Stian Lydersen

Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis.

BACKGROUND Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality. METHODS In this collaborative meta-analysis of general population cohorts, we pooled standardised data for all-cause and cardiovascular mortality from studies containing at least 1000 participants and baseline information about eGFR and urine albumin concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality associated with eGFR and albuminuria, adjusted for potential confounders. FINDINGS The analysis included 105,872 participants (730,577 person-years) from 14 studies with urine albumin-to-creatinine ratio (ACR) measurements and 1,128,310 participants (4,732,110 person-years) from seven studies with urine protein dipstick measurements. In studies with ACR measurements, risk of mortality was unrelated to eGFR between 75 mL/min/1.73 m(2) and 105 mL/min/1.73 m(2) and increased at lower eGFRs. Compared with eGFR 95 mL/min/1.73 m(2), adjusted HRs for all-cause mortality were 1.18 (95% CI 1.05-1.32) for eGFR 60 mL/min/1.73 m(2), 1.57 (1.39-1.78) for 45 mL/min/1.73 m(2), and 3.14 (2.39-4.13) for 15 mL/min/1.73 m(2). ACR was associated with risk of mortality linearly on the log-log scale without threshold effects. Compared with ACR 0.6 mg/mmol, adjusted HRs for all-cause mortality were 1.20 (1.15-1.26) for ACR 1.1 mg/mmol, 1.63 (1.50-1.77) for 3.4 mg/mmol, and 2.22 (1.97-2.51) for 33.9 mg/mmol. eGFR and ACR were multiplicatively associated with risk of mortality without evidence of interaction. Similar findings were recorded for cardiovascular mortality and in studies with dipstick measurements. INTERPRETATION eGFR less than 60 mL/min/1.73 m(2) and ACR 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality risk in the general population. This study provides quantitative data for use of both kidney measures for risk assessment and definition and staging of chronic kidney disease. FUNDING Kidney Disease: Improving Global Outcomes (KDIGO), US National Kidney Foundation, and Dutch Kidney Foundation.Background A comprehensive evaluation of the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality is required for assessment of the impact of kidney function on risk in the general population, with implications for improving the definition and staging of chronic kidney disease (CKD).

International Comparison of the Relationship of Chronic Kidney Disease Prevalence and ESRD Risk

ESRD incidence is much lower in Europe compared with the United States. This study investigated whether this reflects a difference in the prevalence of earlier stages of chronic kidney disease (CKD) or other mechanisms. CKD prevalence in Norway was estimated from the population-based Health Survey of Nord-Trondelag County (HUNT II), which included 65,181 adults in 1995 through 1997 (participation rate 70.4%). Data were analyzed using the same methods as two US National Health and Nutrition Examination Surveys in 1988 through 1994 (n = 15,488) and 1999 through 2000 (n = 4101). The primary analysis used gender-specific cutoffs in estimating persistent albuminuria for CKD stages 1 and 2. ESRD rates and other relevant data were extracted from national registries. Total CKD prevalence in Norway was 10.2% (SE 0.5): CKD stage 1 (GFR >90 ml/min per 1.73 m2 and albuminuria), 2.7% (SE 0.3); stage 2 (GFR 60 to 89 ml/min per 1.73 m2 and albuminuria), 3.2% (SE 0.4); stage 3 (GFR 30 to 59 ml/min per 1.73 m2), 4.2% (SE 0.1); and stage 4 (GFR 15 to 29 ml/min per 1.73 m2), 0.2% (SE 0.01). This closely approximates reported US CKD prevalence (11.0% in 1988 through 1994 and 11.7% in 1999 through 2000). The relative risk for progression from CKD stages 3 or 4 to ESRD in US white patients compared with Norwegian patients was 2.5. This was only modestly modified by adjustment for age, gender, and diabetes. Age and GFR at start of dialysis were similar, hypertension and cardiovascular mortality in the populations were comparable, but US white patients were referred later to a nephrologist and had higher prevalence of obesity and diabetes. In conclusion, CKD prevalence in Norway was similar to that in the United States, suggesting that lower progression to ESRD rather than a smaller pool of individuals at risk accounts for the lower incidence of ESRD in Norway.

