Medication error with methotrexate. / Feildosering av metotreksat.

Background: A woman in her seventies presented to the accident and emergency department (A&E) with shortness of breath that had increased over a period of three weeks. She had a history of COPD, hypertension and polymyalgia rheumatica. A medication error involving methotrexate, used for autoimmune diseases, was discovered during her medical history review. Case presentation: The patient arrived with stable vital signs, including 94 % oxygen saturation and a respiratory rate of 20 breaths/min. She had been taking 2.5 mg of methotrexate daily for the past three weeks instead of the prescribed weekly dose of 15 mg. Other examinations revealed no alarming findings, except for a slightly elevated D-dimer level. Interpretation: Considering her medical history and exclusion of other differential diagnoses, methotrexate toxicity was suspected. The patient was admitted to the hospital and intravenous folinic acid was initiated as an antidote treatment. Five days later, the patient was discharged with an improvement in the shortness of breath. This case underscores the importance of effective communication in health care, particularly in complex cases like this, where understanding dosages and administration is crucial. Medical history, clinical examinations and medication reviews, often involving clinical pharmacists, are vital in the A&E to reveal medication errors.

Insomnia symptoms and risk for atrial fibrillation - The HUNT study.

Studies on the effect of insomnia on atrial fibrillation risk in the general population are limited, therefore we investigated the association between insomnia and the risk of atrial fibrillation in a large-scale population-based study with valid atrial fibrillation measure. A total of 33,983 participants (55% women) reported their insomnia symptoms in the third wave of the HUNT study (between 2006 and 2008) in Norway, and they were followed for their first atrial fibrillation diagnosis until 2020 using hospital registers. Atrial fibrillation diagnoses were validated by physicians based on medical records and electrocardiograms. Insomnia symptoms were assessed by four questions, and analysed both individually and as cumulative symptoms. Cox regression, adjusted for age, sex, social and marital status, working in shiftwork, alcohol consumption, smoking, physical activity, body mass index, systolic blood pressure, and symptoms of anxiety and depression, was conducted. Overall, 1592 atrial fibrillation cases were identified during the follow-up and 31.6% of individuals reported at least one insomnia symptom. In our analysis, we did not detect meaningful associations between insomnia symptoms and the risk of atrial fibrillation. In conclusion, in this population there was no evidence for an association between insomnia symptoms and the risk of subsequent atrial fibrillation.

Development of a tool to predict the risk of incident heart failure in a general population: the HUNT for HF risk score.

AIMS: Currently, no incident heart failure (HF) risk score that is in regular use in a general population is available. We aimed to develop this and compare with existing HF risk scores. METHODS AND RESULTS: Participants in the third wave (2006-08) of the population-based Trøndelag Health Study 3 (HUNT3) were included if they reported no previous HF. Any hospital diagnoses captured during follow-up (until the end of 2018) of HF, cardiomyopathy, or hypertensive heart disease were assessed by an experienced cardiologist. Valid HF events were defined as symptoms/signs of HF and objective evidence of structural/functional abnormality of the heart at rest. The model was compared with slightly modified HF risk scores (the Health Aging and Body Composition HF risk score, the Framingham HF risk score, the Pooled Cohort equations to Prevent HF risk score, and NORRISK 2). Among 36 511 participants (mean ± SD age of 57.9 ± 13.3 years, 55.4% female), with a mean follow-up of 10.2 ± 1.3 years, 1366 developed HF (incidence rate of 3.66 per 1000 participant years). Out of the 38 relevant clinical variables assessed, we identified 12 (atrial fibrillation being the strongest) that independently predicted an HF event. The final model demonstrated good discrimination (C statistics = 0.904) and calibration, was stable in internal validation, and performed well compared with existing risk scores. The model identified that, at enrolment, 31 391 (86%), 2386 (7%), 1246 (3%), and 1488 (4%) had low, low-intermediate, high-intermediate, and high 10-year HF risk, respectively. CONCLUSIONS: Twelve clinical variables independently predicted 10-year HF risk. The model may serve well as the foundation of a practical, online risk score for HF in general practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04648852.

