Christopher M. Florkowski

2-Hour accelerated diagnostic protocol to assess patients with chest pain symptoms using contemporary troponins as the only biomarker: the ADAPT trial.

OBJECTIVES The purpose of this study was to determine whether a new accelerated diagnostic protocol (ADP) for possible cardiac chest pain could identify low-risk patients suitable for early discharge (with follow-up shortly after discharge). BACKGROUND Patients presenting with possible acute coronary syndrome (ACS), who have a low short-term risk of adverse cardiac events may be suitable for early discharge and shorter hospital stays. METHODS This prospective observational study tested an ADP that included pre-test probability scoring by the Thrombolysis In Myocardial Infarction (TIMI) score, electrocardiography, and 0 + 2 h values of laboratory troponin I as the sole biomarker. Patients presenting with chest pain due to suspected ACS were included. The primary endpoint was major adverse cardiac event (MACE) within 30 days. RESULTS Of 1,975 patients, 302 (15.3%) had a MACE. The ADP classified 392 patients (20%) as low risk. One (0.25%) of these patients had a MACE, giving the ADP a sensitivity of 99.7% (95% confidence interval [CI]: 98.1% to 99.9%), negative predictive value of 99.7% (95% CI: 98.6% to 100.0%), specificity of 23.4% (95% CI: 21.4% to 25.4%), and positive predictive value of 19.0% (95% CI: 17.2% to 21.0%). Many ADP negative patients had further investigations (74.1%), and therapeutic (18.3%) or procedural (2.0%) interventions during the initial hospital attendance and/or 30-day follow-up. CONCLUSIONS Using the ADP, a large group of patients was successfully identified as at low short-term risk of a MACE and therefore suitable for rapid discharge from the emergency department with early follow-up. This approach could decrease the observation period required for some patients with chest pain. (An observational study of the diagnostic utility of an accelerated diagnostic protocol using contemporary central laboratory cardiac troponin in the assessment of patients presenting to two Australasian hospitals with chest pain of possible cardiac origin; ACTRN12611001069943).

Effect of Vitamin D3 Supplementation on Upper Respiratory Tract Infections in Healthy Adults: The VIDARIS Randomized Controlled Trial

CONTEXT Observational studies have reported an inverse association between serum 25-hydroxyvitamin D (25-OHD) levels and incidence of upper respiratory tract infections (URTIs). However, results of clinical trials of vitamin D supplementation have been inconclusive. OBJECTIVE To determine the effect of vitamin D supplementation on incidence and severity of URTIs in healthy adults. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-controlled trial conducted among 322 healthy adults between February 2010 and November 2011 in Christchurch, New Zealand. INTERVENTION Participants were randomly assigned to receive an initial dose of 200,000 IU oral vitamin D3, then 200,000 IU 1 month later, then 100,000 IU monthly (n = 161), or placebo administered in an identical dosing regimen (n = 161), for a total of 18 months. MAIN OUTCOME MEASURES The primary end point was number of URTI episodes. Secondary end points were duration of URTI episodes, severity of URTI episodes, and number of days of missed work due to URTI episodes. RESULTS The mean baseline 25-OHD level of participants was 29 (SD, 9) ng/mL. Vitamin D supplementation resulted in an increase in serum 25-OHD levels that was maintained at greater than 48 ng/mL throughout the study. There were 593 URTI episodes in the vitamin D group and 611 in the placebo group, with no statistically significant differences in the number of URTIs per participant (mean, 3.7 per person in the vitamin D group and 3.8 per person in the placebo group; risk ratio, 0.97; 95% CI, 0.85-1.11), number of days of missed work as a result of URTIs (mean, 0.76 days in each group; risk ratio, 1.03; 95% CI, 0.81-1.30), duration of symptoms per episode (mean, 12 days in each group; risk ratio, 0.96; 95% CI, 0.73-1.25), or severity of URTI episodes. These findings remained unchanged when the analysis was repeated by season and by baseline 25-OHD levels. CONCLUSION In this trial, monthly administration of 100,000 IU of vitamin D did not reduce the incidence or severity of URTIs in healthy adults. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12609000486224.

