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Nevin Manimala Statistics

A Bayesian mixture model for changepoint estimation using ordinal predictors

Int J Biostat. 2021 Apr 6. doi: 10.1515/ijb-2020-0151. Online ahead of print.

ABSTRACT

In regression models, predictor variables with inherent ordering, such ECOG performance status or novel biomarker expression levels, are commonly seen in medical settings. Statistically, it may be difficult to determine the functional form of an ordinal predictor variable. Often, such a variable is dichotomized based on whether it is above or below a certain cutoff. Other methods conveniently treat the ordinal predictor as a continuous variable and assume a linear relationship with the outcome. However, arbitrarily choosing a method may lead to inaccurate inference and treatment. In this paper, we propose a Bayesian mixture model to consider both dichotomous and linear forms for the variable. This allows for simultaneous assessment of the appropriate form of the predictor in regression models by considering the presence of a changepoint through the lens of a threshold detection problem. This method is applicable to continuous, binary, and survival outcomes, and it is easily amenable to penalized regression. We evaluated the proposed method using simulation studies and apply it to two real datasets. We provide JAGS code for easy implementation.

PMID:33823087 | DOI:10.1515/ijb-2020-0151

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Nevin Manimala Statistics

Validation of a continuous measure of cardiometabolic risk among adolescents

J Pediatr Endocrinol Metab. 2021 Apr 7. doi: 10.1515/jpem-2020-0600. Online ahead of print.

ABSTRACT

OBJECTIVES: We validated a continuous cardiometabolic risk (CMR) measure among adolescents.

METHODS: Five metabolic syndrome (MetS) components including waist circumference, triglycerides, high-density lipoprotein cholesterol, fasting blood glucose, and mean arterial pressure were assessed in a national cohort of U.S. adolescents (n=560; 16.5 ± 0.5 y/o at baseline) in 10th grade (2010, Wave 1 (W1)), and follow-up assessments four (W4) and seven (W7) years later. Separately by wave, linear regressions were fitted to each MetS component controlling for age, sex, and race/ethnicity, and yielded standardized residuals (Z-scores). Wave-specific component Z-scores were summed to obtain composite CMR Z-scores. Four- and seven-year CMR change (CMR-diff W1-W4 and W1-W7). and average CMR risk (CMR-avg; (W1 + W4)/2 and (W1 + W7)/2) were calculated using the CMR Z-scores. W7 MetS was determined using adult criteria. Student’s t-test and receiver operating characteristic (ROC) curve were conducted.

RESULTS: Participants meeting the adult criteria for MetS at W7 (74 of 416, 17.8%) had statistically significant (p<0.01) higher values for W1 CMR Z-scores (0.92 vs. -0.21), W4 CMR Z-scores (1.69 vs. -0.28), W7 CMR Z-scores (2.21 vs. -0.55), W1-W4 CMR-avg (1.53 vs. -0.27), W1-W7 CMR-diff (1.29 vs. -0.21), and W1-W7 CMR-avg (1.46 vs. -0.48) than those not meeting MetS criteria. Most results were similar for males and females in the sex-stratified analyses. The areas under the ROC curve were 0.61, 0.71, and 0.75 for W1, W4 and W7 Z-scores.

CONCLUSIONS: Findings support the validity of the continuous CMR Z-scores calculated using linear regression in evaluating and monitoring CMR profiles from adolescence to early adulthood.

PMID:33823099 | DOI:10.1515/jpem-2020-0600

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Nevin Manimala Statistics

Using Treatment Fidelity Measures to Understand Walking Recovery: A Secondary Analysis from the Community Ambulation Project

Phys Ther. 2021 Apr 5:pzab109. doi: 10.1093/ptj/pzab109. Online ahead of print.

ABSTRACT

OBJECTIVES: Physical therapy intervention studies can be deemed ineffective when, in fact, they may not have been delivered as intended. Measurement of treatment fidelity (TF) can address this issue. The purpose was to describe TF of a home-based intervention, identify factors associated with TF, and examine whether components of TF were associated with the outcome of change in 6-minute walk distance (∆6MWD).

METHODS: This is a secondary analysis of community-dwelling hip fracture participants who completed standard therapy and were randomized to the active intervention (Push). Push was 16-weeks of lower extremity strengthening, function and endurance training. TF was defined as delivery (attendance rate, exercise duration) and receipt (progression in training load, heart rate reserve (HRR) during endurance training, and exercise position (exercise on floor). The outcome was ∆6MWD. Independent variables included baseline (demographic and clinical) measures. Descriptive statistics were calculated; linear and logistic regressions were performed.

