A randomized comparison of three prandial insulin dosing algorithms for children and adolescents with Type 1 diabetes.

AIM: To compare systematically the impact of two novel insulin-dosing algorithms (the Pankowska Equation and the Food Insulin Index) with carbohydrate counting on postprandial glucose excursions following a high fat and a high protein meal. METHODS: A randomized, crossover trial at two Paediatric Diabetes centres was conducted. On each day, participants consumed a high protein or high fat meal with similar carbohydrate amounts. Insulin was delivered according to carbohydrate counting, the Pankowska Equation or the Food Insulin Index. Subjects fasted for 5 h following the test meal and physical activity was standardized. Postprandial glycaemia was measured for 300 min using continuous glucose monitoring. RESULTS: 33 children participated in the study. When compared to carbohydrate counting, the Pankowska Equation resulted in lower glycaemic excursion for 90-240 min after the high protein meal (p < 0.05) and lower peak glycaemic excursion (p < 0.05). The risk of hypoglycaemia was significantly lower for carbohydrate counting and the Food Insulin Index compared to the Pankowska Equation (OR 0.76 carbohydrate counting vs. the Pankowska Equation and 0.81 the Food Insulin Index vs. the Pankowska Equation). There was no significant difference in glycaemic excursions when carbohydrate counting was compared to the Food Insulin Index. CONCLUSION: The Pankowska Equation resulted in reduced postprandial hyperglycaemia at the expense of an increase in hypoglycaemia. There were no significant differences when carbohydrate counting was compared to the Food Insulin Index. Further research is required to optimize prandial insulin dosing.

Reproducibility of diagnostic criteria associated with atypical breast cytology.

OBJECTIVE: The aim of this project was to assess the interobserver and intraobserver variability when identifying cytological criteria, which were found to have a statistically significant association with C3 within a workplace environment. METHODS: Sixty C3 cases with known endpoints of malignant, benign proliferative or benign non-proliferative diagnoses were blindly and independently screened by seven experienced cytologists to identify previously reported statistically significant criteria associated with the C3 category. The criteria included the presence of myoepithelial cells or bare bipolar nuclei, cohesiveness, cystic background, papillary fragments with fibrovascular cores and tubular structures. Kappa statistics were used to measure interobserver variability. Two cytologists repeated the process 6 months later to obtain intraobserver data. RESULTS: The interobserver agreement was poor for all criteria except tubules which performed badly. The intraobserver variability for the two cytologists showed that one cytologist achieved moderate intraobserver agreement for all the criteria except cohesion which was poor, whilst the second cytologist showed poor agreement for all criteria. The reasons for the variability are multifactorial and include threshold effects where criteria lack good definition or error in identifying the criteria. CONCLUSION: Interobserver and intraobserver variability remains a significant challenge for cytologists. Despite attempts to define significant criteria associated with C3, good reproducibility could not be achieved. The C3 category is imprecise and highlights the inadequacy of the current classification reporting categories for breast FNA. The impending review of reporting breast cytology by the International Academy of Cytology is timely and appropriate.

Optimizing the combination insulin bolus split for a high-fat, high-protein meal in children and adolescents using insulin pump therapy.

AIMS: To determine the optimum combination bolus split to maintain postprandial glycaemia with a high-fat and high-protein meal in young people with Type 1 diabetes. METHODS: A total of 19 young people (mean age 12.9 ± 6.7 years) participated in a randomized, repeated-measures trial comparing postprandial glycaemic control across six study conditions after a high-fat and high-protein meal. A standard bolus and five different combination boluses were delivered over 2 h in the following splits: 70/30 = 70% standard /30% extended bolus; 60/40=60% standard/40% extended bolus; 50/50=50% standard/50% extended bolus; 40/60=40% standard/60% extended bolus; and 30/70=30% standard/70% extended bolus. Insulin dose was determined using the participant's optimized insulin:carbohydrate ratio. Continuous glucose monitoring was used to assess glucose excursions for 6 h after the test meal. RESULTS: Standard bolus and combination boluses 70/30 and 60/40 controlled the glucose excursion up to 120 min. From 240 to 300 min after the meal, the glucose area under the curve was significantly lower for combination bolus 30/70 compared with standard bolus (P=0.004). CONCLUSIONS: High-fat and high-protein meals require a ≥60% insulin:carbohydrate ratio as a standard bolus to control the initial postprandial rise. Additional insulin at an insulin:carbohydrate ratio of up to 70% is needed in the extended bolus for a high fat and protein meal to prevent delayed hyperglycaemia.

