Impact of female obesity and assisted reproduction on uncomplicated pregnancies and healthy births: a study of 428 336 births in Flanders.

STUDY QUESTION: What is the impact of BMI on uncomplicated pregnancies and healthy births in women who did or did not have medically assisted reproduction (MAR, i.e. ART or hormonal stimulation without manipulation of eggs or embryos) in the Flanders region (Belgium)? SUMMARY ANSWER: Women with a higher BMI who use MAR are at the highest risk of pregnancy and birth complications. WHAT WE KNOW ALREADY: Medically assisted reproduction (MAR) is used increasingly worldwide and is associated with increased risk of adverse perinatal outcomes. Obesity is also increasing globally and obese women are more likely to seek MAR since obesity is associated with infertility. When obese women undergo MAR, the risk of adverse outcomes may be enhanced but it is not clear to what extent. STUDY DESIGN, SIZE, DURATION: We conducted a registry-based study using the data from the Study Centre for Perinatal epidemiology database for years 2009-2015, region of Flanders, Belgium. This included 428 336 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The average age was 30.0 years (SD 4.78), 194 061 (45.31%) were nulliparous, and 6.3% (n = 26 971) conceived with MAR. We examined the association of BMI and MAR with the following composite primary outcomes: 'uncomplicated pregnancy and birth' and 'healthy baby'. We conducted Poisson regression and adjusted for maternal age, parity, gestational weight gain, smoking and previous caesarean section. MAIN RESULTS AND THE ROLE OF CHANCE: In our study, 36.80% (n = 157 623) of women had an uncomplicated pregnancy and birth according to the definition used. The predicted probability of having an uncomplicated pregnancy and birth for women with a BMI of 25 kg/m2 who conceived spontaneously was 0.33 (0.32 to 0.35), while it was 0.28 (0.24 to 0.32) for women who used hormonal stimulation and 0.26 (0.22 to 0.29) for women who used IVF/ICSI. This probability reduced with increasing BMI category for both MAR and non-MAR users. For women with a BMI of 30 kg/m2, the predicted probability of having an uncomplicated pregnancy and birth was 0.28 (0.26 to 0.30) for women who conceived spontaneously, and 0.22 (0.16 to 0.29) and 0.20 (0.14 to 0.26) for women who used hormonal stimulation only or IVF/ICSI, respectively. The predicted probability of having a healthy baby for women with a BMI of 25 kg/m2 who conceived spontaneously was 0.92 (0.91 to 0.93), 0.89 (0.87 to 0.92) for women who used hormonal stimulation only and 0.85 (0.84 to 0.87) for women who used IVF/ICSI. LIMITATIONS, REASONS FOR CAUTION: The database did not include data on socio-economic status, pre-pregnancy morbidities and paternal BMI. Subsequently, we could not adjust for these factors in the analysis. WIDER IMPLICATIONS OF THE FINDINGS: Obese women who use MAR are at the highest risk of pregnancy and birth complications. This increase in interventions also has cost and resource implications which is relevant for funding policies. Weight loss interventions prior to MAR seem plausible but their (cost-) effectiveness needs urgent investigation. STUDY FUNDING/COMPETING INTEREST(S): F.W. received an Erasmus Plus training grant to visit A.B., L.A. and R.D. and conducted this study during this visit. The authors have no competing interest to declare. TRIAL REGISTRATION NUMBER: N/A.

A prospective study of placental growth factor in twin pregnancy and development of a dichorionic twin pregnancy specific reference range.

