Severe depression and all-cause and cause-specific mortality in Scotland: 20 year national cohort study.

BACKGROUND: Understanding cause of death in people with depression could inform approaches to reducing premature mortality. AIM: To describe all-cause and cause-specific mortality for people with severe depression in Scotland, by sex, relative to the general population. METHOD: We performed a retrospective cohort study, using psychiatric hospital admission data linked to death data, to identify adults (≥18 years old) with severe depression and ascertain cause-specific deaths, during 2000-2019. We estimated relative all-cause and cause-specific mortality for people with severe depression using standardised mortality ratios (SMRs), stratified by sex using the whole Scottish population as the standard. RESULTS: Of 28 808 people with severe depression, 7903 (27.4%) died during a median follow-up of 8.7 years. All-cause relative mortality was over three times higher than expected (SMR, both sexes combined: 3.26, 95% CI 3.19-3.34). Circulatory disease was the leading cause of death, and, among natural causes of death, excess relative mortality was highest for circulatory diseases (SMR 2.51, 2.40-2.66), respiratory diseases (SMR 3.79, 3.56-4.01) and 'other' causes (SMR 4.10, 3.89-4.30). Among circulatory disease subtypes, excess death was highest for cerebrovascular disease. Both males and females with severe depression had higher all-cause and cause-specific mortality than the general population. Suicide had the highest SMR among both males (SMR 12.44, 95% CI 11.33-13.54) and females (22.86, 95% CI 20.35-25.36). CONCLUSION: People with severe depression have markedly higher all-cause mortality than the general population in Scotland, with relative mortality varying by cause of death. Effective interventions are needed to reduce premature mortality for people with severe depression.

Non-pharmacological interventions for the treatment of post-stroke fatigue: A systematic review.

BACKGROUND: Post-stroke fatigue (PSF) affects 50% of stroke survivors. Current guidance on management of this condition is limited. AIMS: This systematic review and meta-analysis aimed to identify and analyze all randomized clinical trials (RCTs) of non-pharmacological interventions for the treatment of PSF. SUMMARY OF REVIEW: Six electronic databases were searched from inception to January 2023 for English-language RCTs investigating the efficacy of non-pharmacological interventions versus passive controls in patients with PSF. The primary outcome was fatigue severity at the end of the intervention. The Cochrane risk-of-bias (ROB)2 tool was used to assess evidence quality. A total of 7990 records were retrieved, 333 studies were scrutinized, and 13 completed RCTs (484 participants) were included. Interventions included psychological therapies, physical therapies, and brain stimulation. Nine studies provided sufficient data for meta-analysis, of which seven also had follow-up data. Fatigue severity was lower in the intervention groups at the end of the intervention compared with control (participants = 310, standardized mean difference (SMD) = -0.57, 95% confidence intervals (CIs) (-0.87 to -0.28)) and at follow-up (participants = 112, SMD = -0.36, 95% CIs (-0.83 to 0.10)). Certainty in the effect estimate was downgraded to low for a serious ROB and imprecision. Subgroup analysis revealed significant benefits with physical therapy and brain stimulation but not psychological therapies, though sample sizes were low. CONCLUSION: Non-pharmacological interventions improved fatigue but the quality of evidence was low. Further RCTs are needed for PSF management.

Association of socioeconomic status with 30-day survival following out-of-hospital cardiac arrest in Scotland, 2011-2020.