Increasing the protein quantity in a meal results in dose-dependent effects on postprandial glucose levels in individuals with Type 1 diabetes mellitus.

AIM: To determine the glycaemic impact of increasing protein quantities when consumed with consistent amounts of carbohydrate in individuals with Type 1 diabetes on intensive insulin therapy. METHODS: Participants with Type 1 diabetes [aged 10-40 years, HbA1c ≤ 64 mmol/mol (8%), BMI ≤ 91st percentile] received a 30-g carbohydrate (negligible fat) test drink daily over 5 days in randomized order. Protein (whey isolate 0 g/kg carbohydrate, 0 g/kg lipid) was added in amounts of 0 (control), 12.5, 25, 50 and 75 g. A standardized dose of insulin was given for the carbohydrate. Postprandial glycaemia was assessed by 5 h of continuous glucose monitoring. RESULTS: Data were collected from 27 participants (15 male). A dose-response relationship was found with increasing amount of protein. A significant negative relationship between protein dose and mean excursion was seen at the 30- and 60-min time points (P = 0.007 and P = 0.002, respectively). No significant relationship was seen at the 90- and 120-min time points. Thereafter, the dose-response relationship inverted, such that there was a significant positive relationship for each of the 150-300-min time points (P < 0.004). Mean glycaemic excursions were significantly greater for all protein-added test drinks from 150 to 300 min (P < 0.005) with the 75-g protein load, resulting in a mean excursion that was 5 mmol/l higher when compared with the control test drink (P < 0.001). CONCLUSIONS: Increasing protein quantity in a low-fat meal containing consistent amounts of carbohydrate decreases glucose excursions in the early (0-60-min) postprandial period and then increases in the later postprandial period in a dose-dependent manner.

Heads Up: a pilot trial of a psychological intervention to improve nutrition in head and neck cancer patients undergoing radiotherapy.

Malnutrition in head and neck cancer (HNC) patients is common and associated with poorer radiotherapy outcomes including increased mortality. This pilot trial investigates the feasibility and effectiveness of a psychological intervention to improve nutritional status, depression and mortality in HNC patients undergoing radiotherapy. Fifty-nine intervention patients received motivational interviewing and cognitive behavioural therapy compared to 70 historical controls who received treatment as usual. Participants were assessed for nutrition, depression and mortality. There were no significant differences between groups in nutritional status, depression or mortality. Subgroup analyses among patients at greater nutritional risk (cancers of the oral cavity, pharynx, larynx) revealed a potentially clinically important reduction on the PG-SGA and lower mortality (31% of controls vs. 16% intervention; P = 0.03) in favour of the intervention condition. Potential benefits in nutritional status and in mortality in this pilot trial of a psychological intervention among HNC patients at high nutritional risk suggest that a larger randomised controlled trial is warranted.

Influence of dietary protein on postprandial blood glucose levels in individuals with Type 1 diabetes mellitus using intensive insulin therapy.