RESULTS: 89 participants were included in this analysis; 59 (66%) had attendance ≥75%. Participants walked for ≥20 minutes for 78% of sessions. The average training load increased by 22%; the mean HRR was 35%; and 61 (69%) participants exercised on the floor ≥75% of sessions. Regression analyses showed that a higher body mass index (BMI) and greater baseline 6MWD were related to components of TF; and four out of 5 components of TF were significantly related to ∆6MWD. The strongest TF relationship showed that those who exercised on the floor improved by 62 meters (95% CI: 31, 93) more than those who did not get on the floor.

CONCLUSIONS: Measures of TF should extend beyond attendance rate. This analysis demonstrates how measures of TF, including program attendance, progression in training load, endurance duration and exercising on the floor were significantly related to improvement in 6MWD in participants post hip fracture.

IMPACT: This careful analysis of treatment fidelity assured that the intervention was delivered and received as intended. Analysis of data from a large trial with participants after hip fracture showed that regular attendance, frequent endurance training for 20 minutes, increases in lower extremity training loads, and exercising on the floor were associated with improvements in the outcome of 6-minute-walk distance. The strongest association with improvement was exercising on the floor.

PMID:33823028 | DOI:10.1093/ptj/pzab109

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Nevin Manimala Statistics

Assessing reinforcing versus aversive consequences in a real-time secondhand smoke intervention

Transl Behav Med. 2021 Apr 5:ibab004. doi: 10.1093/tbm/ibab004. Online ahead of print.

ABSTRACT

Few studies have examined the relative effectiveness of reinforcing versus aversive consequences at changing behavior in real-world environments. Real-time sensing devices makes it easier to investigate such questions, offering the potential to improve both intervention outcomes and theory. This research aims to describe the development of a real-time, operant theory-based secondhand smoke (SHS) intervention and compare the efficacy of aversive versus aversive plus reinforcement contingency systems. Indoor air particle monitors were placed in the households of 253 smokers for approximately three months. Participants were assigned to a measurement-only control group (N = 129) or one of the following groups: 1.) aversive only (AO, N = 71), with aversive audio/visual consequences triggered by the detection of elevated air particle measurements, or 2.) aversive plus reinforcement (AP, N = 53), with reinforcing consequences contingent on the absence of SHS added to the AO intervention. Residualized change ANCOVA analysis compared particle concentrations over time and across groups. Post-hoc pairwise comparisons were also performed. After controlling for Baseline, Post-Baseline daily particle counts (F = 6.42, p = 0.002), % of time >15,000 counts (F = 7.72, p < 0.001), and daily particle events (F = 4.04, p = 0.02) significantly differed by study group. Nearly all control versus AO/AP pair-wise comparisons were statistically significant. No significant differences were found for AO versus AP groups. The aversive feedback system reduced SHS, but adding reinforcing consequences did not further improve outcomes. The complexity of real-world environments requires the nuances of these two contingency systems continue to be explored, with this study demonstrating that real-time sensing technology can serve as a platform for such research.

PMID:33823045 | DOI:10.1093/tbm/ibab004

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Nevin Manimala Statistics

Occupational exposures and risk of nasopharyngeal carcinoma in a high-risk area: A population-based case-control study

Cancer. 2021 Apr 6. doi: 10.1002/cncr.33536. Online ahead of print.

ABSTRACT

BACKGROUND: The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas.

METHODS: The authors conducted a population-based case-control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self-reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration-response relations.

RESULTS: Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26-1.68), chemical vapors (OR, 1.37; 95% CI, 1.17-1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25-1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30-1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia.

CONCLUSIONS: Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas.

LAY SUMMARY: The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC. Duration-response trends were observed with increasing duration of exposure. These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high-incidence region.

PMID:33823062 | DOI:10.1002/cncr.33536

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Nevin Manimala Statistics

Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer

J Radiat Res. 2021 Apr 5:rraa056. doi: 10.1093/jrr/rraa056. Online ahead of print.

ABSTRACT

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions.