OBJECTIVE: To develop a dichorionic twin pregnancy specific reference range for placental growth factor (PlGF), and to compare gestation-specific placental growth factor levels in twin pregnancies later complicated by pre-eclampsia, hypertensive disorder of pregnancy or fetal growth restriction with control pregnancies. DESIGN: Prospective observational study. SETTING: Single large tertiary maternity unit in Ireland. POPULATION OR SAMPLE: Women with a twin pregnancy. METHODS: Consenting pregnant women, across a variety of gestations, had a single blood sample taken at one time-point only during their pregnancy. The plasma was initially biobanked and PlGF was measured later in batches using the point of care Triage® PlGF test. MAIN OUTCOME MEASURES: Development of pre-eclampsia, hypertensive disorder of pregnancy or fetal growth restriction. RESULTS: Placental growth factor levels in uncomplicated dichorionic twin pregnancies were significantly lower in the women who later developed pre-eclampsia than in the controls at all gestational intervals. In those that later developed any hypertensive disorder of pregnancy, median PlGF was lower only in those recruited before 24 weeks of gestation, whereas in infants with a customised birthweight below the third centile, PlGF was lower only in those sampled after 24 weeks of gestation. CONCLUSIONS: Placental growth factor levels in twin pregnancy differ significantly between those women with a pregnancy that will later be complicated by pre-eclampsia and those that will not. This difference is present many weeks before clinical signs or symptoms of disease are present. Using cross-sectional values from uncomplicated twin pregnancies, we have developed a dichorionic twin pregnancy specific reference range for PlGF. TWEETABLE ABSTRACT: Placental growth factor levels in twin pregnancy differ significantly between women that will later develop pre-eclampsia and those that will not.

Impact of improved observed hand hygiene on bloodstream infection rates in Ireland. A prospective segmented regression analysis, 2009-2016.

Participation in European surveillance for bloodstream infection (BSI) commenced in Ireland in 1999 with all laboratories (n = 39) participating by 2014. Observational hand hygiene auditing (OHHA) was implemented in 2011. The aim of this study was to evaluate the impact of OHHA on hand hygiene compliance, alcohol hand rub (AHR) procurement and the incidence of sensitive and resistant Staphylococcus aureus and Enterococcus faecium and faecalis BSI. A prospective segmented regression analysis was performed to determine the temporal association between OHHA and outcomes. Observed hand hygiene improved from 74.7% (73.7-75.6) in 2011 to 90.8% (90.1-91.3) in 2016. AHR procurement increased from 20.1 l/1000 bed days used (BDU) in 2009 to 33.2 l/1000 BDU in 2016. A pre-intervention reduction of 2% per quarter in the ratio of methicillin sensitive Staphylococcus aureus BSI/BDU stabilized in the time period after the intervention (P < 0.01). The ratio of Methicillin resistant Staphylococcus aureus (MRSA) BSI/BDU was decreasing by 5% per quarter pre-intervention, this slowed to 2% per quarter post intervention, (P < 0.01). There was no significant change in the ratio of vancomycin sensitive (P = 0.49) or vancomycin resistant (P = 0.90) Enterococcus sp. BSI/BDU post intervention. This study shows national OHHA increased observed hand hygiene compliance and AHR procurement, however there was no associated reduction in BSI.

Health service utilization and related costs attributable to diabetes.

AIMS: To estimate the health service use and direct healthcare costs attributable to diabetes using best available data and methods. METHODS: A nationally representative sample of adults aged ≥50 years was analysed (n=8107). Health service use in the previous 12 months included the number of general practitioner visits, outpatient department visits, hospital admissions, and accident and emergency department attendances. Multivariable negative binomial regression was used to estimate the associations between diabetes and frequency of visits. Average marginal effects were applied to unit costs for each health service and extrapolated to the total population, calculating the incremental costs associated with diabetes. RESULTS: The prevalence of diabetes was 8.0% (95% CI: 7.4, 8.6). In fully adjusted models, diabetes was associated with additional health service use. Compared to those without diabetes, people with diabetes have, on average, 1.49 (95% CI: 1.10, 1.88) additional general practitioner visits annually. Diabetes was associated with an 87% increase in outpatient visits, a 52% increase in hospital admissions and a 33% increase in accident and emergency department attendances (P<0.001). The incremental cost of this additional service use, nationally, is an estimated €88,894,421 annually, with hospital admissions accounting for 67% of these costs. CONCLUSION: Using robust methods, we identified substantially increased service use attributable to diabetes across the health system. Our findings highlight the urgent need to invest in the prevention and management of diabetes.

Morning surge in blood pressure using a random-effects multiple-component cosinor model.