AIM: To determine the effects of protein alone (independent of fat and carbohydrate) on postprandial glycaemia in individuals with Type 1 diabetes mellitus using intensive insulin therapy. METHODS: Participants with Type 1 diabetes mellitus aged 7-40 years consumed six 150 ml whey isolate protein drinks [0 g (control), 12.5, 25, 50, 75 and 100] and two 150 ml glucose drinks (10 and 20 g) without insulin, in randomized order over 8 days, 4 h after the evening meal. Continuous glucose monitoring was used to assess postprandial glycaemia. RESULTS: Data were collected from 27 participants. Protein loads of 12.5 and 50 g did not result in significant postprandial glycaemic excursions compared with control (water) throughout the 300 min study period (P > 0.05). Protein loads of 75 and 100 g resulted in lower glycaemic excursions than control in the 60-120 min postprandial interval, but higher excursions in the 180-300 min interval. In comparison with 20 g glucose, the large protein loads resulted in significantly delayed and sustained glucose excursions, commencing at 180 min and continuing to 5 h. CONCLUSIONS: Seventy-five grams or more of protein alone significantly increases postprandial glycaemia from 3 to 5 h in people with Type 1 diabetes mellitus using intensive insulin therapy. The glycaemic profiles resulting from high protein loads differ significantly from the excursion from glucose in terms of time to peak glucose and duration of the glycaemic excursion. This research supports recommendations for insulin dosing for large amounts of protein.

Stepped wedge cluster randomised trials: a review of the statistical methodology used and available.

BACKGROUND: Previous reviews have focussed on the rationale for employing the stepped wedge design (SWD), the areas of research to which the design has been applied and the general characteristics of the design. However these did not focus on the statistical methods nor addressed the appropriateness of sample size methods used.This was a review of the literature of the statistical methodology used in stepped wedge cluster randomised trials. METHODS: Literature Review. The Medline, Embase, PsycINFO, CINAHL and Cochrane databases were searched for methodological guides and RCTs which employed the stepped wedge design. RESULTS: This review identified 102 trials which employed the stepped wedge design compared to 37 from the most recent review by Beard et al. 2015. Forty six trials were cohort designs and 45 % (n = 46) had fewer than 10 clusters. Of the 42 articles discussing the design methodology 10 covered analysis and seven covered sample size. For cohort stepped wedge designs there was only one paper considering analysis and one considering sample size methods. Most trials employed either a GEE or mixed model approach to analysis (n = 77) but only 22 trials (22 %) estimated sample size in a way which accounted for the stepped wedge design that was subsequently used. CONCLUSIONS: Many studies which employ the stepped wedge design have few clusters but use methods of analysis which may require more clusters for unbiased and efficient intervention effect estimates. There is the need for research on the minimum number of clusters required for both types of stepped wedge design. Researchers should distinguish in the sample size calculation between cohort and cross sectional stepped wedge designs. Further research is needed on the effect of adjusting for the potential confounding of time on the study power.

Effects of short-term oral corticosteroid intake on dietary intake, body weight and body composition in adults with asthma - a randomized controlled trial.

BACKGROUND: Oral corticosteroids (OCS) are an efficacious treatment for asthma exacerbations, yet risk of adverse effects may decrease patient adherence to therapy. In particular, changes in appetite and dietary intake, which lead to weight gain and changes in body composition, are considered undesirable. OBJECTIVE: To determine whether 10-day OCS therapy in adults with asthma causes changes in leptin, appetite, dietary intake, body weight and body composition. METHODS: Double-blinded, placebo-controlled randomized cross-over trial of 10 days prednisolone (50 mg) in adults with stable asthma (n = 55) (ACTRN12611000562976). Pre- and post-assessment included spirometry, body weight, body composition measured by dual-energy X-ray absorptiometry and bioelectrical impedance analysis, appetite measured using a validated visual analogue scale (VAS) and dietary intake assessed using 4-day food records. Leptin was measured as a biomarker of appetite and eosinophils as an adherence biomarker. Outcomes were analysed by generalized linear mixed models. RESULTS: Subject adherence was confirmed by a significant decrease in blood eosinophils (× 10(9) /L) following prednisolone compared to placebo [Coef. -0.29, 95% CI: (-0.39, -0.19) P < 0.001]. There was no difference in serum leptin (ng/mL) [Coef. 0.13, 95% CI: (-3.47, 3.72) P = 0.945] or appetite measured by VAS (mm) [Coef. -4.93, 95% CI: (-13.64, 3.79) P = 0.267] following prednisolone vs. placebo. There was no difference in dietary intake (kJ/day) [Coef. 255, 95% CI: (-380, 891) P = 0.431], body weight (kg) [Coef. -0.38, 95% CI: (-0.81, 0.05) P = 0.083] or body fat (%) [Coef. -0.31, 95% CI: (-0.81, 0.20) P = 0.230]. Symptoms including sleep and gastrointestinal disturbance were reported significantly more often during prednisolone vs. placebo. CONCLUSIONS AND CLINICAL RELEVANCE: Short-term OCS in stable asthma did not induce significant changes in appetite, dietary intake, body weight or composition, although other adverse effects may require medical management. This evidence may assist in increasing medication adherence of asthmatics prescribed OCS for exacerbations.