Coenzyme Q10: An Independent Predictor of Mortality in Chronic Heart Failure

OBJECTIVES The aim of this study was to investigate the relationship between plasma coenzyme Q(10) (CoQ(10)) and survival in patients with chronic heart failure (CHF). BACKGROUND Patients with CHF have low plasma concentrations of CoQ(10), an essential cofactor for mitochondrial electron transport and myocardial energy supply. Additionally, low plasma total cholesterol (TC) concentrations have been associated with higher mortality in heart failure. Plasma CoQ(10) is closely associated with low-density lipoprotein cholesterol (LDL-C), which might contribute to this association. Therefore we tested the hypothesis that plasma CoQ(10) is a predictor of total mortality in CHF and could explain this association. METHODS Plasma samples from 236 patients admitted to the hospital with CHF, with a median (range) duration of follow-up of 2.69 (0.12 to 5.75) years, were assayed for LDL-C, TC, and total CoQ(10). RESULTS Median age at admission was 77 years. Median (range) CoQ(10) concentration was 0.68 (0.18 to 1.75) micromol/l. The optimal CoQ(10) concentration for prediction of mortality (established with receiver-operator characteristic [ROC] curves) was 0.73 micromol/l. Multivariable analysis allowing for effects of standard predictors of survival--including age at admission, gender, previous myocardial infarction, N-terminal peptide of B-type natriuretic peptide, and estimated glomerular filtration rate (modification of diet in renal disease)--indicated CoQ(10) was an independent predictor of survival, whether dichotomized at the ROC curve cut-point (hazard ratio [HR]: 2.0; 95% confidence interval [CI]: 1.2 to 3.3) or the median (HR: 1.6; 95% CI: 1.0 to 2.6). CONCLUSIONS Plasma CoQ(10) concentration was an independent predictor of mortality in this cohort. The CoQ(10) deficiency might be detrimental to the long-term prognosis of CHF, and there is a rationale for controlled intervention studies with CoQ(10).

A 2-Hour Diagnostic Protocol for Possible Cardiac Chest Pain in the Emergency Department: A Randomized Clinical Trial

IMPORTANCE Patients with chest pain represent a high health care burden, but it may be possible to identify a patient group with a low short-term risk of adverse cardiac events who are suitable for early discharge. OBJECTIVE To compare the effectiveness of a rapid diagnostic pathway with a standard-care diagnostic pathway for the assessment of patients with possible cardiac chest pain in a usual clinical practice setting. DESIGN, SETTING, AND PARTICIPANTS A single-center, randomized parallel-group trial with blinded outcome assessments was conducted in an academic general and tertiary hospital. Participants included adults with acute chest pain consistent with acute coronary syndrome for whom the attending physician planned further observation and troponin testing. Patient recruitment occurred from October 11, 2010, to July 4, 2012, with a 30-day follow-up. INTERVENTIONS An experimental pathway using an accelerated diagnostic protocol (Thrombolysis in Myocardial Infarction score, 0; electrocardiography; and 0- and 2-hour troponin tests) or a standard-care pathway (troponin test on arrival at hospital, prolonged observation, and a second troponin test 6-12 hours after onset of pain) serving as the control. MAIN OUTCOMES AND MEASURES Discharge from the hospital within 6 hours without a major adverse cardiac event occurring within 30 days. RESULTS Fifty-two of 270 patients in the experimental group were successfully discharged within 6 hours compared with 30 of 272 patients in the control group (19.3% vs 11.0%; odds ratio, 1.92; 95% CI, 1.18-3.13; P = .008). It required 20 hours to discharge the same proportion of patients from the control group as achieved in the experimental group within 6 hours. In the experimental group, 35 additional patients (12.9%) were classified as low risk but admitted to an inpatient ward for cardiac investigation. None of the 35 patients received a diagnosis of acute coronary syndrome after inpatient evaluation. CONCLUSIONS AND RELEVANCE Using the accelerated diagnostic protocol in the experimental pathway almost doubled the proportion of patients with chest pain discharged early. Clinicians could discharge approximately 1 of 5 patients with chest pain to outpatient follow-up monitoring in less than 6 hours. This diagnostic strategy could be easily replicated in other centers because no extra resources are required. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12610000766011.

