 25% nitrous oxide, or (iii) placebo (air/oxygen). The primary outcome was the change on the Hamilton Depression Rating Scale (HDRS-21). Whereas nitrous oxide significantly improved depressive symptoms versus placebo (P = 0.01), there was no difference between 25 and 50% nitrous oxide (P = 0.58). The estimated differences between 25% and placebo were -0.75 points on the HDRS-21 at 2 hours (P = 0.73), -1.41 points at 24 hours (P = 0.52), -4.35 points at week 1 (P = 0.05), and -5.19 points at week 2 (P = 0.02), and the estimated differences between 50% and placebo were -0.87 points at 2 hours (P = 0.69), -1.93 points at 24 hours (P = 0.37), -2.44 points at week 1 (P = 0.25), and -7.00 points at week 2 (P = 0.001). Adverse events declined substantially with dose (P < 0.001). These results suggest that 25% nitrous oxide has comparable efficacy to 50% nitrous oxide in improving TRMD but with a markedly lower rate of adverse effects.

PMID:34108247 | DOI:10.1126/scitranslmed.abe1376