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Background Reliable statistics on the underlying cause of death are essential for monitoring the health in a population. When there is insufficient information to identify the true underlying cause of death, the death will be classified using less informative codes, garbage codes. If many deaths are assigned a garbage code, the information value of the cause-of-death statistics is reduced. The aim of this study was to analyse the use of garbage codes in the Norwegian Cause of Death Registry (NCoDR). Methods Data from NCoDR on all deaths among Norwegian residents in the years 1996–2019 were used to describe the occurrence of garbage codes. We used logistic regression analyses to identify determinants for the use of garbage codes. Possible explanatory factors were year of death, sex, age of death, place of death and whether an autopsy was performed. Results A total of 29.0% (290,469/1,000,128) of the deaths were coded with a garbage code; 14.1% (140,804/1,000,128) with a major and 15.0% (149,665/1,000,128) with a minor garbage code. The five most common major garbage codes overall were ICD-10 codes I50 (heart failure), R96 (sudden death), R54 (senility), X59 (exposure to unspecified factor), and A41 (other sepsis). The most prevalent minor garbage codes were I64 (unspecified stroke), J18 (unspecified pneumonia), C80 (malignant neoplasm with unknown primary site), E14 (unspecified diabetes mellitus), and I69 (sequelae of cerebrovascular disease). The most important determinants for the use of garbage codes were the age of the deceased (OR 17.4 for age ≥ 90 vs age < 1) and death outside hospital (OR 2.08 for unknown place of death vs hospital). Conclusion Over a 24-year period, garbage codes were used in 29.0% of all deaths. The most important determinants of a death to be assigned a garbage code were advanced age and place of death outside hospital. Knowledge of the national epidemiological situation, as well as the rules and guidelines for mortality coding, is essential for understanding the prevalence and distribution of garbage codes, in order to rely on vital statistics.

Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about possible cancer risks. We aimed to assess any effects on site-specific cancer rates in the randomised trials of folic acid supplementation, at doses higher than those from fortification. In these meta-analyses, we sought all trials completed before 2011 that compared folic acid versus placebo, had scheduled treatment duration at least 1 year, included at least 500 participants, and recorded data on cancer incidence. We obtained individual participant datasets that included 49 621 participants in all 13 such trials (ten trials of folic acid for prevention of cardiovascular disease [n=46 969] and three trials in patients with colorectal adenoma [n=2652]). All these trials were evenly randomised. The main outcome was incident cancer (ignoring non-melanoma skin cancer) during the scheduled treatment period (among participants who were still free of cancer). We compared those allocated folic acid with those allocated placebo, and used log-rank analyses to calculate the cancer incidence rate ratio (RR). During a weighted average scheduled treatment duration of 5·2 years, allocation to folic acid quadrupled plasma concentrations of folic acid (57·3 nmol/L for the folic acid groups vs 13·5 nmol/L for the placebo groups), but had no significant effect on overall cancer incidence (1904 cancers in the folic acid groups vs 1809 cancers in the placebo groups, RR 1·06, 95% CI 0·99–1·13, p=0·10). There was no trend towards greater effect with longer treatment. There was no significant heterogeneity between the results of the 13 individual trials (p=0·23), or between the two overall results in the cadiovascular prevention trials and the adenoma trials (p=0·13). Moreover, there was no significant effect of folic acid supplementation on the incidence of cancer of the large intestine, prostate, lung, breast, or any other specific site. Folic acid supplementation does not substantially increase or decrease incidence of site-specific cancer during the first 5 years of treatment. Fortification of flour and other cereal products involves doses of folic acid that are, on average, an order of magnitude smaller than the doses used in these trials. British Heart Foundation, Medical Research Council, Cancer Research UK, Food Standards Agency.