The fraction of exhaled nitric oxide improves prediction of clinical allergic reaction to peanut challenge in children.

BACKGROUND: Retrospective studies of childhood peanut allergy demonstrate serum-specific IgE (IgE) levels against the peanut allergen Ara h2 may help predict a clinical reaction at food challenge. Fraction of exhaled nitric oxide (FeNO) is a non-invasive tool correlating to allergic airways inflammation and has been independently associated with increased food-specific IgE. OBJECTIVE: To assess the validity of serum-specific Ara h2 IgE measured prospectively to diagnose peanut allergy and explore the utility of FeNO as a non-invasive screening tool for childhood food challenge. METHODS: We recruited 53 participants from a cohort of consecutive children scheduled for an open-labelled peanut food challenge (OFC) by their paediatric allergist. Participants underwent skin prick test (SPT) measurement for sensitization to whole peanut extract, and serum was collected for Ara h2-specific IgE. FeNO was also measured in all cooperative children before the challenge. OFC and assessment of reaction were undertaken by clinicians blinded to test results. RESULTS: Ara h2-specific IgE and FeNO each showed improved diagnostic accuracy when compared to SPT. Receiver operator characteristic curve analysis gave an area under the curve (AUC) for Ara h2 sIgE of 0.84 (95% CI, 0.72-0.96). The AUC for FeNO, 0.83 (95% CI, 0.71-0.95), was equivalent to that of Ara h2. Combined AUC for SPT, sIgE to Ara h2 and FeNO was 0.96 (95% CI 0.90-1.00). There was no correlation between FeNO and serum nitrite levels (rs = -0.13, P = 0.6, n = 18). CONCLUSION AND CLINICAL RELEVANCE: Prospectively measured Ara h2-specific IgE improves diagnostic accuracy and reduces unsuccessful challenge to peanut. FeNO levels may provide improved diagnostic accuracy in a paediatric population undergoing OFC. The proposed FeNO-based diagnostic algorithm requires further validation studies.

In children using intensive insulin therapy, a 20-g variation in carbohydrate amount significantly impacts on postprandial glycaemia.

AIM: To determine if an insulin dose calculated for a meal containing 60 g carbohydrate maintains postprandial glycaemic control for meals containing 40, 50, 70 or 80 g carbohydrate. METHODS: Thirty-four young people (age range 8.5-17.7 years) using intensive insulin therapy consumed five test breakfasts with equivalent fat, protein and fibre contents but differing carbohydrate quantities (40, 50, 60, 70 and 80 g of carbohydrate). The preprandial insulin dose was the same for each meal, based on the subject's usual insulin:carbohydrate ratio for 60 g carbohydrate. Continuous glucose monitoring was used to monitor postprandial glucose over 180 min. RESULTS: The 40-g carbohydrate meal resulted in significantly more hypoglycaemia than the other meals (P = 0.003). There was a one in three chance of hypoglycaemia between 120 and 180 min if an insulin dose for 60 g carbohydrate was given for 40 g carbohydrate. The glucose levels of subjects on the 80-g meal were significantly higher than the 60- and 70-g carbohydrate meals at all time points between 150 and 180 min (P < 0.01). Subjects consuming the 80-g meal were more likely to have significant hyperglycaemia (blood glucose levels ≥ 12 mmol/l) compared with the other meals (P < 0.001). CONCLUSIONS: In patients using intensive insulin therapy, an individually calculated insulin dose for 60 g carbohydrate results in postprandial hypoglycaemia or hyperglycaemia for meals containing 40 and 80 g carbohydrate. To calculate mealtime insulin in order to maintain postprandial control, carbohydrate estimations should be within 10 g of the actual meal carbohydrate.