Thiopurine methyltransferase and 6-thioguanine nucleotide measurement: early experience of use in clinical practice

Abstract

Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement Below the Limit of Detection: A Collaborative Meta-analysis

Background High-sensitivity assays for cardiac troponin T (hs-cTnT) are sometimes used to rapidly rule out acute myocardial infarction (AMI). Purpose To estimate the ability of a single hs-cTnT concentration below the limit of detection (<0.005 µg/L) and a nonischemic electrocardiogram (ECG) to rule out AMI in adults presenting to the emergency department (ED) with chest pain. Data Sources EMBASE and MEDLINE without language restrictions (1 January 2008 to 14 December 2016). Study Selection Cohort studies involving adults presenting to the ED with possible acute coronary syndrome in whom an ECG and hs-cTnT measurements were obtained and AMI outcomes adjudicated during initial hospitalization. Data Extraction Investigators of studies provided data on the number of low-risk patients (no new ischemia on ECG and hs-cTnT measurements <0.005 µg/L) and the number who had AMI during hospitalization (primary outcome) or a major adverse cardiac event (MACE) or death within 30 days (secondary outcomes), by risk classification (low or not low risk). Two independent epidemiologists rated risk of bias of studies. Data Synthesis Of 9241 patients in 11 cohort studies, 2825 (30.6%) were classified as low risk. Fourteen (0.5%) low-risk patients had AMI. Sensitivity of the risk classification for AMI ranged from 87.5% to 100% in individual studies. Pooled estimated sensitivity was 98.7% (95% CI, 96.6% to 99.5%). Sensitivity for 30-day MACEs ranged from 87.9% to 100%; pooled sensitivity was 98.0% (CI, 94.7% to 99.3%). No low-risk patients died. Limitation Few studies, variation in timing and methods of reference standard troponin tests, and heterogeneity of risk and prevalence of AMI across studies. Conclusion A single hs-cTnT concentration below the limit of detection in combination with a nonischemic ECG may successfully rule out AMI in patients presenting to EDs with possible emergency acute coronary syndrome. Primary Funding Source Emergency Care Foundation.

A population-based study of bone mineral density in women with longstanding type 1 (insulin dependent) diabetes

This study aimed to explore multiple determinants of BMD (bone mineral density) in 99 women with long-standing type 1 diabetes, recruited from a population based register of insulin users. BMD was measured using DEXA (dual energy X-ray absorptiometry) at the femoral neck and lumbar spine, age adjusted Z scores were calculated and results compared to those of healthy volunteers. The median age of diabetic subjects was 42 years and the median duration of diabetes was 27 years. BMD was positively associated with body mass index and height at both the lumbar spine and femoral neck. There was a positive association with oral contraceptive pill use and lumbar spine BMD, and peripheral vascular disease was negatively associated with femoral neck BMD. No correlation was seen with either age or duration of diabetes and absolute BMD values. Mean Z score at the femoral neck was -0.12 (95% confidence interval -0.37 to +0.12). At the lumbar spine, the corresponding value was -0.21 (-0.44 to +0.02). Pre- and post-menopausal values for the diabetic subjects and healthy volunteers were found to be similar. In summary, axial BMD values in subjects with long-standing diabetes were similar to those observed in healthy non diabetic populations.

The relative effects of fat versus muscle mass on cystatin C and estimates of renal function in healthy young men