Increasing differences in cardiovascular disease (CVD) mortality across levels of education have been reported in Norway. The aim of the study was to investigate educational inequalities in acute myocardial infarction (AMI) incidence and whether such inequalities have changed during the past decade using a nationwide longitudinal study design. Data on 141 332 incident (first) AMIs in Norway during 2001-2009 were obtained through the Cardiovascular Disease in Norway (CVDNOR) project. Educational inequalities in AMI incidence were assessed in terms of age-standardised incidence rates stratified on educational level, incidence rate ratios (IRR), relative index of inequality (RII) and slope index of inequality (SII). All calculations were conducted in four gender and age strata: Men and women aged 35-69 and 70-94 years. AMI Incidence rates decreased during 2001-2009 for all educational levels except in women aged 35-69 among whom only those with basic education had a significant decrease. In all gender and age groups; those with the highest educational level had the lowest rates. The strongest relative difference was found among women aged 35-69, with IRR (95% CI) for basic versus tertiary education 3.04 (2.85-3.24)) and RII (95% CI) equal to 4.36 (4.03-4.71). The relative differences did not change during 2001-2009 in any of the four gender and age groups, but absolute inequalities measured as SII decreased among the oldest men and women. There are substantial educational inequalities in AMI incidence in Norway, especially for women aged 35-69. Relative inequalities did not change from 2001 to 2009.

Background For injury deaths, the underlying cause of death is defined as the circumstances leading to the injury. When this information is missing, the ICD-10 code X59 (Exposure to unspecified factor) is used. Lack of knowledge of factors causing injuries reduces the value of the cause of death statistics. The aim of this study was to identify predictors of X59-coded deaths in Norway, and to assess methods to identify the true underlying cause of injury deaths. Methods We used data from the Norwegian Cause of Death Registry from 2005 to 2014. We used logistic regression to identify determinants of X59-coded deaths. For redistribution of the X59 deaths, we used a multinomial logistic regression model based on the cases where injury circumstances were known. The data were divided into training and test sets. The model was developed on the training set and assessed on the test set before it was applied to the X59 deaths. The models used death certificate information on the nature of injury and demographic characteristics as predictor variables. Furthermore, we mailed a query to the certifying physicians of X59 deaths reported in the year 2015, where we asked for additional information on the circumstances leading to the fatal injury. Results There were 24,963 injury deaths reported to the Cause of Death Registry of Norway 2005–2014. Of these, 6440 (25.8%) lacked information on the circumstances leading to the death. The strongest predictor for a X59 death was the nature of injury (hip fracture), followed by lack of information on the scene of injury. Applying our redistribution algorithm, we estimated that 97% of the X59-coded deaths were accidental falls. The strongest covariate was the nature of injury, followed by place of death and age at death. In 2015, there were 591 X59-coded deaths. Queries were sent to the certifying doctors in 559 cases. Among the informative replies to the query, 88% of the deaths were reclassified to accidental falls. Conclusions A large proportion of injury deaths in Norway lack information on the circumstances leading to the fatal injury. Typically, these deaths represent accidental falls causing hip fracture in elderly individuals.

We explored trends in acute myocardial infarction (AMI) event rates in Norway during 1994 to 2009 and trends in the 6-month, 1-year, and 3-year risk of recurrences after an incident AMI during 2001 to 2008 in men and women ≥25 years. Trends in AMI event rates (incident and recurrent) were analyzed using joinpoint regression analyses and expressed as annual percentage change (APC) in rates. Trends in AMI recurrences were explored using conditional risk models for ordered events in Cox regression. Analyses were stratified by gender and age group. Overall, AMI rates were stable during 1994 to 2002 but declined during 2002 to 2009 (APC = −2.0; 95% confidence interval [CI] −3.1 to −0.9 in men; APC = −2.1; 95% CI −3.8 to −0.5 in women). In the younger age group, rates declined during the whole study period in men (APC = −0.6; 95% CI −1.0 to −0.3) but not in women. Among older patients, no changes were observed during 1994 to 2002, whereas rates declined during 2002 to 2009 (APC = −2.6; 95% CI −3.8 to −1.4 in men; APC = −2.4; 95% CI −4.0 to −0.7 in women). During 2001 to 2008, in the older age group, the 6-month, 1-year, and 3-year risks of recurrences were reduced annually by 4.7%, 4.3%, and 5.4% in men and 5.2%, 5.0%, and 5.7% in women (all ptrend <0.001), respectively. No changes were observed in the younger age group. In conclusion, favorable trends in AMI event rates and recurrences observed in Norway were mostly seen among patients aged 65+ years, whereas less favorable trends were observed among younger patients, especially among women.