Death, dependency and health status 90 days following hospital admission for acute stroke in NSW.

BACKGROUND: Stroke is an Australian health priority area causing considerable levels of disability. We report 90-day outcomes for a cohort of acute stroke patients in New South Wales (NSW), Australia prior to randomization to a large cluster randomized controlled trial (CRCT), the Quality in Acute Stroke Care (QASC) trial. AIMS: This paper describes prospectively collected, 90-day outcome data for a cohort of NSW stroke patients, providing pre-intervention data for the QASC trial. METHODS: A consecutive sample of patients from acute stroke units in NSW was recruited. We measured patient death, disability (modified Rankin Score (mRS)), dependency (Barthel Index (BI)) and Health Status (Medical Outcomes Short-Form Health Survey (SF-36)) 90 days post-hospital admission. We also collected self-reported healthcare utilization and patient satisfaction with health professionals' advice and management to reduce risk of subsequent stroke. RESULTS: Ninety-day outcome data were obtained for 687 patients, of which, 335 (49%) had an mRS ≥2; 44 patients (6.4%) had died. For the 643 surviving patients, the mean BI was 87.2 (SD 21.9) and the mean scores for SF-36 Physical Component Summary score and Mental Component Summary score were 46.2 (SD 10.1) and 46.3 (SD 12.6) respectively. CONCLUSIONS: In this pre-intervention cohort of selected acute stroke inpatients, stroke severity was mild to moderate and subsequent clinical outcomes were favourable in the majority. The findings from this study provide a comprehensive description of 90-day health outcomes of patients who have experienced a mild-moderate stroke managed in stroke care units across metropolitan NSW and provide valuable data to inform the subsequent cluster trial.

Can children with Type 1 diabetes and their caregivers estimate the carbohydrate content of meals and snacks?

AIMS: Carbohydrate (CHO) counting allows children with Type 1 diabetes to adjust mealtime insulin dose to carbohydrate intake. Little is known about the ability of children to count CHO and whether a particular method for assessing CHO quantity is better than others. We investigated how accurately children and their caregivers estimate carbohydrate, and whether counting in gram increments improves accuracy compared with CHO portions or exchanges. METHODS: One hundred and two children and adolescents (age range 8.3-18.1 years) on intensive insulin therapy and 110 caregivers independently estimated the CHO content of 17 standardized meals (containing 8-90 g CHO), using whichever method of carbohydrate quantification they had been taught (gram increments, 10-g portions or 15-g exchanges). RESULTS: Seventy-three per cent (n = 2530) of all estimates were within 10-15 g of actual CHO content. There was no relationship between the mean percentage error and method of carbohydrate counting or glycated haemoglobin (HbA(1c)) (P > 0.05). Mean gram error and meal size were negatively correlated (r = -0.70, P < 0.0001). The longer children had been CHO counting the greater the mean percentage error (r = 0.173, P = 0.014). Core foods in non-standard quantities were most frequently inaccurately estimated, while individually labelled foods were most often accurately estimated. CONCLUSIONS: Children with Type 1 diabetes and their caregivers can estimate the carbohydrate content of meals with reasonable accuracy. Teaching CHO counting in gram increments did not improve accuracy compared with CHO portions or exchanges. Large meals tended to be underestimated and snacks overestimated. Repeated age-appropriate education appears necessary to maintain accuracy in carbohydrate estimations.