Anxiety and depression symptoms, albuminuria and risk of acute myocardial infarction in the Norwegian HUNT cohort study.

BACKGROUND: Studies suggest increased risk for an outcome in people with joint exposures that share common causal pathways. The objective of this study was to determine the risk of incident acute myocardial infarction (AMI) following exposure to both albuminuria and/or anxiety and depression symptoms. METHODS: Participants who provided urine samples to the HUNT2 (1995-97) or HUNT3 (2007-2009) surveys were followed until the end of 2016. Albuminuria was measured by Albumin Creatine Ratio (ACR) and participants self-reported mood and anxiety symptoms on the Hospital Anxiety and Depression scale. We used Cox regression to estimate hazard ratios (HRs) for first incident AMI considering interaction between exposures and additive models to calculate the proportion of AMI that were attributable to the synergy of both exposures, adjusted for the Framingham variables. RESULTS: Eleven thousand fourteen participants free of previous AMI were eligible for participation, with 1234 incident AMIs occurred during a mean 13.7 years of follow-up. For participants who had a healthier CVD risk profile, the HR for AMI of having both albuminuria (3-30 mg/mmol) and depression (≥8) was 2.62 (95% 1.12-6.05) compared with a HR 1.34 (95% CI 1.04-1.74) with raised ACR only (Likelihood Ratio-test 0.03). Adding anxiety (≥8) to albuminuria (3-30) tripled the risk (HR 3.32 95% CI 1.43-7.17). The additive models suggest that these risks are not higher than expected based on each risk factor alone. CONCLUSIONS: This study indicate that the risk of AMI in persons with elevated albuminuria but with an otherwise healthy CVD profile might be amplified by anxiety and depression symptoms. The increased risk with joint risk factors is not higher than expected based on each risk factor alone, which indicate that the risk factors do not share causal pathways.

Observational study on chest pain during the Covid-19 pandemic: changes and characteristics of visits to a Norwegian emergency department during the lockdown.

BACKGROUND: Following the spread of the Covid-19 pandemic in 2020, reports emerged on decreasing emergency department (ED) visits in many countries. Patients experiencing chest pain was no exception. The aim of the current study was to describe how the Covid-19 pandemic and the subsequential lockdown impacted the chest pain population in a Norwegian ED. METHODS: All patients presenting to the ED with chest pain during the study period were included. Data were collected retrospectively from the time period January 6th to August 30th, 2020, and compared to the corresponding period in 2019, assessing variations in the number of ED visits, severity, gender, and age. RESULTS: Fewer patients with chest pain were seen in the ED following the national lockdown in Norway, compared to the corresponding 2019 period (week 13: 38% fewer; weeks 11-27: 16% fewer). By week 28, the rate normalized compared to 2019 levels. There was a relative increase in lower acuity patients among these patients, while fewer moderate acuity patients were seen. During the initial period following lockdown, the median age was lower compared to the corresponding 2019 period (58 years (IQR 25) vs 62 years (IQR 24), respectively). Admissions due to acute coronary syndromes (ACS) remained proportionally stable. CONCLUSIONS: Succeeding the Covid-19 outbreak and the subsequent national lockdown in Norway, fewer chest pain patients presented to the ED. Paradoxically, the patients seemed to be less severely ill and were on average younger compared to 2019 data. However, the proportion of patients admitted with ACS was stable during this period. This could imply that some patients may have failed to seek medical advice despite experiencing a myocardial infarction.

Patient visits to an emergency department in anticipation of the COVID-19 pandemic. / Pasienttilstrømming i et akuttmottak i påvente av covid-19-pandemien.

