Bias and variance reduction procedures in non-parametric regression

The purpose of this study is to determine the effect of three improvement methods on nonparametric kernel regression estimators. The improvement methods are applied to the Nadaraya-Watson estimator with cross-validation bandwidth selection, the Nadaraya-Watson estimator with plug-in bandwidth selection, the local linear estimator with plug-in bandwidth selection and a bias corrected nonparametric estimator proposed by Yao (2012), based on cross-validation bandwith selection. The performance of the different resulting estimators are evaluated by empirically calculating their mean integrated squared error (MISE), a global discrepancy measure. The first two improvement methods proposed in this study are based on bootstrap bagging and bootstrap bragging procedures, which were originally introduced and studied by Swanepoel (1988, 1990), and hereafter applied, e.g., by Breiman (1996) in machine learning. Bagging and bragging are primarily variance reduction tools. The third improvement method, referred to as boosting, aims to reduce the bias of an estimator and is based on a procedure originally proposed by Tukey (1977). The behaviour of the classical Nadaraya-Watson estimator with plug-in estimator turns out to be a new recommendable nonparametric regression estimator, since it is not only as precise and accurate as any of the other estimators, but it is also computationally much faster than any other nonparametric regression estimator considered in this study

Hypertriglyceridaemia and the risk of pancreatitis six months post lopinavir/ritonavir initiation

Background: Hypertriglyceridaemia (HTG) is an important risk factor for pancreatitis and cardiovascular disease (CVD), depending on severity. Hypertriglyceridaemia is common in human immunodeficiency virus (HIV) infection and is also a common complication of lopinavir/ritonavir (LPV/r).Objectives: To evaluate the risk of pancreatitis associated with HTG in patients six months post initiation of LPV/r-based therapy in a regional public hospital.Methods: Triglyceride (TG), serum amylase (s-amylase) and CD4+ count values were retrospectively investigated six months post LPV/r-based initiation. Age, gender, previous antiretroviral regimen and period since HIV diagnosis were also recorded.Results: The final sample consisted of 194 patients, 50 males and 144 females; mean (± standard deviation [s.d.]) age was 39.52 (± 9.98) years, and the mean (± s.d.) period since HIV diagnosis was 91.32 (± 25.18) months. Normal TG levels (< 1.70 mmol/L) were detected in only 55% of patients and the rest presented with some degree of HTG. The mean (± s.d.) TG for the entire sample was elevated at 1.94 (± 1.30) mmol/L with the mean (± s.d.) of the males at 2.36 (± 1.74) – statistically higher compared to the females at 1.79 (± 1.08) mmol/L (p = 0.034). No cases of pancreatitis were recorded and the time since HIV diagnosis did not indicate any statistically significant differences in the means of the TG, serum amylase or CD4 count values.Conclusion: Triglyceride levels were not substantially elevated to induce pancreatitis at six months post initiation of LPV/r, but were elevated above the accepted upper normal limit of 1.70 mmol/L which may have implications for cardiovascular risk

Acute changes in haematocrit leading to polycythaemia in late-onset hypogonadism patients that receive testosterone replacement therapy: a South African study

Background: According to the literature, parenteral testosterone replacement therapy (TRT)-induced polycythaemia is associated with cardiovascular events. No or minimal data exist for the prevalence of TRT-induced polycythaemia in lateonset hypogonadism (LOH) patients from South Africa. Polycythaemia is the side effect most frequently associated with parental TRT formulations.Design: This was a quantitative, observational, descriptive, retrospective study.Setting: The study setting was a private practice male clinic in Emalahleni.Subject: An all-inclusive sampling method was used.Outcome measures: The main outcome measure for polycythaemia was haematocrit (Hct). An Hct percentage of > 50% at month 3 (post-treatment initiation) constituted a positive diagnosis for polycythaemia. For the rise in total testosterone (TT) and Hct, the variance was used as documented between pre- and post-treatment initiation.Results: The prevalence of polycythaemia was 34%. A statistically significant increase in both TT and Hct was observed. The Cohen’s d effect size was 0.68 and 0.73, respectively, for TT and Hct.Conclusion: Depot-testosterone undecanoate parenteral formulation induces polycythaemia in LOH patients, where the rise in TT demonstrates the effectiveness of therapy

The Potential Effect of Using the Cockcroft-Gault Method on Tenofovir-Associated Renal Impairment Reports and on Clinical Decisions Regarding Tenofovir Use in Individual Patients: Implications for the Future

Introduction: In Namibia, the Cockcroft-Gault (C-G) method is recommended for monitoring renal function in HIV patients receiving tenofovir disoproxil fumarate (TDF)-containing combination antiretroviral therapy (cART). However, there are concerns with the potential over-reporting of TDF-associated renal impairment. Methods: Retrospective study comparing the renal function of patients receiving 2nd line cART with either C-G or Chronic Kidney Disease-Epidemiology (CKD-EPI) methods. Results: 71 patients were included. The majority (62%) received TDF-containing 1st line ART. All received 2nd-line cART containing TDF/ lamivudine (3TC)/ zidovudine (AZT) and LPV/r. Before switching to 2nd-line cART, 40.8% and 8.5% had abnormal eGFR according to C-G and CKD-EPI methods respectively. During 2nd-line cART, 47.9% and 7% of patients had abnormal eGFR by C-G and CKD-EPI methods, respectively, and 4.1% and 2.8% respectively experienced a decline in eGFR. There was a significant lack of agreement between the two methods. Conclusion: The C-G method has the potential to report more cases of TDF-associated renal impairment. Consequently, national guidelines in Namibia and other pertinent countries should be reviewed if this is the recommended method for monitoring renal function