Does an advanced insulin education programme improve outcomes and health service use for people with Type 2 diabetes? A 5-year follow-up of the Newcastle Empowerment course.

OBJECTIVE: To show that an advanced diabetes education programme delivers sustained benefits to people with diabetes prescribed insulin and healthcare providers over and above those provided by basic diabetes education. METHODS: An historical cohort study of 68 people with Type 1 and 51 people with Type 2 diabetes on insulin who attended the 4-day Newcastle Empowerment programme in 2001 and 2002 compared with 71 people with Type 1 and 312 people with Type 2 diabetes who attended only the basic 4-day insulin education programme over the same period, followed until 2007. Primary outcome was all hospital admissions and emergency visits; secondary outcomes were the composite of first cardiac event or death and readmission for diabetes complications. Cox-proportional hazards regression was used to analyse Type 1 and Type 2 diabetes separately. RESULTS: The empowerment programme significantly delayed time to first hospital admission/visit for patients with Type 2 diabetes; the hazard ratio (HR) of 0.41 (P = 0.01) translates into a delay of almost 3 years; this was partly driven by a significant reduction in cardiovascular events and mortality (HR = 0.24, P = 0.01). These effects were not seen for people with Type 1 diabetes. CONCLUSIONS: A one-time, advanced diabetes education programme teaching intensive insulin self-management with an empowerment style can lead to sustained improvement in patient outcomes and reduce use of hospital services for people with Type 2 diabetes on insulin.

Maternal vitamin D deficiency, ethnicity and gestational diabetes.

AIMS: Vitamin D deficiency has been linked to impaired glucose metabolism. We determined whether serum 25-hydroxyvitamin D (25OHD) is associated with glucose metabolism in pregnant women and the effect of ethnicity on this relationship. METHODS: We analysed serum 25OHD concentrations in 307 pregnant women attending a metropolitan obstetric clinic between October 2003 and May 2005. Measurements from 264 of the women were taken at the time of glucose tolerance testing at mid-gestation, a population therefore at increased risk for gestational diabetes. Pearson correlation analysis was used to test for univariate linear relationships between the natural log of serum 25OHD (ln-25OHD) and other variables. Multiple regression analysis was used to adjust for confounding factors. RESULTS: Mean serum 25OHD concentration was 53.8 +/- 23.9 nmol/l (sd). Ln-25OHD was negatively correlated with serum parathyroid hormone as expected (r -0.24, confidence intervals -0.35 to -0.12). Ln-25OHD was also negatively correlated with fasting plasma glucose (r-0.20, -0.31 to -0.08), fasting insulin (r -0.20, -0.31 to -0.08) and insulin resistance as calculated by homeostasis model assessment (r -0.21, -0.32 to -0.09). The association between fasting glucose and log-transformed 25OHD concentration was of borderline significance after accounting for ethnicity, age and body mass index in multivariate analyses (-0.13, -0.26 to 0.01). The odds ratio of gestational diabetes in women with 25OHD < 50 nmol/l did not reach statistical significance (1.92, 95% confidence interval 0.89-4.17). CONCLUSIONS: Maternal 25OHD concentrations are inversely related to fasting glucose, although further studies are required to establish whether this is independent of the effects of ethnic background.

Outcome with calcium channel antagonists after myocardial infarction: a community-based study.