BACKGROUND: The Emergency Department in Trondheim has prepared for a large influx of patients infected with the SARS-CoV-2 virus. We conducted a study comparing patients in the Emergency Department in the first weeks of the pandemic in Norway (weeks 11 and 12) with the average number of patient visits. MATERIAL AND METHOD: Data from patients at the Emergency Department of St Olav's Hospital in the period 6 January 2020-22 March 2020 were retrieved from the Emergency Department's database. Logistical patient data concerning patient numbers, chief complaints, length of stay in the Emergency Department, acuity level, isolation status, and treatment level were analysed. RESULTS: In week 12, 331 patients were referred to the Emergency Department, a reduction of 39 % compared with the average of 541 patients in weeks 2-10. There was a general reduction in all patient groups, but particularly those discharged from the Emergency Department. In week 12 there were 56 more patients isolated with suspected/potentially infectious disease (187 %) compared with the average for weeks 2-10, and these patients spent almost two hours longer in the Emergency Department than other patients. INTERPRETATION: There was a reduction in patient visits to the Emergency Department in the first weeks of the pandemic. The percentage of patients isolated for infection control increased, and the time spent in the Emergency Department for these patients was greater than for other patients. The reduction in the inflow of patients is expected to be temporary, and the Emergency Department at St Olav's Hospital expects a large influx of patients with suspected COVID-19 disease.

Establishing the 99th percentile of a novel assay for high-sensitivity troponin I in a healthy blood donor population.

Background: The recommended cut-off of cardiac troponin (cTn) for the diagnosis of acute myocardial infarction (AMI) is the 99th percentile in a healthy reference population. We aimed to determine the 99th percentile of the novel ADVIA Centaur® High Sensitivity Troponin I assay (Siemens Healthcare Diagnostics) in fresh lithium heparin plasma samples from healthy blood donors. Methods: A total of 1000 apparently healthy blood donors were included. High-sensitivity (hs) cTnI, hs-cTnT, creatinine and N-terminal pro b-type natriuretic peptide (NT-proBNP) were measured in fresh lithium heparin plasma samples, and glycated hemoglobin (HbA1c) was measured in ethylenediaminetetraacetic acid (EDTA)-blood. The 99th percentile was estimated for the whole population, as well as for males and females separately. Results: For the total population the 99th percentile of ADVIA Centaur® High Sensitivity Troponin I was 96 (65-149) ng/L. The estimated value differed significantly from results published by others and was highly dependent on which values were considered statistical outliers. Conclusions: The estimated 99th percentile for hs-cTnI in the population studied differed significantly from previously published results. There is a need for further specifications regarding how subjects used for estimating the 99th percentile of cTns in healthy populations should be recruited and how outlier values should be identified, as this can highly influence the diagnostic cut-off applied for AMI.

Does Moderate Drinking Increase the Risk of Atrial Fibrillation? The Norwegian HUNT (Nord-Trøndelag Health) Study.

BACKGROUND: Compelling evidence suggests that excessive alcohol consumption increases the risk of atrial fibrillation (AF), but the effect of light-moderate alcohol consumption is less certain. We investigated the association between alcohol consumption within recommended limits and AF risk in a light-drinking population. METHODS AND RESULTS: Among 47 002 participants with information on alcohol consumption in a population-based cohort study in Norway, conducted from October 2006 to June 2008, 1697 validated AF diagnoses were registered during the 8 years of follow-up. We used Cox proportional hazard models with fractional polynomials to analyze the association between alcohol intake and AF. Population attributable risk for drinking within the recommended limit (ie, at most 1 drink per day for women and 2 drinks per day for men without risky drinking) compared with nondrinking was also calculated. The average alcohol intake was 3.8±4.8 g/d. The adjusted hazard ratio for AF was 1.38 (95% confidence interval, 1.06-1.80) when we compared participants consuming >7 drinks per week with abstainers. When we modeled the quantity of alcohol intake as a continuous variable, the risk increased in a curvilinear manner. It was higher with heavier alcohol intake, but there was virtually no association at <1 drink per day for women and <2 drinks per day for men in the absence of risky drinking. The population attributable risk among nonrisky drinkers was 0.07% (95% confidence interval, -0.01% to 0.13%). CONCLUSIONS: Although alcohol consumption was associated with a curvilinearly increasing risk of AF in general, the attributable risk of alcohol consumption within recommended limits among participants without binge or problem drinking was negligible in this population.