PMID:33822986 | DOI:10.1093/jrr/rraa056

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Nevin Manimala Statistics

Body Mass Index and Risk of Second Cancer among Women with Breast Cancer

J Natl Cancer Inst. 2021 Apr 5:djab053. doi: 10.1093/jnci/djab053. Online ahead of print.

ABSTRACT

BACKGROUND: Breast cancer survivors are at increased risk for developing second primary cancers compared to the general population. Little is known about whether body mass index (BMI) increases this risk. We examined the association between BMI and second cancers among women with incident invasive breast cancer.

METHODS: This retrospective cohort included 6,481 patients from Kaiser Permanente Colorado and Washington of whom 822 (12.7%) developed a second cancer (mean follow-up was 88.0 months). BMI at the first cancer was extracted from the medical record. Outcomes included: 1) all second cancers, 2) obesity-related second cancers, 3) any second breast cancer, and 4) estrogen receptor (ER)-positive second breast cancers. Multivariable Poisson regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI) for second cancers associated with BMI adjusted for site, diagnosis year, treatment, demographic, and tumor characteristics.

RESULTS: The mean age at initial breast cancer diagnosis was 61.2 (standard deviation = 11.8) years. Most cases were overweight (33.4%) or obese (33.8%) and diagnosed at stage I (62.0%). In multivariable models, for every 5 kg/m2 increase in BMI, the risk of any second cancer diagnosis increased by 7% (RR = 1.07, 95% CI = 1.01 to 1.14); 13% (RR = 1.13, 95% CI = 1.05 to 1.21) for obesity-related cancers; 11% (RR = 1.11, 95% CI = 1.02 to 1.21) for a second breast cancer, and 15% (RR = 1.15, 95% CI = 1.04 to 1.27) for a second ER-positive breast cancer.

CONCLUSION: We observed a statistically significant increased risk of second cancers associated with increasing BMI. These findings have important public health implications given the prevalence of overweight and obesity in breast cancer survivors and underscore the need for effective prevention strategies.

PMID:33823007 | DOI:10.1093/jnci/djab053

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Nevin Manimala Statistics

Are resistance rates among bloodstream isolates a good proxy for other infections? Analysis from the BSAC Resistance Surveillance Programme

J Antimicrob Chemother. 2021 Apr 5:dkab096. doi: 10.1093/jac/dkab096. Online ahead of print.

ABSTRACT

BACKGROUND: Bacteraemia data are often used as a general measure of resistance prevalence but may poorly represent other infection types. We compared resistance prevalence between bloodstream infection (BSI) and lower respiratory tract infection (LRTI) isolates collected by the BSAC Resistance Surveillance Programme.

METHODS: BSI isolates (n = 8912) were collected during 2014-18 inclusive and LRTI isolates (n = 6280) between October 2013 to September 2018 from participating laboratories in the UK and Ireland, to a fixed annual quota per species group. LRTI isolates, but not BSI, were selected by onset: community for Streptococcus pneumoniae; hospital for Staphylococcus aureus, Pseudomonas aeruginosa and Enterobacterales. MICs were determined centrally by agar dilution; statistical modelling adjusted for ICU location and possible clustering by collection centre.

RESULTS: Resistance was more prevalent among the LRTI isolates, even after adjusting for a larger proportion of ICU patients. LRTI P. aeruginosa and S. pneumoniae were more often resistant than BSI isolates for most antibiotics, and the proportion of MRSA was higher in LRTI. For S. pneumoniae, the observation reflected different serotype distributions in LRTI and BSI. Relationships between LRTI and resistance were less marked for Enterobacterales, but LRTI E. coli were more often resistant to β-lactams, particularly penicillin/β-lactamase inhibitor combinations, and LRTI K. pneumoniae to piperacillin/tazobactam. For E. cloacae there was a weak association between LRTI, production of AmpC enzymes and cephalosporin resistance.

CONCLUSIONS: Estimates of resistance prevalence based upon bloodstream isolates underestimate the extent of the problem in respiratory isolates, particularly for P. aeruginosa, S. pneumoniae, S. aureus and, less so, for Enterobacterales.

PMID:33822968 | DOI:10.1093/jac/dkab096

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Nevin Manimala Statistics

Proximal aortic aneurysms: correlation of maximum aortic diameter and aortic wall thickness

Eur J Cardiothorac Surg. 2021 Apr 5:ezab147. doi: 10.1093/ejcts/ezab147. Online ahead of print.