OBJECTIVES: We sought to estimate the risk of death and recurrent myocardial infarction associated with the use of calcium antagonists after myocardial infarction in a population-based cohort study. BACKGROUND: Calcium antagonists are commonly prescribed after myocardial infarction, but their long-term effects are not well established. METHODS: Patients 25 to 69 years old with a suspected myocardial infarction were identified and followed up through a community-based register of myocardial infarction and cardiac death (part of the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease [MONICA] Project in Newcastle, Australia). Data were collected by review of medical records, in-hospital interview and review of death certificates. RESULTS: From 1989 to 1993, 3,982 patients with a nonfatal suspected myocardial infarction were enrolled in the study. At hospital discharge, 1,001 patients were treated with beta-adrenergic blocking agents, 923 with calcium antagonists, 711 with both beta-blockers and calcium antagonists and 1,346 with neither drug. Compared with patients given beta-blockers, patients given calcium antagonists were more likely to suffer myocardial infarction or cardiac death (adjusted relative risk [RR] 1.4, 95% confidence interval [CI] 1.0 to 1.9), cardiac death (RR 1.6, 95% CI 1.0 to 2.7) and death from all causes (RR 1.7, 95% CI 1.1 to 2.6). Compared with patients given neither beta-blockers nor calcium antagonists, patients given calcium antagonists were not at increased risk of myocardial infarction or cardiac death (RR 1.0, 95% CI 0.8 to 1.3), cardiac death (RR 0.9, 95% CI 0.6 to 1.2) or death from all causes (RR 1.0, 95% CI 0.7 to 1.3). No excess in risk of myocardial infarction or cardiac death was observed among patients taking verapamil (RR 0.9, 95% CI 0.6 to 1.6), diltiazem (RR 1.1, 95% CI 0.8 to 1.4) or nifedipine (RR 1.3, 95% CI 0.7 to 2.2) compared with patients taking neither calcium antagonists nor beta-blockers. CONCLUSIONS: These results are consistent with randomized trial data showing benefit from beta-blockers after myocardial infarction and no effect on the risk of recurrent myocardial infarction and death with the use of calcium antagonists. Comparisons between beta-blockers and calcium antagonists favor beta-blockers because of the beneficial effects of beta-blockers and not because of adverse effects of calcium antagonists.

Risk of primary and recurrent acute myocardial infarction from lipoprotein(a) in men and women.

OBJECTIVES: This study sought to examine whether lipoprotein(a) concentrations were risk factors for a first acute and recurrent myocardial infarction. BACKGROUND: There is conflicting evidence concerning the risk of acute myocardial infarction from lipoprotein(a). No studies have examined the risk of recurrent acute myocardial infarction from lipoprotein(a), and few have addressed the risk in women. METHODS: This was a population-based case-control study of 893 men and women 35 to 69 years old participating in the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Project in Newcastle, Australia in 1993 to 1994. Case and control patients were classified into those with and without a previous myocardial infarction, and median lipoprotein(a) concentrations were compared after adjusting for other variables. Quintiles of lipoprotein(a) concentration were also examined. RESULTS: Compared with control subjects without a previous myocardial infarction, median lipoprotein(a) concentrations increased from case patients with a first myocardial infarction (15 mg/liter higher, 95% confidence interval [CI] -36 to 60) to control patients with a previous myocardial infarction (159 mg/ liter higher, 95% CI 40 to 278) and case patients with a previous myocardial infarction (60 mg/liter higher, 95% CI -16 to 136, p < 0.01, test for trend). Women had significantly higher lipoprotein(a) concentrations than men (median 71 mg/liter higher, 95% CI 23 to 118). The highest quintile of lipoprotein(a) (>550 mg/liter) was a significant risk factor for a first acute myocardial infarction (odds ratio [OR] 1.77, 95% CI 1.03 to 3.03); but in those with a previous myocardial infarction, the highest quintile was not associated with recurrent myocardial infarction (OR 0.84, 95% CI 0.30 to 2.37). CONCLUSIONS: High lipoprotein(a) concentrations may be a marker of vascular or tissue injury or may be associated with other genetic or environmental factors that cause acute myocardial infarction. Currently, lipoprotein(a) measurement cannot be recommended for assessment of risk for acute myocardial infarction.

Survival among hospital in-patients with troponin T elevation below levels defining myocardial infarction.