Blood pressure (BP) fluctuates throughout the day. The pattern it follows represents one of the most important circadian rhythms in the human body. For example, morning BP surge has been suggested as a potential risk factor for cardiovascular events occurring in the morning, but the accurate quantification of this phenomenon remains a challenge. Here, we outline a novel method to quantify morning surge. We demonstrate how the most commonly used method to model 24-hour BP, the single cosinor approach, can be extended to a multiple-component cosinor random-effects model. We outline how this model can be used to obtain a measure of morning BP surge by obtaining derivatives of the model fit. The model is compared with a functional principal component analysis that determines the main components of variability in the data. Data from the Mitchelstown Study, a population-based study of Irish adults (n = 2047), were used where a subsample (1207) underwent 24-hour ambulatory blood pressure monitoring. We demonstrate that our 2-component model provided a significant improvement in fit compared with a single model and a similar fit to a more complex model captured by b-splines using functional principal component analysis. The estimate of the average maximum slope was 2.857 mmHg/30 min (bootstrap estimates; 95% CI: 2.855-2.858 mmHg/30 min). Simulation results allowed us to quantify the between-individual SD in maximum slopes, which was 1.02 mmHg/30 min. By obtaining derivatives we have demonstrated a novel approach to quantify morning BP surge and its variation between individuals. This is the first demonstration of cosinor approach to obtain a measure of morning surge.

Trends in blindness due to diabetic retinopathy among adults aged 18-69years over a decade in Ireland.

AIMS: To describe trends in the incidence of visual impairment and blindness due to diabetic retinopathy among adults aged 18-69years in Ireland between 2004 and 2013. METHODS: Data on visual impairment due to diabetic retinopathy in adults aged 18-69years or over who are registered with the National Council for the Blind of Ireland, (2004-2013) were analysed. Annual incidence rates were calculated for the adult population and the population with diagnosed diabetes. Poisson regression was used to test for changes in rates over time. The relative, attributable and population risk of blindness and visual impairment due to diabetic retinopathy were calculated for 2013. RESULTS: Over the decade, the prevalence of diagnosed diabetes increased from 2.1% to 3.6%. Among people with diagnosed diabetes, the incidence of visual impairment due to diabetic retinopathy increased from 6.4 (95% CI 2.4-13.9) per 100,000 in 2004 to 11.7 (95% CI 5.9-21.0) per 100,000 in 2013. The incidence of blindness due to diabetic retinopathy varied from 31.9 per 100,000 (95% CI 21.6-45.7) in 2004 to 14.9 per 100,000 (95% CI 8.2-25.1) in 2013. CONCLUSIONS: Our findings indicate the need for increased attention to preventive measures for microvascular complications among adults with diabetes in Ireland. Retinopathy screening has been standardised in Ireland, these findings provide useful baseline statistics to monitor the impact of this population-based screening programme.

The prevalence of Type 2 diabetes and related complications in a nationally representative sample of adults aged 50 and over in the Republic of Ireland.

AIM: To investigate the prevalence of diagnosed Type 2 diabetes and its related complications in a nationally representative sample of older adults in the Republic of Ireland. METHODS: Cross-sectional analysis of a population-based sample of adults aged ≥ 50 years from the first wave of The Irish Longitudinal Study on Ageing (TILDA), (2009-2011). Diagnosed Type 2 diabetes prevalence was estimated by self-report or the use of oral hypoglycaemic agents. The prevalence of microvascular and macrovascular complications was determined by self-report. RESULTS: Diagnosed Type 2 diabetes prevalence was 8.4% [95% confidence interval (CI): 7.8-9.0%] and was higher among men [10.3% (95% CI: 9.4-11.2%)] than women [6.6% (95% CI: 5.9-7.5%)]; P ≤ 0.001. Among participants with diagnosed Type 2 diabetes, the overall prevalence of microvascular complications was 26.0% (95% CI: 22.4-30.0%) with no evidence of gender-specific differences (P = 0.7). The overall prevalence of macrovascular complications was 15.1% (95% CI: 12.2-18.4%) and was higher among men [17.8% (95% CI: 14.3-23.1%)] than women [11.4% (95% CI: 7.7-16.4%)]; P ≤ 0.001. CONCLUSIONS: In the absence of a national diabetes register, these findings provide a robust estimate of the national prevalence of diagnosed Type 2 diabetes and level of complications among adults aged 50 years and over in Ireland.

