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Nevin Manimala Statistics

Special Collection: Celebrating J.D. Murray’s Contributions to Mathematical Biology

Bull Math Biol. 2021 Dec 4;84(1):13. doi: 10.1007/s11538-021-00955-8.

NO ABSTRACT

PMID:34865189 | DOI:10.1007/s11538-021-00955-8

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Nevin Manimala Statistics

Reliability and validity of expert assessments of hand-wrist physical exposures

Am J Ind Med. 2021 Dec 5. doi: 10.1002/ajim.23318. Online ahead of print.

ABSTRACT

BACKGROUND: General population job-exposure matrices (JEMs) based on expert assessments of physical exposures may be valuable tools for studying occupation-related musculoskeletal disorders. Wrist-hand JEMs are few and the reliability and validity of expert assessments of wrist-hand exposures is uncertain.

METHODS: We examined intra- and inter-rater reliability of ratings of five experts of hand-wrist repetition, deviation, force, vibration, and computer work in 33 jobs selected to represent a large exposure variation. The validity of ratings of hand-wrist repetition was examined by comparison with electro-goniometer measurements of wrist angular velocity and mean power frequency (MPF), and the validity of hand-wrist deviation by comparison with goniometer measurements of range of motion (ROM).

RESULTS: Intra-rater test-retest and inter-rater Spearman correlation coefficients controlling for rater effects, varied between 0.70 and 0.87. Corresponding kappa statistics of overall agreement showed similar high values, except for wrist deviation (kappa = 0.50). Regression analyses showed strong positive associations between expert assessments of repetition and goniometer measurements of wrist angular velocity (R2 = 0.56, p < 0.0001) and MPF (R2 = 0.37, p < 0.0003), while expert ratings of wrist deviation showed a weak statistically nonsignificant association with goniometer measurements of ROM (R2 = 0.032, p = 0.34).

CONCLUSION: The reliability of expert assessments of wrist-hand physical exposures was high. Compared to goniometer measurements, the validity of assessments of wrist-hand repetition was also high, but it was low for assessments of wrist-hand deviation. The results are encouraging for establishing a hand-wrist JEM, but the results for wrist deviation emphasize that expert assessments should be validated against objective measurements.

PMID:34865239 | DOI:10.1002/ajim.23318

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Nevin Manimala Statistics

Resident physicians physical activity during on-call shifts: smartphone-based assessment

Occup Med (Lond). 2021 Dec 2:kqab159. doi: 10.1093/occmed/kqab159. Online ahead of print.

ABSTRACT

BACKGROUND: Physical activity of resident physicians (RPs) during on-call shifts is difficult to objectively evaluate. The integration of smartphones in our daily routines may allow quantitative assessment, employing pedometric assessment.

AIMS: To evaluate the number of steps that RPs walk during on-call shifts as a marker of physical activity by using smartphone-based pedometers.

METHODS: Step counts were collected from 100 RPs’ smartphones who volunteered to participate in the study between January 2018 and May 2019. The conversion rate was 1400 steps = 1 km (application’s default). A shift was defined as regular morning work followed by an in-house on-call stay, totalling 26 hours. Statistical analyses included univariate and multivariate linear mixed models, and Fisher exact test. A P-value < 0.05 was considered statistically significant.

RESULTS: The average walking distance was 12 118 steps (8.6 km/RP/shift). Paediatric intensive care unit and neurosurgery residents recorded the longest walking distances 16 347 and 15 630 steps (11.67 and 11.16 km/shift), respectively. Radiology residents walked the shortest distances 4718 steps (3.37 km/shift). Physically active RPs walked significantly longer distances during their shifts than non-physically active RPs: 12 527 steps versus 11 384 steps (8.95 versus 8.13 km/shift, P < 0.05), respectively. Distances covered during weekday shifts were longer than weekend shifts: 12 092 steps versus 11 570 steps (8.63 versus 8.26 km/shift, P < 0.05), respectively.

CONCLUSIONS: Smartphone-based pedometers can aid in analysing physical activity and workload during on-call shifts; such information can be valuable for human resource department, occupational health authorities and medical students with impaired physical mobility when choosing a speciality.

PMID:34865160 | DOI:10.1093/occmed/kqab159

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Nevin Manimala Statistics

Accuracy of pulse pressure variations for fluid responsiveness prediction in mechanically ventilated patients with biphasic positive airway pressure mode

J Clin Monit Comput. 2021 Dec 5. doi: 10.1007/s10877-021-00789-8. Online ahead of print.