Prospective study of insomnia and incident asthma in adults: the HUNT study.

Insomnia is highly prevalent among asthmatics; however, few studies have investigated insomnia symptoms and asthma development. We aimed to investigate the association between insomnia and the risk of incident asthma in a population-based cohort.Among 17 927 participants free from asthma at baseline we calculated odds ratios and 95% confidence intervals for the risk of incident asthma among those with insomnia compared to those without. Participants reported sleep initiation problems, sleep maintenance problems and nonrestorative sleep. Chronic insomnia was defined as those reporting one or more insomnia symptom at baseline and 10 years earlier. Incident asthma was defined by questions on asthma at baseline and follow-up (average 11 years).The prevalence of sleep initiation problems, sleep maintenance problems and nonrestorative sleep were 1%, 1% and 5%, respectively. The multi-adjusted odds ratios were 1.18 (95% CI 0.97-1.44), 1.30 (95% CI 1.03-1.64) and 1.70 (95% CI 1.37-2.11) for people with one, two and three insomnia symptoms, respectively, compared with people without symptoms (p<0.01 for trend). The risk of developing asthma in those with chronic insomnia was three times higher (adjusted OR 3.16, 95% CI 1.37-6.40) than those without.Insomnia symptoms were associated with increased risk of incident asthma in this study.

Insomnia and the Risk of Breast Cancer: The HUNT Study.

OBJECTIVE: The association of insomnia with subsequent breast cancer risk is largely unknown. Therefore, we assessed whether different symptoms of insomnia and their combination are associated with incident breast cancer in a large population-based study. METHODS: In a prospective cohort study, 33,332 women were followed to monitor the occurrence of their first invasive breast cancer identified by the Cancer Registry of Norway. Insomnia symptoms including () nonrestorative sleep and () difficulty initiating and () maintaining sleep were self-reported using a study specific measure reflecting the current Diagnostic and Statistical Manual of Mental Disorders criteria. Hazard ratios and 95% confidence intervals were calculated using multiadjusted Cox proportional hazards models. RESULTS: A total of 862 incident breast cancer cases occurred during a mean follow-up of 14.7 years. No consistent association was observed between the individual insomnia symptoms and breast cancer risk. However, compared to women reporting no insomnia complaints, those who reported having all three aspects of insomnia simultaneously were at increased risk (hazard ratio, 2.38; 95% confidence interval = 1.11-5.09). CONCLUSION: Our results suggest that having only some aspects of insomnia may not predispose someone to breast cancer. In contrast, experiencing all insomnia symptoms simultaneously might confer considerable excess risk.

Genetic variants in the DNA repair gene NEIL3 and the risk of myocardial infarction in a nested case-control study. The HUNT Study.

BACKGROUND: Enhanced generation of reactive oxygen species and increased oxidative-induced DNA damage have been identified as possible contributors to atherosclerosis. The base excision repair (BER) pathway is the principal mechanism by which mammalian cells repair oxidative DNA damage. BER deficiency can potentially accelerate atherogenesis. METHODS: We evaluated the association of Single Nucleotide Polymorphisms (SNPs) in genes encoding four different BER proteins (NEIL3, OGG1, APEX1 and XRCC1) with the incidence of myocardial infarction in a nested case-control study among participants of the second survey of the HUNT Study. The study population included 1624 cases and 4087 age- and sex-matched controls. RESULTS: For the NEIL3 SNP rs12645561, the TT genotype was associated with increased risk of MI (OR 1.47, 95% CI 1.02-2.12, p uncorrected for multiple comparisons = 0.04) both in the genotypic test (compared to the CC genotype) and in the recessive genetic model (compared to the CC and CT genotypes combined). For the other two NEIL3 SNPs (rs10013040 and rs1395479) and for the SNPs of OGG1 (rs1052133), APEX1 (rs1878703) and XRCC1 (rs25489) we observed no association with risk of myocardial infarction. CONCLUSION: We found that the NEIL3 rs12645561 SNP TT genotype was associated with increased risk of myocardial infarction. If confirmed in other studies, this association may suggest a possible role of attenuated DNA repair, and NEIL3 in particular, in atherogenesis.