Comprehensive geriatric care for patients with hip fractures: a prospective, randomised, controlled trial

BACKGROUND Most patients with hip fractures are characterised by older age (>70 years), frailty, and functional deterioration, and their long-term outcomes are poor with increased costs. We compared the effectiveness and cost-effectiveness of giving these patients comprehensive geriatric care in a dedicated geriatric ward versus the usual orthopaedic care. METHODS We did a prospective, single-centre, randomised, parallel-group, controlled trial. Between April 18, 2008, and Dec 30, 2010, we randomly assigned home-dwelling patients with hip-fractures aged 70 years or older who were able to walk 10 m before their fracture, to either comprehensive geriatric care or orthopaedic care in the emergency department, to achieve the required sample of 400 patients. Randomisation was achieved via a web-based, computer-generated, block method with unknown block sizes. The primary outcome, analysed by intention to treat, was mobility measured with the Short Physical Performance Battery (SPPB) 4 months after surgery for the fracture. The type of treatment was not concealed from the patients or staff delivering the care, and assessors were only partly masked to the treatment during follow-up. This trial is registered with ClinicalTrials.gov, number NCT00667914. FINDINGS We assessed 1077 patients for eligibility, and excluded 680, mainly for not meeting the inclusion criteria such as living in a nursing home or being aged less than 70 years. Of the remaining patients, we randomly assigned 198 to comprehensive geriatric care and 199 to orthopaedic care. At 4 months, 174 patients remained in the comprehensive geriatric care group and 170 in the orthopaedic care group; the main reason for dropout was death. Mean SPPB scores at 4 months were 5·12 (SE 0·20) for comprehensive geriatric care and 4·38 (SE 0·20) for orthopaedic care (between-group difference 0·74, 95% CI 0·18-1·30, p=0·010). INTERPRETATION Immediate admission of patients aged 70 years or more with a hip fracture to comprehensive geriatric care in a dedicated ward improved mobility at 4 months, compared with the usual orthopaedic care. The results suggest that the treatment of older patients with hip fractures should be organised as orthogeriatric care. FUNDING Norwegian Research Council, Central Norway Regional Health Authority, St Olav Hospital Trust and Fund for Research and Innovation, Liaison Committee between Central Norway Regional Health Authority and the Norwegian University of Science and Technology, the Department of Neuroscience at the Norwegian University of Science and Technology, Foundation for Scientific and Industrial Research at the Norwegian Institute of Technology (SINTEF), and the Municipality of Trondheim.

Recommended tests for association in 2×2 tables

The asymptotic Pearsons chi-squared test and Fishers exact test have long been the most used for testing association in 2x2 tables. Unconditional tests preserve the significance level and generally are more powerful than Fishers exact test for moderate to small samples, but previously were disadvantaged by being computationally demanding. This disadvantage is now moot, as software to facilitate unconditional tests has been available for years. Moreover, Fishers exact test with mid-p adjustment gives about the same results as an unconditional test. Consequently, several better tests are available, and the choice of a test should depend only on its merits for the application involved. Unconditional tests and the mid-p approach ought to be used more than they now are. The traditional Fishers exact test should practically never be used.

Medical Complications in a Comprehensive Stroke Unit and an Early Supported Discharge Service

Background and Purpose— The aims of the study were to examine the frequency and timing of predefined medical complications in unselected acute stroke patients treated in an acute comprehensive stroke unit and an early supported discharge service. Methods— Four hundred eighty-nine acute stroke patients were included and followed up with assessments of 16 prespecified complications during the first week. Two hundred forty-four of the patients were randomly allocated to a 3-month follow-up. Results— During the first week, 312 of 489 patients (63.8%) experienced 1 or more complications. The most common complications were pain in 117 patients (23.9%), temperature ≥38°C in 116 (23.7%), progressing stroke in 90 (18.4%), urinary tract infection in 78 (16.0%), troponin T elevation without criteria of myocardial infarction in 57 (11.7%), chest infections in 55 (11.2%), nonserious falls in 36 (7.4%), and myocardial infarction in 22 (4.5%), whereas stroke recurrence, seizure, deep venous thrombosis, pulmonary embolism, shoulder pain, serious falls, other infections, and pressure sores were each present in ≤2.5% of patients. During the 3-month follow-up, 201 of 244 patients (82.4%) experienced at least 1 complication, the most common of which was pain, which occurred in 134 patients (53.3%), followed by urinary tract infection in 68 (27.9%) and nonserious falls in 61 (25.0%). The severity of stroke on admission was the most important risk factor for developing complications. Conclusions— This is the first study of complications in unselected acute stroke patients treated in a comprehensive stroke unit and early supported discharge service and shows that pain, progressing stroke, infections, myocardial infarction, and falls are common complications, whereas others occur infrequently. Most complications occur during the first 4 days, and stroke severity is the most important risk factor.