Validation of diet and urinary excretion derived estimates of sodium excretion against 24-h urine excretion in a worksite sample.

BACKGROUND AND AIMS: To validate diet and urinary excretion derived estimates of sodium intake against those derived from 24-h urine collections in an Irish manufacturing workplace sample. METHODS AND RESULTS: We have compared daily sodium (Na) excretion from PABA validated 24-h urine collections with estimated daily sodium excretion derived from the following methods: a standard Food Frequency Questionnaire (FFQ), a modified 24-h dietary recall method, arithmetic extrapolations from morning and evening spot urine samples, predicted sodium excretion from morning and evening spot urine samples using Tanaka's, Kawasaki's and the INTERSALT formula. All were assessed using mean differences (SD), Bland-Altman plots, correlation coefficients and ROC Area under the Curve (AUC) for a cut off of ≥100 mmol of Na/day. The Food Choice at Work study recruited 802 participants aged 18-64 years, 50 of whom formed the validation sample. The mean measured 24-h urinary sodium (gold standard) was 138 mmol/day (8.1 g salt). At the group level, mean differences were small for both dietary methods and for the arithmetic extrapolations from morning urine samples. The Tanaka, Kawasaki and INTERSALT methods provided biased estimates of 24-h urinary sodium. R(2) values for all methods ranged from 0.1 to 0.48 and AUC findings from 0.57 to 0.76. CONCLUSION: Neither dietary nor spot urine sample methods provide adequate validity in the estimation of 24-h urinary sodium at the individual level. However, group mean errors from dietary methods are small and random and compare favourably with those from spot urine samples in this population.

Short-term blood pressure variability over 24 h and target organ damage in middle-aged men and women.

Blood pressure variability (BPV) has been associated with cardiovascular events; however, the prognostic significance of short-term BPV remains uncertain. As uncertainty also remains as to which measure of variability most accurately describes short-term BPV, this study explores different indices and investigates their relationship with subclinical target organ damage (TOD). We used data from the Mitchelstown Study, a cross-sectional study of Irish adults aged 47-73 years (n=2047). A subsample (1207) underwent 24-h ambulatory BP monitoring (ABPM). As measures of short-term BPV, we estimated the s.d., weighted s.d. (wSD), coefficient of variation (CV) and average real variability (ARV). TOD was documented by microalbuminuria and electrocardiogram (ECG) left ventricular hypertrophy (LVH). There was no association found between any measure of BPV and LVH in both unadjusted and fully adjusted logistic regression models. Similar analysis found that ARV (24 h, day and night), s.d. (day and night) and wSD were all univariately associated with microalbuminuria and remained associated after adjustment for age, gender, smoking, body mass index (BMI), diabetes and antihypertensive treatment. However, when the models were further adjusted for the mean BP the association did not persist for all indices. Our findings illustrate choosing the appropriate summary measure, which accurately captures that short-term BPV is difficult. Despite discrepancies in values between the different measures, there was no association between any indexes of variability with TOD measures after adjustment for the mean BP.

Outcomes of a patient recall following early failure of hip hemiarthroplasty.

BACKGROUND: Unexpected early loosening was noted in some patients who had bipolar hemiarthroplasties using aspecific combination of head and stem. AIM: A review of all patients who had received this implant combination was performed to establish whether there was a higher than expected failure rate and to identify those patients who had evidence of early loosening requiring further intervention or monitoring. METHODS: Theatre records were reviewed to identify those who had undergone bipolar hemiarthroplasty using these products. All surviving patients were contacted and offered an appointment at which they underwent clinical and radiological review. Following review, revision rates were compared to published Australian joint registry data. RESULTS: Of 247 eligible for recall, 139 attended for clinical and radiological review. The cumulative revision rate was 6.8 % at 4 years, with a mean time to revision of 26 months; however, there was a significantly higher revision rate of 12.1 % in those aged under 75 years at the time of surgery (p = 0.01). This is significantly higher than rates quoted for bipolar hemiarthroplasties in Australian joint registry data. CONCLUSION: Overall, higher than expected revision rates due to early loosening were seen for this product combination,especially in patients aged\75 years at the time of the initial surgery.