Insomnia symptoms and risk for unintentional fatal injuries--the HUNT Study.

STUDY OBJECTIVES: To assess the association between insomnia symptoms and risk of fatal unintentional injuries. DESIGN: Population-based prospective cohort study with a mean follow-up of 14 y, linking health survey data with information on insomnia symptoms to the National Cause of Death Registry. SETTING: Nord-Trøndelag County, Norway. PARTICIPANTS: A total of 54,399 men and women 20-89 y of age who participated in the Nord-Trøndelag Health Study between 1995 and 1997. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: There were 277 unintentional fatal injuries, including 57 fatal motor vehicle injuries during follow-up. There was a dose-dependent association between the number of insomnia symptoms and risk of unintentional fatal injuries (P for trend 0.001) and fatal motor vehicle injuries (P for trend 0.023), respectively. The proportion of unintentional fatal injuries cases that could have been prevented in the absence of difficulties initiating sleep, difficulties maintaining sleep, and having a feeling of nonrestorative sleep were 8%, 9%, and 8%, respectively. The corresponding estimates for motor vehicle injuries were 34%, 11%, and 10%. CONCLUSION: Insomnia is a major contributor to both unintentional fatal injuries in general as well as fatal motor vehicle injuries. Increasing public health awareness about insomnia and identifying persons with insomnia may be important in preventing unintentional fatal injuries.

Symptoms of anxiety and depression and risk of acute myocardial infarction: the HUNT 2 study.

AIMS: The nature of the association of depression and anxiety with risk for acute myocardial infarction (AMI) remains unclear. We aimed to study the prospective association of single and recurrent self-reported symptoms of anxiety and depression with a risk of AMI in a large Norwegian population based cohort. METHODS AND RESULTS: In the second wave of the Nord-Trøndelag Health Study (HUNT2, 1995-97) baseline data on anxiety and depression symptoms, sociodemographic variables, health status including cardiovascular risk factors and common chronic disorders were registered for 57,953 adult men and women free of cardiovascular disease. The cohort was followed up during a mean (SD) 11.4 (2.9) years for a first AMI from baseline through 2008. A total of 2111 incident AMIs occurred, either identified at hospitals or by the National Cause of Death Registry. The multi-adjusted hazard ratios were 1.31 (95% CI 1.03-1.66) for symptoms of depression and 1.25 (CI 0.99-1.57) for anxiety. Two episodes of mixed symptoms of anxiety and depression (MSAD), reported 10 years apart, increased the risk for AMI by 52% (11-108%). After exclusion of the first 5 years of follow-up, the association of depression symptoms with AMI risk was attenuated. Relative risk for AMI with anxiety symptoms and MSAD weakened when participants with chronic disorders were excluded. CONCLUSION: Self-reported symptoms of depression and anxiety, especially if recurrent, were moderately associated with the risk of incident AMI. We had some indications that these associations might partly reflect reverse causation or confounding from common chronic diseases.

Risk of acute myocardial infarction: dyslipidemia more detrimental for men than women.

BACKGROUND: Endogenous estrogens prevent lipid peroxidation, which is pivotal in atherogenesis. Dyslipidemia may therefore be more dangerous for men than for women as a risk factor for acute myocardial infarction (AMI). A differential effect by sex has not been empirically established. METHODS: In a prospective population-based cohort study of 23,525 women and 20,725 men younger than 60 years of age at baseline, we followed participants for 12 years for a first AMI. By calculating the proportion of AMI among men with dyslipidemia attributable to the synergism between male sex and dyslipidemia, we assessed the degree to which dyslipidemia is more detrimental for men than for women. RESULTS: Dyslipidemia and male sex enhanced the effect of one another in relation to AMI risk. The proportion of AMI cases among men with dyslipidemia attributable to this synergism alone was 0.46 (95% confidence interval = 0.35 to 0.57) for high total serum cholesterol, 0.23 (0.05 to 0.41) for low high-density lipoprotein (HDL) cholesterol, and 0.52 (0.42 to 0.62) for high non-HDL cholesterol. In contrast, obesity and hypertension were equally detrimental for men and women in relation to AMI risk, with a corresponding attributable proportion of 0.02 (-0.21 to 0.25) and -0.01 (-0.27 to 0.24), respectively. CONCLUSIONS: Current clinical guidelines of dyslipidemia management do not distinguish between men and women in relation to primary prevention of AMI. Our results suggest that in middle age, dyslipidemia is much more detrimental for men than for women, and that preventing dyslipidemia has a greater potential to reduce the occurrence of AMI among men.