Abnormal urinary excretion of betaine has been demonstrated in patients with diabetes or metabolic syndrome. We aimed to identify the main predictors of excretion in cardiovascular patients and to make initial assessment of its feasibility as a risk marker of future diabetes development. We used data from 2396 patients participating in the Western Norway B-vitamin Intervention Trial, who delivered urine and blood samples at baseline, and in the majority at two visits during follow-up of median 39 months. Betaine in urine and plasma were measured by liquid-chromatography-tandem mass spectrometry. The strongest determinants of urinary betaine excretion by multiple regression were diabetes mellitus, age and estimated glomerular filtration rate; all p<0.001. Patients with diabetes mellitus (n = 264) had a median excretion more than three times higher than those without. We found a distinct non-linear association between urinary betaine excretion and glycated hemoglobin, with a break-point at 6.5%, and glycated hemoglobin was the strongest determinant of betaine excretion in patients with diabetes mellitus. The discriminatory power for diabetes mellitus corresponded to an area under the curve by receiver-operating characteristics of 0.82, and betaine excretion had a coefficient of reliability of 0.73. We also found a significant, independent log-linear relation between baseline betaine excretion and the risk of developing new diabetes during follow-up. The good discriminatory power for diabetes, high test-retest stability and independent association with future risk of new diabetes should motivate further investigation on the role of betaine excretion in risk assessment and long-term follow-up of diabetes mellitus.

Loop diuretics are widely used in patients with heart and renal failure, as well as to treat hypertension and peripheral edema. However, there are no randomized, controlled trials (RCT) evaluating their long term safety, and several observational reports have indicated adverse effects. We sought to evaluate the impact of loop diuretics on long term survival in patients with suspected coronary artery disease, but without clinical heart failure, reduced left ventricular ejection fraction or impaired renal function. From 3101 patients undergoing coronary angiography for suspected stable angina pectoris, subjects taking loop diuretics (n=109) were matched with controls (n=198) in an attempted 1:2 ratio, using propensity scores based on 59 baseline variables. During median follow-up of 10.1 years, 37.6% in the loop diuretics group and 23.7% in the control group died (log-rank p-value 0.005). Treatment with loop diuretics was associated with a hazard ratio (95% confidence interval) of 1.82 (1.20, 2.76), and the number needed to harm was 7.2 (4.1, 30.3). Inclusion of all 3101 patients using propensity score weighting and adjustment for numerous covariates provided similar estimates. The main limitation is the potential of confounding from unmeasured patient characteristics. The use of loop diuretics in patients with suspected coronary artery disease, but without systolic heart failure or renal impairment, is associated with increased risk of all-cause mortality. Considering the lack of randomized controlled trials to evaluate long term safety of loop diuretics, our data suggest caution when prescribing these drugs to patients without a clear indication.