BACKGROUND: Cardiac troponin T (cTnT) has an accepted place in the management of patients presenting with suspected acute coronary syndrome (ACS). Uncertainty remains about the significance and interpretation of elevated cTnT below the cut-off levels defining myocardial infarction (0.1 microg/l). AIM: To compare the mortality risks for elevation of cTnT in the ranges 0.01-0.029 microg/l, 0.03-0.099 microg/l and <0.01 microg/l. DESIGN: Retrospective record study in three hospitals. METHODS: All cTnT measurements with values in the range >0.01-0.099 microg/l analysed during January 2002 were extracted from clinical biochemistry laboratory databases. Following agreed exclusion criteria, 179 patients with cTnT in the range 0.01-0.099 microg/l and 60 patients <0.01 microg/l were selected at random from across the three sites. Six-month follow-up was completed by review of case notes and contact with the patients' GP. RESULTS: There was a graded increase in mortality with increasing cTnT, although only achieving statistical significance for patients in the 0.03-0.099 microg/l range. The graded increase in relative risk with cTnT was weaker after adjustment for potential confounding factors DISCUSSION: We found a trend for worse survival with increasing cTnT within the range 0.01-0.099 microg/l in unselected patient populations presenting with possible acute coronary syndrome. This suggests that the combined effects of assay imprecision and co-morbidity should be taken into account when interpreting borderline elevation of cTnT. The use of a cut-off based on current standards of assay precision should be used to define the sensitivity of cTnT as biochemical evidence of ischaemic cardiac damage and as an indicator of mortality risk. This level is likely to be between 0.03 and 0.1 microg/l.

Population impact of stricter adherence to recommendations for pharmacological and lifestyle interventions over one year in patients with coronary heart disease.

STUDY OBJECTIVE: To assess the potential number of lives saved associated with the full implementation of aspects of the National Service Framework (NSF) for coronary heart disease (CHD) in England using recently developed population impact measures. DESIGN: Modelling study. SETTING: Primary care. DATA SOURCES: Published data on prevalence of acute myocardial infarction and heart failure, baseline risk of mortality, the relative risk reduction associated with different interventions and the proportion treated, eligible for treatment and adhering to each intervention. MAIN RESULTS: Adopting the NSF recommendations for pharmacological interventions would prevent an extra 1027 (95% CI 418 to 1994) deaths in post-acute myocardial infarction (AMI) patients and an extra 37 899 (95% CI 25 690 to 52 503) deaths in heart failure patients in the first year after diagnosis. Lifestyle based interventions would prevent an extra 848 (95% CI 71 to 1 614) deaths in post-AMI patients and an extra 7249 (95% CI 995 to 16 696) deaths in heart failure patients. CONCLUSIONS: Moving from current to "best" practice as recommended in the NSF will have a much greater impact on one year mortality rates among heart failure patients compared with post-AMI patients. Meeting pharmacological based recommendations for heart failure patients will prevent more deaths than meeting lifestyle based recommendations. Population impact numbers can help communicate the impact on a population of the implementation of guidelines and, when created using local data, could help policy makers assess the local impact of implementing a range of health care targets.

Case fatality after an acute cardiac event: the effect of smoking and alcohol consumption.

The objective of this study was to use a population-based register of acute cardiac events to investigate the association between survival after an acute event and history of smoking and alcohol consumption. The population was all residents of the Lower Hunter Region of Australia aged 25 to 69 years who suffered myocardial infarction or sudden cardiac death between 1986 and 1994. Among 10,170 events, 2504 resulted in death within 28 days. After adjusting for sex, age and medical history, current smokers had a similar risk of dying after an acute cardiac event to never-smokers [odds ratio (OR)=1.10, 95% confidence interval (CI) 0.94-1.29]. People who consumed more than 8 alcoholic drinks per day on more than 2 days per week (OR=1.93, 95% CI 1.39-2.69) and former moderate to heavy drinkers (OR=4.59, 95% CI 3.65-5.76) were more likely to die than people who were nondrinkers. The results of this large community study, suggesting no effect of smoking on case fatality and an increased risk of death after an acute cardiac event for heavy drinkers and former moderate to heavy drinkers, highlight the importance of a population view of case fatality. These results can also shed some light on reasons for the paradoxical results from clinical trials.