Insomnia and high-sensitivity C-reactive protein: the HUNT study, Norway.

OBJECTIVE: To explore the hypothesis that insomnia may increase the risk of coronary heart disease through inflammatory mechanisms. METHODS: The association of high-sensitivity C-reactive protein (hsCRP) with self-reported symptoms of insomnia was examined. Participants were 8547 men and nonpregnant women who answered one or more insomnia-related questions and who had available hsCRP measurements in the Nord-Trøndelag Health Study. In multivariable linear regression analyses of the logarithm of hsCRP, we adjusted for established cardiovascular risk factors, psychosocial distress, chronic pain, and chronic somatic disorders. RESULTS: Among men, difficulties initiating sleep and nonrestorative sleep were associated with increasing hsCRP levels after adjusting for age (B = 0.07, 95% confidence interval [CI] = 0.01-0.14, p for trend = .02 and B = 0.09, 95% CI = 0.02-0.15, p for trend = .006), but after multivariable adjustment, the associations were attenuated (B = 0.03, 95% CI = -0.03 to 0.09, p for trend = .30 and B = 0.06, 95% CI = -0.00 to 0.12, p for trend = .05). HsCRP was not associated with other insomnia-related symptoms. In women, there was no evidence for any association of symptoms of insomnia with hsCRP levels. Results indicated sex differences in the association between sleep characteristics and CRP (difficulties maintaining sleep, p interaction = .018; cumulative number of symptoms of insomnia, p interaction = .014; and symptoms of insomnia influencing work performance, p interaction = .039). CONCLUSIONS: There were no consistent associations between symptoms of insomnia and hsCRP levels. Our results do not support the hypothesis that inflammation, as reflected by elevated levels of hsCRP, is an important factor linking insomnia to coronary heart disease.

Metabolic syndrome in Poland - the PONS Study.

INTRODUCTION: In Central and Eastern European countries, cardiovascular disorders (CVD) in middle age are much more common than in Western Europe, and it is imperative to understand the causes underlying this excess disease burden. The metabolic syndrome comprises a constellation of metabolic abnormalities that increase the risk of cardiovascular disease. METHODS: Data were obtained by structured interview, and by measurements of anthropometric factors and blood analyses among 3,862 individuals. Metabolic syndrome was defined according the International Diabetes Federation Task Force on Epidemiology and Prevention, as the presence of at least 3 of 5 abnormalities: 1) abdominal obesity, 2) glucose intolerance, 3) high triglycerides, 4) low HDL cholesterol, 5) high blood pressure. RESULTS: Overall, 1,518 participants (39.5%) had metabolic syndrome. The prevalence among females was 34.3% (877 females) vs. 49.9% (641 males) among males, and increased with age in both genders. Abdominal obesity was the most common abnormality (2,897 participants, 75.1%), followed by high blood pressure (2,741 participants, 71%), glucose intolerance (1,437 participants, 37.3%), elevated triglycerides (817 participants, 21.2%) and low HDL (615 participants, 15.9%). CONCLUSION: The prevalence of metabolic syndrome and metabolic abnormalities is high and represents strong risk factors for CVD morbidity and mortality. However, these factors are all potentially preventable by lifestyle modification and/or by pharmacological treatment. There is an urgent need for the health service to act, and to increase public awareness of metabolic syndrome.