Entry to medical school--the gender question. What has happened?

Reform of medical schooI selection has generated concerns that the process favours male applicants. The gender profile, HPAT-Ireland and Leaving Certificate scores of all applicants in 2009-2011 (n = 9582) and the gender profile of entrants from 2008-2011 is presented. Small gender differences favouring males are evident in total HPAT-Ireland scores and subsection scores less than 7 and 4 points respectively with a total selection score impact of approximately 0.8%. In relation to Leaving Certificate performance, since 2009, eligible male applicants to medicine have tended to outperform females with less than 3 points mean difference which has an impact close to 0.7% as selection is still weighted in favour of this test. The gender profile of applicants securing a place has varied annually. Reforms may have inadvertently altered the gender distribution in medical school but there is no evidence that this is entirely attributable to the HPAT-Ireland test.

Persistent lactic acidosis in neonatal hypoxic-ischaemic encephalopathy correlates with EEG grade and electrographic seizure burden.

BACKGROUND: Predicting at birth which infants with perinatal hypoxic-ischaemic injury will progress to significant encephalopathy remains a challenge. OBJECTIVE: To determine whether lactic acidosis at birth in asphyxiated neonates could predict the grade of EEG encephalopathy by examining the relationship between time taken for the normalisation of lactate, severity of encephalopathy and seizure burden. METHODS: Continuous early video-EEG monitoring was performed in babies at risk for hypoxic-ischaemic encephalopathy. Encephalopathy was graded from the EEG data. Total seizure burden (seconds) was calculated for each baby. Initial blood gas measurements of pH, base deficit and lactate were taken within 30 minutes of delivery. Time to normal serum lactate was determined in hours from birth for each infant. RESULTS: All 50 term infants had raised initial serum lactate (median (lower, upper quartiles) 11.7 (10.2, 14.9)). There were no significant differences between the initial serum lactate, pH and base deficit in infants with normal/mildly abnormal (n = 24), moderately abnormal (n = 14), severely abnormal (n = 5) and inactive EEGs (n = 7). Time to normal lactate varied significantly with EEG grade (median (lower, upper quartile) 6.0 (4.1, 9.5) for mild/normal EEG, 13.5 (6.8, 23.5) moderate EEG, 41.5 (30.0, 55.5) severe group, 12.0 (8.1, 21.5) inactive group; p<0.001). Time to normal lactate correlated significantly with EEG seizure burden (seconds; R = 0.446, p = 0.002). Mean (SD) time to normal lactate was 10.0 (7.2) hours in infants who did not have seizures and 27.3 (19.0) hours in the 13 infants with electrographic seizures (p = 0.002). CONCLUSIONS: Serum lactate levels in the first 30 minutes of life do not predict the severity of the ensuing encephalopathy. In contrast, sustained lactic acidosis is associated with severe encephalopathy on EEG and correlates with seizure burden.

Haplotypes in the CTLA4 region are associated with coeliac disease in the Irish population.

Chromosomal region 2q33 encodes the immune regulatory genes, CTLA4, ICOS and CD28, which are involved in regulation of T-cell activity and has been studied as a candidate gene locus in autoimmune diseases, including coeliac disease (CD). We have investigated whether an association exists between this region and CD in the Irish population using a comprehensive analysis for genetic variation. Using a haplotype-tagging approach, this gene cluster was investigated for disease association in a case-control study comprising 394 CD patients and 421 ethnically matched healthy controls. Several SNPs, including CTLA4_CT60, showed association with disease; however, after correction for multiple-testing, CTLA4-658C/T was the only polymorphism found to show significant association with disease when allele, genotype, or carrier status frequency were analysed (carrier status (Allele C), P = 0.0016). Haplotype analysis revealed a haplotype incorporating the CD28/CTLA4 and two 5' ICOS polymorphisms to be significantly associated with disease (patients 24.1%; controls 31.5%; P = 0.035), as was a shorter haplotype composed of the CTLA4 markers only (30.9 vs 34.9%; P = 0.042). The extended haplotype incorporating CD28/CTLA4 and 5' ICOS is more strongly associated with disease than haplotypes of individual genes. This suggests a causal variant associated with this haplotype may be associated with disease in this population.

Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project.

AIMS: The SCORE project was initiated to develop a risk scoring system for use in the clinical management of cardiovascular risk in European clinical practice. METHODS AND RESULTS: The project assembled a pool of datasets from 12 European cohort studies, mainly carried out in general population settings. There were 20,5178 persons (88,080 women and 11,7098 men) representing 2.7 million person years of follow-up. There were 7934 cardiovascular deaths, of which 5652 were deaths from coronary heart disease. Ten-year risk of fatal cardiovascular disease was calculated using a Weibull model in which age was used as a measure of exposure time to risk rather than as a risk factor. Separate estimation equations were calculated for coronary heart disease and for non-coronary cardiovascular disease. These were calculated for high-risk and low-risk regions of Europe. Two parallel estimation models were developed, one based on total cholesterol and the other on total cholesterol/HDL cholesterol ratio. The risk estimations are displayed graphically in simple risk charts. Predictive value of the risk charts was examined by applying them to persons aged 45-64; areas under ROC curves ranged from 0.71 to 0.84. CONCLUSIONS: The SCORE risk estimation system offers direct estimation of total fatal cardiovascular risk in a format suited to the constraints of clinical practice.

The contribution of genetic factors to thrombotic and bleeding outcomes in coronary patients randomised to IIb/IIIa antagonists.

Genetic variants are risk factors for coronary disease, but their role in recurrent events and in response to treatment is less clear. We genotyped genetic variants implicated in primary coronary disease in 924 Caucasians with acute coronary syndromes participating in the OPUS-TIMI16 trial of the GPIIb/IIIa antagonist orbofiban. These were the platelet glycoprotein (GP) receptors GPIIIa, GPIa, GPIbalpha; platelet ligands beta-fibrinogen and von Willebrand Factor (vWF); interleukins (IL) IL-1RN, and IL-6; adhesion proteins E-selectin and P-selectin; and metalloproteinase MMP-9. Cox modelling of all genetic variants demonstrated no significant impact on the composite endpoint (P = 0.88), which included myocardial infarction (MI), death, recurrent ischemia, urgent revascularisation and stroke, but a significant impact on recurrent myocardial infarction alone (chi(2) = 20.4, 10 df, P = 0.04). There was a significant interaction of the polymorphisms with orbofiban treatment influencing bleeding outcomes (P = 0.004). Thus, genetic polymorphisms may be associated with subsequent myocardial infarction, and may also be associated with treatment-associated bleeding among coronary patients.

Microalbuminuria and coronary heart disease in NIDDM: an incidence study.

In most survival studies in NIDDM, microalbuminuria (urinary albumin excretion rate 20-200 microg/min) predicts early mortality; in cross-sectional studies, it is associated with coronary heart disease (CHD) morbidity. It is unclear, however, whether microalbuminuria is a risk factor for the development of CHD or the result of it, and little is known of the factors that predispose to the development of microalbuminuria in NIDDM. We examined these issues in a 7-year prospective study of a hospital-based cohort comprising 146 white NIDDM patients without clinical albuminuria. Microalbuminuria was a significant risk factor for both all-cause mortality (relative risk 3.94, 95% CI 2.04-7.62) and CHD mortality (relative risk 7.40, 95% CI 2.94-18.7) when adjusted for age only. Its independent predictive power did not persist, however, in age-adjusted multivariable survival analysis that allowed for the other significant risk factors: male sex, preexisting CHD, high levels of glycated hemoglobin, and high serum cholesterol. Among men free of CHD at baseline, the independent risk factors for CHD morbidity and mortality were microalbuminuria, current smoking, high diastolic blood pressure, and high serum cholesterol (all P < 0.05). For the 100 NIDDM patients with normoalbuminuria at baseline, the incidence of microalbuminuria was 29% over the 7-year period. In that group, fasting plasma glucose, current smoking, preexisting CHD, and high initial urinary albumin excretion rate were risk factors for the development of microalbuminuria (all P < 0.05). When men and women were analyzed separately, preexisting CHD was a significant risk factor in men only. These results demonstrate that microalbuminuria predicts incident clinical CHD in men with NIDDM. Preexisting CHD is also a risk factor for incident microalbuminuria in men, however, suggesting that microalbuminuria and CHD are not causally related but rather reflect common determinants.