Background It is well known that plasma creatinine concentration is affected by muscle mass, while some studies have suggested cystatin C is affected by body mass index (BMI). Our aim was to assess the effects of lean versus fat mass on cystatin C and creatinine derivative equations in estimating glomerular filtration rate (GFR) in healthy young men. Methods Three groups of participants were studied: those classified as normal (BMI 18-25 kg/m 2 with body fat, 30%); muscular subjects (BMI .30 kg/m 2 and body fat, 20%); and obese subjects (BMI .30 kg/m 2 and body fat .30%). All underwent diethylenetriamine pentaacetic acid GFR, bio-electrical impedance and dual-energy X-ray absorptiometry body composition analysis, measurement of plasma cystatin C, creatinine and high-sensitivity C-reactive protein and completed a diet record. Results Cystatin C was highest in the obese group (0.77 mg/L; 95% confidence intervals [CI] 0.69-0.77) and creatinine was highest in the muscular group (90.1 μmol/L; 95% CI 84.3-96.0). On multivariate analysis, body fat and GFR (P = 0.003) were significant determinants of cystatin C; muscle mass and age affected creatinine significantly (P = 0.02). Using cystatin C equations, Le Bricon and Hoek showed significantly lower estimated GFR in the obese group but performed reasonably well within 50%, 30% and 20% of GFR. Creatinine equations showed significant underestimations of GFR for the muscular group. Conclusions Body fat is a significant determinant of cystatin C while creatinine concentration is highly affected by muscle mass and age. Body composition plays an important role in the interpretation of renal function. Cystatin C equations are still accurate in predicting GFR in our healthy male group without chronic kidney disease.

Long-Term High-Dose Vitamin D3 Supplementation and Blood Pressure in Healthy Adults A Randomized Controlled Trial

Previous randomized controlled trials of vitamin D supplementation and blood pressure (BP) mainly have given vitamin D for short periods (<6 months) or at low doses (400 IU per day). This study aims to determine whether long-term high-dose vitamin D taken for 18 months lowers BP. Adults were recruited from a healthcare organization or university into a double-blind controlled trial and randomized to receive either vitamin D3 200 000 IU for 2 months followed by 100 000 IU monthly up to 18 months (n=161) or placebo (n=161). BP was measured at baseline, 5, and 18 months. Subjects had a mean (SD) age of 47.6 (9.7) years, 75% were women, and 94% were of European ancestry (white). Mean (SD) 25-hydroxyvitamin D3 changed from 73 (22) nmol/L at baseline to 124 (28) nmol/L at 18 months in the vitamin D group, and from 71 (22) nmol/L to 56 (22) nmol/L in the placebo group. Mean BP was similar for the vitamin D and placebo groups at baseline (123.4/76.3 versus 122.6/75.6 mm Hg; respectively). The mean change (95% confidence interval) in BP at 18 months minus baseline in the vitamin D group compared with placebo group was −0.6 (−2.8 to 1.6) mm Hg for systolic (P=0.61) and 0.5 (−1.1, 2.2) mm Hg for diastolic (P=0.53). Long-term vitamin D supplementation, which increased mean 25-hydroxyvitamin D3 concentration >100 nmol/L for 18 months, had no effect on systolic or diastolic BP in predominantly white, healthy adults without severe vitamin D deficiency. Beneficial effects on BP cannot be ruled out for other populations.

Cause-specific mortality in insulin-treated diabetic patients: A 20-year follow-up

BACKGROUND Diabetes is one of the most common chronic diseases in Western populations. There have been few large published cohort studies of diabetes with 20 years of follow-up worldwide, and none other than the present one in NZ. AIMS To establish cause-specific death rates, by age and sex in insulin-treated diabetic individuals living in Canterbury, NZ. METHODS Insulin-treated diabetic subjects on the Canterbury Diabetes Registry were followed over 20 years and vital status determined. Following notification of deaths, age- and sex-specific mortality rates, and sex-specific mortality ratios (SMRs) were calculated. RESULTS During follow-up 966 diabetic subjects contributed 13,495 person-years and 525 deaths occurred (261 females and 264 males). At all ages mortality rates were considerably higher than expected mortality. Relative mortalities were increased for cardiovascular (SMR women 3.73, 95% CI: 3.16-4.30; men 3.27, 95% CI: 2.76-3.78), renal (SMR women 5.55, 95% CI: 2.53-8.57; men 7.15, 95% CI: 3.40-10.90), respiratory disease (SMR women 3.31, 95% CI: 1.98-4.63; men 2.32, 95% CI: 1.41-3.23) and malignancy (SMR women 4.99, 95% CI: 2.99-6.99; men 2.19, 95% CI: 1.42-2.96) with cardiovascular disease accounting for the single greatest cause of excess death at all ages. CONCLUSIONS Mortality rates for diabetic individuals remain high, resulting in shortened life spans relative to the general population. To reduce these death rates attention must be paid to the early detection and treatment of CVD and associated risk factors.