An Analytics Approach to Guide Randomized Controlled Trials in Hypertension Management

Blood pressure (BP) is a significant controllable risk factor for cardiovascular disease (CVD), the leading cause of death worldwide. BP comprises two interrelated measurements: systolic and diastolic. CVD risk is minimized at intermediate BP values, a notion known as the J-curve effect. The J-curve effect imposes fundamental trade-offs in simultaneous management of systolic and diastolic BP; however, assessing a comprehensive set of joint systolic/diastolic BP treatment thresholds while explicitly considering the J-curve effect via randomized controlled trials (RCTs) is not feasible because of the time and cost-prohibitive nature of RCTs. In this study, we propose an analytics approach to identify promising joint systolic/diastolic BP threshold levels for antihypertensive treatment. More specifically, using one of the largest longitudinal BP progression data sets, we first build and fit Brownian motion processes to capture simultaneous progression of systolic/diastolic BP at the population level and externally validate our BP progression model on unseen data. We then analytically characterize the hazard ratio, which enables us to compute the optimal treatment decisions. Finally, building upon the optimal joint BP treatment thresholds, we devise a practical and easily implementable approximate policy. We estimate the potential impact of our findings through a simulation study, which indicates that the impact of explicitly considering the J-curve effect and joint systolic/diastolic BP in treatment decisions could be substantial. Specifically, we estimate that between approximately 3,000 and 9,000 premature deaths from cardiovascular disease in the United States could be prevented annually, a finding that could be tested empirically in randomized trials. This paper was accepted by Stefan Scholtes, healthcare management.

Transcutaneous versus Total Serum Bilirubin Measurements in Preterm Infants

<b><i>Introduction:</i></b> Transcutaneous bilirubin (TcB) measurement offers a noninvasive approach for bilirubin screening; however, its accuracy in preterm infants is unclear. This study determined the agreement between TcB and total serum bilirubin (TSB) among preterm infants. <b><i>Methods:</i></b> A multisite prospective cohort study was conducted at 3 NICUs in Ontario, Canada, September 2016 to June 2018. Among 296 preterm infants born at 24^0/7 to 35^6/7 weeks, 856 TcB levels were taken at the forehead, sternum, and before and after the initiation of phototherapy with TSB measurements. Bland-Altman plots and 95% limits of agreement (LOA) expressed agreement between TcB and TSB. <b><i>Results:</i></b> The overall mean TcB-TSB difference was −24.5 μmol/L (95% LOA −103.3 to 54.3), 1.6 μmol/L (95% LOA −73.4 to 76.5) before phototherapy, and −31.1 μmol/L (95% LOA −105.5 to 43.4) after the initiation of phototherapy. The overall mean TcB-TSB difference was −15.2 μmol/L (95% LOA −86.8 to 56.3) at the forehead and −24.4 μmol/L (95% LOA −112.9 to 64.0) at the sternum. The mean TcB-TSB difference was −31.4 μmol/L (95% LOA −95.3 to 32.4) among infants born 24–28 weeks, −25.5 μmol/L (95% LOA −102.7 to 51.8) at 29–32 weeks, and −15.9 μmol/L (95% LOA −107.4 to 75.6) at 33–35 weeks. Measures did not differ by maternal ethnicity. <b><i>Conclusion:</i></b> Among preterm infants, TcB may offer a noninvasive, immediate approach to screening for hyperbilirubinemia with more careful use in preterm infants born at &#x3c;33 weeks’ gestation, as TcB approaches treatment thresholds. Its underestimation of TSB after the initiation of phototherapy warrants the use of TSB for clinical decision-making after the initiation of phototherapy.

Jaundice

The jaundice chapter illustrates how to stabilize newborns with hyperbilirubinemia—a common condition—and avoid their developing severe hyperbilirubinemia. Prevention is accomplished by transcutaneous bilirubin testing, total serum bilirubintests, and the use of nomograms to evaluate risk for hyperbilirubinemia and direct appropriate care. Specific risk factors for jaundice and hyperbilirubinemia, treatment thresholds for phototherapy treatment or exchange transfusion, and a bilirubin-induced neurological dysfunction scoring tool for assessing severity in acute bilirubin encephalopathy cases are included. Related procedures, such as the direct antiglobulin test, volume expansion, and intravenous immunoglobulin administration are described. Focal skills, such as plotting and interpreting the nomograms, are applied in the case scenario.

Diagnostic Properties of a Portable Point-of-Care Method to Measure Bilirubin and a Transcutaneous Bilirubinometer

<b><i>Background:</i></b> Recently, the Bilistick®, a point-of-care instrument to measure bilirubin levels, has been developed. It is fast and cheaper than transcutaneous bilirubin (TCB)-measuring devices, but data on diagnostic properties are scarce. <b><i>Objective:</i></b> This study aimed to compare the performance of the Bilistick® (BM-BS 1.0 – FW version 2.0.1) and the JM-105 bilirubinometer for measuring bilirubin. <b><i>Method:</i></b> This is a prospective study in infants born after ≥32 weeks’ gestation, and/or a birth weight of ≥1,500 g, and a postnatal age ≤14 days in Surabaya, Indonesia. Bilirubin was measured with the Bilistick® System (BM-BS 1.0 – FW version 2.0.1), transcutaneously (TCB) with the JM-105 bilirubinometer, and in serum (TSB) with a routine laboratory technique. Mean differences and 95% limits of agreement (LOA) and correlations were calculated. <b><i>Result:</i></b> We enrolled 149 neonates and 126 had paired measurements of Bilistick® bilirubin, TCB, and TSB. Bilistick® failed in 16 (10.7%) infants. Mean Bilistick® bilirubin-TSB difference was −11 µmol/L (95% LOA: −101 to 79 µmol/L) and <i>r</i> = 0.738 (<i>p</i> &#x3c; 0.001). Mean TCB-TSB difference was 26 μmol/L (95% LOA: −33 to 88) and <i>r</i> = 0.785 (<i>p</i> &#x3c; 0.001). The sensitivity, specificity, PPV, and NPV for Bilistick® bilirubin for a TSB above treatment thresholds were 0.74, 0.84, 0.67, and 0.88, respectively, and for TCB 0.92, 0.64, 0.54, and 0.95, respectively. <b><i>Conclusion:</i></b> The Bilistick® System (BM-BS 1.0 – FW version 2.0.1) underestimates TSB, whereas TCB overestimates TSB in jaundiced Indonesian infants. Further improvement of Bilistick®’s diagnostic accuracy with less false-negative readings is essential to increase its use.