APOE ε4 lowers age at onset and is a high risk factor for Alzheimer's disease; A case control study from central Norway

BackgroundThe objective of this study was to analyze factors influencing the risk and timing of Alzheimers disease (AD) in central Norway. The APOE ε4 allele is the only consistently identified risk factor for late onset Alzheimers disease (LOAD). We have described the allele frequencies of the apolipoprotein E gene (APOE) in a large population of patients with AD compared to the frequencies in a cognitively-normal control group, and estimated the effect of the APOE ε4 allele on the risk and the age at onset of AD in this population.Methods376 patients diagnosed with AD and 561 cognitively-normal control individuals with no known first degree relatives with dementia were genotyped for the APOE alleles. Allele frequencies and genotypes in patients and control individuals were compared. Odds Ratio for developing AD in different genotypes was calculated.ResultsOdds Ratio (OR) for developing AD was significantly increased in carriers of the APOE ε4 allele compared to individuals with the APOE ε3/ε3 genotype. Individuals carrying APOE ε4/ε4 had OR of 12.9 for developing AD, while carriers of APOE ε2/ε4 and APOE ε3/ε4 had OR of 3.2 and 4.2 respectively. The effect of the APOE ε4 allele was weaker with increasing age. Carrying the APOE ε2 allele showed no significant protective effect against AD and did not influence age at onset of the disease. Onset in LOAD patients was significantly reduced in a dose dependent manner from 78.4 years in patients without the APOE ε4 allele, to 75.3 in carriers of one APOE ε4 allele and 72.9 in carriers of two APOE ε4 alleles. Age at onset in early onset AD (EOAD) was not influenced by APOE ε4 alleles.ConclusionAPOE ε4 is a very strong risk factor for AD in the population of central Norway, and lowers age at onset of LOAD significantly.

Prevalence, comorbidity and impact of irritable bowel syndrome in Norway

Objective. To study the prevalence of irritable bowel syndrome (IBS) and its comorbidity in a Norwegian adult population. Material and methods. In 2001, 11,078 inhabitants (aged 30–75 years) in Oppland County were invited to take part in a public health survey. A total of 4622 subjects (42%) completed the questionnaires on symptoms of IBS (Rome II criteria), comorbidity, health-care visits and medications. The impact of comorbidity on global health, working disability and use of health-care resources in subjects with IBS was explored by stepwise logistic regression. Results. The population prevalence of IBS was 388/4622 (8.4% (95% CI: 7.6–9.4%)) with a female predominance and an age-dependent decrease. The proportion who had consulted for IBS ranged from 51% among 30-year-olds to 79% in 75-year-olds (p=0.05). IBS was associated with musculoskeletal complaints (OR = 2.4–3.4 for six different items), fibromyalgia (OR = 3.6 [2.7–4.8]), mood disorder (OR = 3.3 (2.6–4.3)), reduced global health (OR = 2.6 (2.1–3.2)), working disability (OR = 1.6 (1.2–2.1)), more frequent health-care visits and use of medications (OR 1.7–2.3). When controlling for comorbidity, reduced global health (OR = 1.5 (1.1–2.0)) and use of alternative health care (OR = 1.7 (1.3–2.4)) remained associated with IBS. Severity of abdominal pain/discomfort was a predictor of having to seek a physician for IBS (OR = 1.3 (1.2–1.5)). Conclusions. Symptoms of IBS were reported by 8% of Norwegian adults and had resulted in consultations with physicians for the majority in the long run. Subjects with IBS in the community were characterized by frequent somatic and psychiatric comorbidity. Their observed reduced health, working disability and increased use of health resources were largely explained by comorbid symptoms and disorders.

Prehypertension, Obesity, and Risk of Kidney Disease: 20-Year Follow-up of the HUNT I Study in Norway