ABSTRACT

The accuracy of pulse pressure variation (PPV) to predict fluid responsiveness using pressure-controlled (PC) instead of volume-controlled modes is under debate. To specifically address this issue, we designed a study to evaluate the accuracy of PPV to predict fluid responsiveness in severe septic patients who were mechanically ventilated with biphasic positive airway pressure (BIPAP) PC-ventilation mode. 45 patients with sepsis or septic shock and who were mechanically ventilated with BIPAP mode and a target tidal volume of 7-8 ml/kg were included. PPV was automatically assessed at baseline and after a standard fluid challenge (Ringer’s lactate 500 ml). A 15% increase in stroke volume (SV) defined fluid responsiveness. The predictive value of PPV was evaluated through a receiver operating characteristic (ROC) curve analysis and “gray zone” statistical approach. 20 (44%) patients were considered fluid responders. We identified a significant relationship between PPV decrease after volume expansion and SV increase (spearman ρ = – 0.5, p < 0.001). The area under ROC curve for PPV was 0.71 (95%CI 0.56-0.87, p = 0.007). The best cut-off (based on Youden’s index) was 8%, with a sensitivity of 80% and specificity of 60%. Using a gray zone approach, we identified that PPV values comprised between 5 and 15% do not allow a reliable fluid responsiveness prediction. In critically ill septic patients ventilated under BIPAP mode, PPV appears to be an accurate method for fluid responsiveness prediction. However, PPV values comprised between 5 and 15% constitute a gray zone that does not allow a reliable fluid responsiveness prediction.

PMID:34865181 | DOI:10.1007/s10877-021-00789-8

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Nevin Manimala Statistics

Analyzing Disparity and Rates of Morphological Evolution with Model-Based Phylogenetic Comparative Methods

Syst Biol. 2021 Dec 2:syab079. doi: 10.1093/sysbio/syab079. Online ahead of print.

ABSTRACT

Understanding variation in rates of evolution and morphological disparity is a goal of macroevolutionary research. In a phylogenetic comparative methods framework, we present three explicit models for linking the rate of evolution of a trait to the state of another evolving trait. This allows testing hypotheses about causal influences on rates of phenotypic evolution with phylogenetic comparative data. We develop a statistical framework for fitting the models with generalized least-squares regression and use this to discuss issues and limitations in the study of rates of evolution more generally. We show that the power to detect effects on rates of evolution is low in that even strong causal effects are unlikely to explain more than a few percent of observed variance in disparity. We illustrate the models and issues by testing if rates of beak-shape evolution in birds are influenced by brain size, as may be predicted from a Baldwin effect in which presumptively more behaviorally flexible large-brained species generate more novel selection on themselves leading to higher rates of evolution. From an analysis of morphometric data for 645 species, we find evidence that both macro- and microevolution of the beak are faster in birds with larger brains, but with the caveat that there are no consistent effects of relative brain size.[Baldwin effect; beak shape; behavioral drive; bird; brain size; disparity; phylogenetic comparative method; rate of evolution.].

PMID:34865153 | DOI:10.1093/sysbio/syab079

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Nevin Manimala Statistics

Effect of anti-angiotensin II type-1 receptor antibodies on the outcomes of kidney transplantation: a systematic review and meta-analysis

Nephrol Dial Transplant. 2021 Dec 3:gfab344. doi: 10.1093/ndt/gfab344. Online ahead of print.

ABSTRACT

BACKGROUND: Anti-angiotensin II type 1 receptor antibodies (AT1R-Abs) have been recognized as non-HLA antibodies associated with allograft rejection and poor allograft outcomes after kidney transplantation. The aim of this study was to assess the risk anti-AT1R-Abs pose for rejection and graft loss among kidney transplant populations.

METHODS: We systematically searched PubMed, EMBASE, and the Cochrane Library databases for relevant articles published from inception until June 2021 to identify all studies concerning the role AT1R-Abs play in the clinical outcome after kidney transplantation. Two reviewers independently identified studies, abstracted outcome data, and assessed the quality of the studies. The meta-analysis was summarized using the fixed-effects models or random-effects models, according to heterogeneity. The major outcomes included delayed graft function, acute rejection, graft loss, or patient death after transplantation.