Serum sialic acid concentration and coronary heart disease in NIDDM.

OBJECTIVE--To examine the association between serum sialic acid concentrations and coronary heart disease (CHD) in a cross-sectional study of non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS--NIDDM patients (n = 145) attending a diabetic clinic were studied. CHD status was assessed by questionnaire and electrocardiogram coding, and potential risk factor assessment included measurement of fasting serum lipid and lipoprotein concentrations, blood pressure, and urinary albumin excretion rate (AER). RESULTS--Male NIDDM patients with CHD had a higher serum sialic acid level than those without CHD: 2.56 (2.24, 2.72) mmol/l vs. 2.24 (2.18, 2.30) mmol/l, P = 0.01, mean (95% confidence interval). They were also older, had a longer duration of diabetes, had a higher AER, had higher total triglyceride, very-low-density lipoprotein triglyceride and cholesterol, and lipoprotein(a) concentrations, and had a lower apolipoprotein A1 concentration. In an age adjusted multiple lipoprotein(a), hypercholesterolemia, and hypertension were associated with CHD. In women, only hypertension treatment was associated with CHD. CONCLUSIONS--There is a strong univariate association between elevated serum sialic acid and CHD in men (but not women) with NIDDM.

Heaven can wait.

The apparently unlimited demand for health care, finite supply of resources, the internal social market and continuous technological advances have given rise to increasing concern about the performance of health services. We examine an important measure of health care performance--avoidable mortality. Studies extending the scope of avoidable mortality and other outcome indicators are discussed. Although avoidable mortality is limited to providing a warning signal of possible health care deficiencies and is not an appropriate measure for all types of intervention, it still provides us with one of the best guides to the performance of health services.

Prospective study of microalbuminuria as predictor of mortality in NIDDM.

Retrospective studies of patients with non-insulin-dependent diabetes mellitus (NIDDM) have suggested that microalbuminuria predicts early all-cause (mainly cardiovascular) mortality independently of arterial blood pressure. These findings have not been confirmed in prospective studies, and it is not known whether the predictive power of microalbuminuria is independent of other major cardiovascular risk factors. During 1985-1987, we examined a representative group of 141 nonproteinuric patients with NIDDM for the prevalence of coronary heart disease and several of its established and putative risk factors, including raised urinary albumin excretion (UAE) rate. Thirty-six patients had microalbuminuria (UAE 20-200 micrograms/min), and 105 had normal UAE (less than 20 micrograms/min). At follow-up, an average of 3.4 yr later, 14 patients had died. There was a highly significant excess mortality (chiefly from cardiovascular disease) among those with microalbuminuria (28%) compared to those without microalbuminuria (4%, P less than 0.001). In univariate survival analysis, significant predictors of all-cause mortality included microalbuminuria (P less than 0.001), hypercholesterolemia (P less than 0.01), hypertriglyceridemia (P less than 0.05), and preexisting coronary heart disease (P less than 0.05). The predictive power of microalbuminuria persisted after adjustment for the effects of other major risk factors (P less than 0.05). We conclude that microalbuminuria is a significant risk marker for mortality in NIDDM, independent of the other risk factors examined. Its presence can be regarded as an index of increased cardiovascular vulnerability and a signal for vigorous efforts at correction of known risk factors.