BACKGROUND The combined effect of blood pressure (BP) and body weight on risk of kidney disease has not been previously studied. To improve risk stratification in prehypertensive individuals (ie, BP, 120 to 139/80 to 89 mm Hg), we examined the interaction between BP and body weight on the risk of end-stage renal disease or chronic kidney disease (CKD)-related death. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS 74,986 adults participating in the first Health Study in Nord-Trøndelag (88% participation rate) were linked to the Norwegian Renal Registry and Cause of Death Registry. PREDICTORS BP and body weight were measured by using standard procedures, and other relevant covariates were obtained from an extensive questionnaire. OUTCOME & MEASUREMENTS Hazard ratios for treated end-stage renal disease and CKD-related death were calculated. RESULTS Mean systolic BP and body mass index (BMI) were 136.8 +/- 23.3 (SD) mm Hg and 25.2 +/- 3.9 kg/m(2), whereas 12.9% had treated hypertension at baseline, respectively. During a median follow-up of 21 years (1,345,882 person-years), 507 men (1.4%) and 319 women (0.8%) initiated renal replacement therapy (n = 157) or died of CKD (n = 669). Multiadjusted risk of these kidney outcomes increased continuously with no lower threshold for BP. The risk associated with body weight started to increase from a BMI of 25.0 kg/m(2). In participants with BP less than 120/80 mm Hg, risk did not increase with increasing BMI. In prehypertensive participants, multivariate adjusted hazard ratios in the BMI categories 18.5 to 24.9, 25.0 to 29.9, 30.0 to 34.9, and 35.0 kg/m(2) or greater were 1.21 (95% confidence interval [CI], 0.67 to 2.17), 1.10 (95% CI, 59 to 2.00), 2.66 (95% CI, 1.28 to 5.53), and 5.94 (95% CI, 1.94 to 18.20) compared with BP less than 120/80 mm Hg and BMI of 18.5 to 24.9 kg/m(2), respectively (P = 0.02 for trend). Corresponding risks in hypertensive participants were 2.13 (95% CI, 1.23 to 3.70), 2.40 (95% CI, 1.40 to 4.15), 3.32 (95% CI, 1.89 to 5.81), and 5.53 (95% CI, 3.01 to 10.20), respectively (P < 0.001 for trend). LIMITATIONS Baseline creatinine measurements were not available; hence, a secondary analysis was performed that excluded all individuals who experienced outcomes in the 5 years after the study start. CONCLUSIONS Participants with prehypertension are not at increased risk of serious kidney outcomes if BMI is less than 30.0 kg/m(2). However, the risk of kidney disease increases substantially if prehypertension is present in obese participants.

Stroke Unit Care Combined With Early Supported Discharge. Long-Term Follow-Up of a Randomized Controlled Trial

Background and Purpose— Early supported discharge from a stroke unit reduces the length of hospital stay. Evidence of a benefit for the patients is still unknown. The aim of this trial was to evaluate the long-term effects of an extended stroke unit service (ESUS), characterized by early supported discharge. The short-term effects were published previously. Methods— We performed a randomized controlled trial in which 320 acute stroke patients were allocated to either ordinary stroke unit service (OSUS) (160 patients) or stroke unit care with early supported discharge (160 patients). The ESUS consists of a mobile team that coordinates early supported discharge and further rehabilitation. Primary outcome was the proportion of patients who were independent as assessed by modified Rankin Scale (RS) (RS ≤2=global independence). Secondary outcomes measured at 52 weeks were performance on the Barthel Index (BI) (BI ≥95=independent in activities of daily living), differences in final residence, and analyses to identify patients who benefited most from an early supported discharge service. All assessments were blinded. Results— We found that 56.3% of the patients in the ESUS versus 45.0% in the OSUS were independent (RS ≤2) (P =0.045). The number needed to treat to achieve 1 independent patient in ESUS versus OSUS was 9. The odds ratio for independence was 1.56 (95% CI, 1.01 to 2.44). There were no significant differences in BI score and final residence. Patients with moderate to severe stroke benefited most from the ESUS. Conclusions— Stroke service based on treatment in a stroke unit combined with early supported discharge appears to improve the long-term clinical outcome compared with ordinary stroke unit care. Patients with moderate to severe stroke benefit most.

Self-rated health during adolescence: stability and predictors of change (Young-HUNT study, Norway)

Background: Self-rated health (SRH) is an important single-item variable used in many health surveys. It is a predictor for later mortality, morbidity and health service attendance. Therefore, it is important to study how SRH is influenced during adolescence. The present study examined the stability of SRH over a 4-year period in adolescence, and the factors predicting change in it. Methods: Analyses were based on 4-year longitudinal data from the Young-HUNT studies in Norway among adolescents aged 13–19 years. A total of 2800 students (81%) participated in the follow-up study, and 2399 of these were eligible for data analysis. Cross-tables for SRH at the start of the study (between 1995 and 1997) and 4 years later were used to estimate the stability over the period. Proportional odds logistic regression analyses of SRH during 2000–01 were carried out, controlling for initial SRH, independent variables at the start of the study and changes in the same independent variables over 4 years as covariates. Results: In 59% of the respondents, SRH remained unchanged through the 4-year observation period during adolescence. Fewer than 4% changed their ratings of SRH by two steps or more on a four-level scale. The self-assessed general well-being, health behaviour variables, being disabled in any way, and body dissatisfaction at the start of the study and the change of these predictors influenced SRH significantly during the 4-year observation. Being diagnosed with a medical condition, or specific mental or somatic health symptoms was of less importance for later SRH. Adolescents with more health service contacts at the start of the study, or who increase their attendance rate during the 4 years, report deterioration of SRH. Conclusion: SRH is a relatively stable construct during adolescence, and deteriorates consistently with a lack of general well-being, disability, healthcare attendance and health-compromising behaviour.