RESULTS: Twenty-one eligible studies involving a total of 4,023 kidney transplantation recipients were included in the evaluation to identified. Meta-analysis results showed that the AT1R-Ab positive kidney transplant (KT) group had a greater incidence of antibody-mediated rejection (RR = 1.94, 95%CI: 1.61-2.33, P < 0.00001) and graft loss (RR = 2.37, 95%CI: 1.50-3.75, P = 0.0002) than did the AT1R-Abs negative KT group. There was no significant statistical difference in delayed graft function rate, T-cell mediated rejection, mixed rejection, acute cellular rejection, acute rejection, and patient death rate between AT1R-Ab positive KT and AT1R-Ab negative KT groups.

CONCLUSIONS: Our study shows that the presence of anti-AT1R-Abs was associated with a significantly higher risk of antibody-mediated rejection and graft loss in kidney transplantation. Future studies are still needed to evaluate the importance of routine anti-AT1R monitoring and therapeutic targeting. These results shows that assessment of anti-AT1R-Abs would be helpful in determining immunologic risk and susceptibility to immunologic events for recipients.

PMID:34865146 | DOI:10.1093/ndt/gfab344

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Nevin Manimala Statistics

Development and external validation of a diagnostic model for biopsy-proven acute interstitial nephritis using electronic health record data

Nephrol Dial Transplant. 2021 Dec 4:gfab346. doi: 10.1093/ndt/gfab346. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with acute interstitial nephritis (AIN) can present without typical clinical features, leading to a delay in diagnosis and treatment. We therefore developed and validated a diagnostic model to identify patients at risk of AIN using variables from the electronic health record.

METHODS: In patients who underwent a kidney biopsy at Yale between 2013-2018, we tested the association of over 150 variables with AIN including demographics, comorbidities, vital signs, and laboratory tests (training set, 70%). We used least absolute shrinkage and selection operator (LASSO) methodology to select pre-biopsy features associated with AIN. We performed AUC analysis with internal (held-out test set, 30%) and external validation (Biopsy Biobank Cohort of Indiana). We tested change in model performance after addition of urine biomarkers in Yale AIN study.

RESULTS: We included 393 patients (AIN = 22%) in training set, 158(AIN = 27%) in test set, 1118(AIN = 11%) in validation set, and 265(AIN = 11%) in Yale AIN study. Variables in selected model included serum creatinine (adjusted odds ratio, 2.31(1.42-3.76)), blood urea nitrogen to creatinine ratio (0.40(0.20-0.78)), and urine dipstick specific gravity (0.95(0.91-0.99)) and protein (0.39(0.23-0.68)). This model showed an AUC of 0.73(0.64-0.81) in the test set, which was similar to the AUC in the external validation cohort [0.74(0.69-0.79)]. The AUC improved to 0.84(0.76-0.91) upon addition of urine interleukin-9 and TNF-α.

CONCLUSIONS: We developed and validated a statistical model that showed a modest AUC for AIN diagnosis, which improved upon addition of urine biomarkers. Future studies could evaluate this model and biomarkers to identify unrecognized cases of AIN.

PMID:34865148 | DOI:10.1093/ndt/gfab346

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Nevin Manimala Statistics

Using Catchment Population to Estimate Sporadic Creutzfeldt-Jakob Disease Incidence

Mil Med. 2021 Dec 4:usab510. doi: 10.1093/milmed/usab510. Online ahead of print.

ABSTRACT

INTRODUCTION: Catchment populations have several uses. A method using catchment population to estimate the incidence of sporadic Creutzfeldt-Jakob disease (sCJD) is described.

MATERIALS AND METHODS: A cohort of nine consecutive patients diagnosed with sCJD, symptom onset spanning 26 months, were observed at a rural tertiary university medical center that has approximately 40,000 hospital discharges annually. An effective catchment population was determined using surrounding county utilization frequency that captured all nine sCJD patients and accounted for over 87% of discharges.

RESULTS: The effective sCJD hospital catchment population was 1.266 million, implying an annual sCJD incidence rate of 3.39 per million (95% CIs, 1.55-6.43), assuming a Poisson distribution for sCJD occurrence.

CONCLUSIONS: This annual incidence rate suggests that many sCJD patients are unrecognized and unreported. An advantage of this catchment population method is independence from death certificate accuracy, important in rare diseases that are both rapidly and invariably fatal. The relative absence of significant healthcare systems competition in this rural population enhances the reliability of this finding. The most likely explanation for the high sCJD incidence rate suggested by this study is enhanced clinical suspicion and improved diagnostic accuracy.