The association between anthropometric measures and physical performance in black adults of the North West Province, South Africa

OBJECTIVE : This study investigated associations between anthropometric measures and physical performance in black South African adults. It was hypothesized that noninvasive, simple anthropometric measurements, such as calf circumference (CC) and body mass index (BMI), may be useful predictors of physical performance and strength. METHODS : Black human immunodeficiency virus (HIV) negative men and women (aged 32‐93 years) participating in the Prospective Urban and Rural Epidemiology (PURE) study were enrolled at baseline in 2005 = 1428). Men and women's anthropometry, socio‐demographics and physical activity (PA) were assessed at baseline, 5‐ and 10‐year follow‐up. Physical performance (walk speed, chair stand and handgrip strength [HGS]) were assessed at 10‐year follow‐up. Linear regression models adjusted for potential confounders were used to evaluate the association between anthropometric measures and physical performance. RESULTS : The combined overweight and obesity prevalence among both men (P = .02) and women (P < .001) increased significantly over 10 years, with significant increases over time in BMI and CC in the women, whereas PA decreased significantly over time in both men and women (P < .0001). BMI and CC were positively associated with HGS in the men (P = .02, P < .0001) and women (P < .0001), while CC was positively associated with walk speed in men only (P = .006) in the cross‐sectional analysis of 2015 measurements. CONCLUSION : BMI and CC in both men and women were positively associated with HGS, but CC was associated with walk speed in the men only. Our study suggests that CC may be a useful predictor of physical performance in black men and to a limited extent in black women.South African Agency for Science and Technology Advancement, Grant/Award Numbers: 101869, 2069139, FA2006040700010; South‐Africa‐Netherlands Research Programme on Alternatives in Development, Grant/Award Number: 08/15; North‐West University; Health Researchhttp://wileyonlinelibrary.com/journal/ajhb2020-09-10hj2019Human Nutritio

The association between seven-day objectively measured habitual physical activity and 24 hr ambulatory blood pressure: the SABPA study

Few studies have examined objective physical activity in relation to 24 hour ambulatory blood pressure (BP). We aimed to assess the association of seven-day objectively measured habitual physical activity with ambulatory BP in a sample of African and Caucasian school teachers (n=216, age 49.7 yrs) from the Sympathetic Activity and Blood Pressure in Africans prospective cohort study. Hypertension (ambulatory systolic BP≥130 and / or Diastolic BP≥80 mmHg) was prevalent in 53.2% of the sample, particularly in black Africans. The hypertensive group spent significantly more awake time in sedentary activity (51.5 vs. 40.8 % of waking hours, p=0.001), as well as doing less light (34.1 vs. 38.9%, p=0.043) and moderate- (14.0 vs. 19.7%, p=0.032) intensity activities compared with normotensives, respectively. In covariate adjusted models, light intensity activity time was associated with lower 24-hr and day-time ambulatory systolic BP (β=-0.15 ,95% CI: -0.26, -0.05, p=0.004; β=-0.14, -0.24, -0.03, p=0.011) and diastolic BP (β=-0.14, -0.25, -0.03, p=0.015; β=-0.13 ,-0.24, -0.01, p=0.030), as well as resting Systolic BP (β=-0.13 ,-0.24, -0.01, p=0.028). Sedentary time was associated only with 24 hr Systolic BP (β=0.12; 0.01, 0.22), which was largely driven by night time recordings. Participants in the upper sedentary tertile were more likely to be “non-dippers” (odds ratio=2.11, 95% CI, 0.99, 4.46, p=0.052) compared with the lowest sedentary tertile. There were no associations between moderate to vigorous activity and BP. In conclusion, objectively assessed daily light physical activity was associated with ambulatory BP in a mixed ethnic sample

Bias and variance reduction procedures in non-parametric regression

The purpose of this study is to determine the effect of three improvement methods on nonparametric kernel regression estimators. The improvement methods are applied to the Nadaraya-Watson estimator with cross-validation bandwidth selection, the Nadaraya-Watson estimator with plug-in bandwidth selection, the local linear estimator with plug-in bandwidth selection and a bias corrected nonparametric estimator proposed by Yao (2012), based on cross-validation bandwith selection. The performance of the different resulting estimators are evaluated by empirically calculating their mean integrated squared error (MISE), a global discrepancy measure. The first two improvement methods proposed in this study are based on bootstrap bagging and bootstrap bragging procedures, which were originally introduced and studied by Swanepoel (1988, 1990), and hereafter applied, e.g., by Breiman (1996) in machine learning. Bagging and bragging are primarily variance reduction tools. The third improvement method, referred to as boosting, aims to reduce the bias of an estimator and is based on a procedure originally proposed by Tukey (1977). The behaviour of the classical Nadaraya-Watson estimator with plug-in estimator turns out to be a new recommendable nonparametric regression estimator, since it is not only as precise and accurate as any of the other estimators, but it is also computationally much faster than any other nonparametric regression estimator considered in this stud

Goodness-of-fit tests in the Cox proportional hazards model

We consider a variety of tests for testing goodness-of-fit in a parametric Cox proportional hazards (PH) model and compare their performance. Aspects of the model under test include the baseline distribution and time-invariance of covariates. We also test for the PH model itself against a certain generalization. This is done through an extensive Monte Carlo study where we simulate the performance of the tests for these three paired hypotheses. The results show that the tests based on the empirical characteristic function and those based on the empirical Laplace transform have the best overall power performance. It is also found that the distributions of the considered test statistics do not depend on the specific functional form of the covariate functio