Background: Smoking is associated with decreased concentrations of several antioxidant vitamins. We sought to determine the relation between circulating concentrations of selected B vitamins and smoking status, with particular attention to longitudinal associations. Methods: We used baseline data from 2 B-vitamin intervention trials that included 6837 patients with ischemic heart disease. Smoking habits were ascertained by interview. Vitamins and metabolites, including the nicotine metabolite cotinine, were measured in plasma and serum by microbiological assays or gas/liquid chromatography–tandem mass spectrometry. Results: The highest circulating concentrations of folate and pyridoxal 5′phosphate (PLP) and lowest concentrations of total plasma homocysteine, a functional marker of folate status, were observed for self-reported never smokers, followed by self-reported ex-smokers and current smokers (Ptrend < 0.001). Cobalamin and its functional marker methylmalonic acid were not associated with smoking status. Based on their low cotinine concentrations, we were able to identify a group of smokers that had abstained from smoking for 3 days or more. Compared with smokers with high plasma cotinine, smokers with low cotinine had significantly higher circulating concentrations of folate, PLP, and riboflavin (all P < 0.005), and this trend continued for ex-smokers, with increasing time since smoking cessation. Conclusions: Smoking lowered circulating concentrations of folate, PLP, and riboflavin, but concentrations increased significantly after a few days of smoking cessation. We propose that short-term effects may be related to acute smoking-induced oxidative stress, whereas the longer-lasting effects among ex-smokers may reflect changes in diet and/or restoration of vitamin concentrations in tissue during the first few months to years after smoking cessation.

Aims: Health registers are used for administrative purposes, disease surveillance, quality assessment, and research. The value of the registers is entirely dependent on the quality of their data. The aim of this study was to investigate and compare the completeness and correctness of the acute myocardial infarction (AMI) diagnosis in the Norwegian Myocardial Infarction Register and in the Norwegian Patient Register. Methods: All Norwegian patients admitted directly to St Olavs hospital, Trondheim University Hospital, Trondheim University Hospital from 1 July to 31 December 2012 and who had plasma levels of cardiac troponin T measured during their hospitalization (n=4835 unique individuals, n=5882 hospitalizations) were identified in the hospital biochemical database. A gold standard for AMI was established by evaluation of maximum troponin T levels and by review of the information in the medical records. Cases of AMI in the registers were classified as true positive, false positive, true negative, and false negative according to the gold standard. We calculated sensitivity, positive predictive value (PPV), specificity, and negative predictive value (NPV). Results: The Norwegian Myocardial Infarction Register had a sensitivity of 86.0% (95% confidence interval (CI) 82.8–89.3%), PPV of 97.9% (96.4–99.3%), and specificity of 99.9% and NPV of 98.9% (98.6-99.2%) (99.8–100%). The corresponding figures for the Norwegian Patient Register were 85.8% (95% CI 82.5–89.1%), 95.1% (92.9–97.2%), and 99.7% (99.5–99.8%) and 98.9% (98.6-99.2%), respectively. Both registers had a sensitivity higher than 95% when compared to hospital discharge diagnoses. The results were similar for men and women and for cases below and above 80 years of age. Conclusions: The Norwegian Myocardial Infarction Register and the Norwegian Patient Register are adequately complete and correct for administrative purposes, disease surveillance, quality assessment, and research.

Aims: Health registers are essential sources of data used in a wide range of stroke research, including epidemiological, clinical and healthcare studies. Regardless of the type of register, the data must be of high quality to be useful. In this study, we investigated and compared the correctness and completeness of the Norwegian Patient Register (an administrative health register) and the Norwegian Stroke Register (a medical quality register for acute stroke). Methods: We reviewed the medical records for 5192 admissions to hospital in 2012 and defined cases of stroke in the two registers as true positive, false positive, true negative or false negative. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value with 95% confidence intervals assuming a normal approximation of the binomial distribution. Results: The Norwegian Stroke Register was highly correct and relatively complete (sensitivity 88.1%, specificity 100% and PPV 98.6%). The Norwegian Patient Register was more complete, but less correct, when we included both the main and secondary diagnoses of stroke (sensitivity 96.8%, specificity 99.6% and PPV 79.7%); restricting the analyses to the main diagnoses of stroke resulted in less complete and more correct registrations (sensitivity 86.1%, specificity 99.9% and PPV 93.5%). Conclusions: The Norwegian Stroke Register and the Norwegian Patient Register are adequately complete and correct to serve as valuable sources of data for epidemiological, clinical and healthcare studies, as well as for administrative purposes.