ABSTRACT

OBJECTIVES: The goal of therapy of proximal aortic aneurysms is to prevent an aortic catastrophe, e.g. acute dissection or rupture. The decision to intervene is currently based on maximum aortic diameter complemented by known risk factors like bicuspid aortic valve, positive family history or rapid growth rate. When applying Laplace’s law, wall tension is determined by pressure × radius divided by aortic wall thickness. Because current imaging modalities lack precision, wall thickness is currently neglected. The purpose of our study was therefore to correlate maximum aortic diameter with aortic wall thickness and known indices for adverse aortic events.

METHODS: Aortic samples from 292 patients were collected during cardiac surgery, of whom 158 presented with a bicuspid aortic valve and 134, with a tricuspid aortic valve. Aortic specimens were obtained during the operation and stored in 4% formaldehyde. Histological staining and analysis were performed to determine the thickness of the aortic wall.

RESULTS: Patients were 62 ± 13 years old at the time of the operation; 77% were men. The mean aortic dimensions were 44 mm, 41 mm and 51 mm at the aortic root, sinotubular junction and ascending aorta, respectively. Aortic valve stenosis was the most frequent (49%) valvular dysfunction, followed by aortic valve regurgitation (33%) and combined dysfunction (10%). The maximum aortic diameter at the ascending level did not correlate with the thickness of the media (R = 0.07) or the intima (R = 0.28) at the convex sample site. There was also no correlation of the ascending aortic diameter with age (R = -0.18) or body surface area (R = 0.07). The thickness of the intima (r = 0.31) and the media (R = 0.035) did not correlate with the Svensson index of aortic risk. Similarly, there was a low (R = 0.29) or absent (R = -0.04) correlation between the aortic size index and the intima or media thickness, respectively. There was a similar relationship of median thickness of the intima in the 4 aortic height index risk categories (P < 0.001).

CONCLUSIONS: Aortic diameter and conventional indices of aortic risk do not correlate with aortic wall thickness. Other indices may be required in order to identify patients at high risk for aortic complications.

PMID:33822923 | DOI:10.1093/ejcts/ezab147

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Nevin Manimala Statistics

Monitoring of Three-Phase Variations in the Mortality of Covid-19 Pandemic Using Control Charts: Where Does Pakistan Stand?

Int J Qual Health Care. 2021 Apr 5:mzab062. doi: 10.1093/intqhc/mzab062. Online ahead of print.

ABSTRACT

BACKGROUND: At the end of December 2019, the world in general and Wuhan, the industrial hub of China, in particular, experienced the COVID-19 pandemic. Massive increment of cases and deaths occurred in China and 209 countries in Europe, America, Australia, Asia, and Pakistan. Pakistan was first hit by COVID-19 when a case was reported in Karachi on 26 February 2020. Several methods were presented to model the death rate due to the COVID-19 pandemic and to forecast the pinnacle of reported deaths. Still, these methods were not used in identifying the first day when Pakistan enters or exits the early exponential growth phase.

METHODS: New approaches are needed that display the death patterns and signal an alarming situation so that corrective actions can be taken before the condition worsens. To meet this purpose, secondary data on daily reported deaths due to the COVID-19 pandemic have been considered, and the c and exponentially weighted moving average (EWMA) control charts are used to monitor variations in deaths and to identify the growth phases such as pre-growth, growth, and post-growth phases in Pakistan due to the COVID-19 pandemic.

RESULTS: The-chart shows that Pakistan switches from the pre-growth to the growth phase on 31 March 2020. The EWMA chart demonstrates that Pakistan remains in the growth-phase from 31 March 2020 to 17 August 2020, with some indications signaling a decrease in deaths. It is found that Pakistan moved to a post-growth phase for a brief period from 27 July 2020 to 28 July 2020. The country encounters a re-growth phase right after this short-term post-growth phase, but the number of deaths is decreasing in that Pakistan may approach the post-growth phase shortly.

CONCLUSION: This novel amalgamation of control charts illustrates a systematic implementation of the charts to government leaders and forefront medical teams to facilitate the rapid detection of daily reported deaths due to COVID-19. Besides government and public health officials, it is also the public’s responsibility to follow the enforced standard operating procedures as a temporary remedy of this pandemic in ensuring public safety while awaiting a suitable vaccine to be discovered.

PMID:33822932 | DOI:10.1093/intqhc/mzab062