PMID:34865142 | DOI:10.1093/milmed/usab510

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Nevin Manimala Statistics

The ASCEND-ND trial: Study design and participant characteristics

Nephrol Dial Transplant. 2021 Dec 2:gfab318. doi: 10.1093/ndt/gfab318. Online ahead of print.

ABSTRACT

BACKGROUND: Anaemia is common in chronic kidney disease (CKD), and assessment of the risks and benefits of new therapies is important.

METHODS: The Anaemia Study in CKD: Erythropoiesis via a Novel prolyl hydroxylase inhibitor Daprodustat-Non-Dialysis (ASCEND-ND) trial includes adult patients with CKD Stages 3-5, not using erythropoiesis-stimulating agents (ESAs) with screening haemoglobin (Hb) 8-10 g/dL, or receiving ESAs with screening Hb of 8-12 g/dL. Participants were randomised to daprodustat or darbepoetin alfa (1:1) in an open- label trial (steering committee- and sponsor-blinded), with blinded endpoint assessment. The co-primary endpoints are mean change in Hb between baseline and evaluation period (average over Weeks 28 to 52) and time to first adjudicated major adverse cardiovascular (CV) event. Baseline characteristics were compared with those of participants in similar anaemia trials.

RESULTS: Overall, 3872 patients were randomised from 39 countries (median age 67 years, 56% female; 56% White, 27% Asian, and 10% Black). Median baseline Hb was 9.9 g/dL, blood pressure was 135/74 mmHg and eGFR was 18 mL/min/1.73 m2. Among randomised patients, 53% were ESA non-users, 57% had diabetes and 37% had a history of CV disease. At baseline, 61% of participants were using renin- angiotensin system blockers, 55% were taking statin and 49% oral iron. Baseline demographics were similar to those in other large non-dialysis anaemia trials.

CONCLUSION: ASCEND-ND will define the efficacy and safety of daprodustat compared with darbepoetin alfa in the treatment of patients with anaemia associated with CKD not on dialysis.

PMID:34865143 | DOI:10.1093/ndt/gfab318

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Nevin Manimala Statistics

Blood Nicotine Predicts the Behavioral Economic Abuse Liability of Reduced-Nicotine Cigarettes

Nicotine Tob Res. 2021 Dec 3:ntab227. doi: 10.1093/ntr/ntab227. Online ahead of print.

ABSTRACT

BACKGROUND: Cigarette smoking continues to be a major health concern and remains the leading preventable cause of death in the U.S. Recent efforts have been made to determine the potential health and policy benefits of reducing nicotine in combustible cigarettes. The degree to which changes in blood nicotine relate to measures of the abuse liability of reduced-nicotine cigarettes is unknown. The current study examined the relation between blood nicotine and behavioral economic demand measures of cigarettes differing in nicotine content.

METHODS: Using a within-subject design, participants smoked a single cigarette during each experimental session. Cigarettes included the participant’s usual-brand cigarette and SPECTRUM investigational cigarette differing in nicotine level (mg of nicotine to g of tobacco; 15.8mg/g, 5.2mg/g, 2.4mg/g, 1.3mg/g, and 0.4mg/g). During each session, blood was collected at multiple timepoints and behavioral economic demand was assessed. Nonlinear mixed-effects models were used to estimate differences derived intensity (Q0) and change in elasticity (α).

RESULTS: Measures related to blood nicotine decreased in an orderly fashion related to nicotine level and significantly predicted change in elasticity (α), but not derived intensity. No differences in demand parameters between the usual brand and 15.8mg/g cigarettes were observed. However, αwas significantly higher (lower valuation) for 0.4mg/g than 15.8mg/g cigarettes.

CONCLUSIONS: The lowest nicotine level (0.4mg/g) corresponded with the lowest abuse liability (α) compared to the full-strength control (15.8mg/g), with the 1.3mg/g level also resulting in low abuse liability.

IMPLICATIONS: This is the first study examining the relative contributions of nicotine content in cigarettes and blood nicotine levels on the behavioral economic demand abuse liability of cigarettes ranging in nicotine content. Our results suggest blood nicotine and nicotine content both predict behavioral economic demand abuse liability. In addition, our results suggest a nicotine content of 1.3mg/g or lower may be effective at reducing cigarette uptake among first-time (naïve) smokers. Our results largely conform to previous findings suggesting a very low nicotine content cigarette maintains lower abuse liability than full-strength cigarettes.

PMID:34865118 | DOI:10.1093/ntr/ntab227