BACKGROUND AND AIMS: The aim of this study was to investigate the crude and adjusted association of socioeconomic status with 30-day survival after out-of-hospital cardiac arrest (OHCA) in Scotland and to assess whether the effect of this association differs by sex or age. METHODS: This is a population-based, retrospective cohort study, including non-traumatic, non-Emergency Medical Services witnessed patients with OHCA where resuscitation was attempted by the Scottish Ambulance Service, between April 1, 2011 and March 1, 2020. Socioeconomic status was defined using the Scottish Index of Multiple Deprivation (SIMD). The primary outcome was 30-day survival after OHCA. Crude and adjusted associations of SIMD quintile with 30-day survival after OHCA were estimated using logistic regression. Effect modification by age and sex was assessed by stratification. RESULTS: Crude analysis showed lower odds of 30-day survival in the most deprived quintile relative to least deprived (OR 0.74, 95%CI 0.63-0.88). Adjustment for age, sex and urban/rural residency decreased the relative odds of survival further (OR 0.56, 95%CI 0.47-0.67). The strongest association was observed in males < 45 years old. Across quintiles of increasing deprivation, evidence of decreasing trends in the proportion of those presenting with shockable initial cardiac rhythm, those receiving bystander cardiopulmonary resuscitation and 30-day survival after OHCA were found. CONCLUSIONS: Socioeconomic status is associated with 30-day survival after OHCA in Scotland, favouring people living in the least deprived areas. This was not explained by confounding due to age, sex or urban/rural residency. The strongest association was observed in males < 45 years old.

Association between sex and survival after out-of-hospital cardiac arrest: A systematic review and meta-analysis.

The current literature on sex differences in 30-day survival following out-of-hospital cardiac arrest (OHCA) is conflicting, with 3 recent systematic reviews reporting opposing results. To address these contradictions, this systematic literature review and meta-analysis aimed to synthesize the literature on sex differences in survival after OHCA by including only population-based studies and through separate meta-analyses of crude and adjusted effect estimates. MEDLINE and Embase databases were systematically searched from inception to March 23, 2022 to identify observational studies reporting sex-specific 30-day survival or survival until hospital discharge after OHCA. Two meta-analyses were conducted. The first included unadjusted effect estimates of the association between sex and survival (comparing males vs females), whereas the second included effect estimates adjusted for possible mediating and/or confounding variables. The PROSPERO registration number was CRD42021237887, and the search identified 6712 articles. After the screening, 164 potentially relevant articles were identified, of which 26 were included. The pooled estimate for crude effect estimates (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.22-1.66) indicated that males have a higher chance of survival after OHCA than females. However, the pooled estimate for adjusted effect estimates shows no difference in survival after OHCA between males and females (OR, 0.93; 95% CI, 0.84-1.03). Both meta-analyses involved high statistical heterogeneity between studies: crude pooled estimate I2 = 95.7%, adjusted pooled estimate I2 = 91.3%. There does not appear to be a difference in survival between males and females when effect estimates are adjusted for possible confounding and/or mediating variables in non-selected populations.

Development and Validation of a Lifetime Risk Model for Kidney Failure and Treatment Benefit in Type 2 Diabetes: 10-Year and Lifetime Risk Prediction Models.

BACKGROUND AND OBJECTIVES: Individuals with type 2 diabetes are at a higher risk of developing kidney failure. The objective of this study was to develop and validate a decision support tool for estimating 10-year and lifetime risks of kidney failure in individuals with type 2 diabetes as well as estimating individual treatment effects of preventive medication. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The prediction algorithm was developed in 707,077 individuals with prevalent and incident type 2 diabetes from the Swedish National Diabetes Register for 2002-2019. Two Cox proportional regression functions for kidney failure (first occurrence of kidney transplantation, long-term dialysis, or persistent eGFR <15 ml/min per 1.73 m2) and all-cause mortality as respective end points were developed using routinely available predictors. These functions were combined into life tables to calculate the predicted survival without kidney failure while using all-cause mortality as the competing outcome. The model was externally validated in 256,265 individuals with incident type 2 diabetes from the Scottish Care Information Diabetes database between 2004 and 2019. RESULTS: During a median follow-up of 6.8 years (interquartile range, 3.2-10.6), 8004 (1%) individuals with type 2 diabetes in the Swedish National Diabetes Register cohort developed kidney failure, and 202,078 (29%) died. The model performed well, with c statistics for kidney failure of 0.89 (95% confidence interval, 0.88 to 0.90) for internal validation and 0.74 (95% confidence interval, 0.73 to 0.76) for external validation. Calibration plots showed good agreement in observed versus predicted 10-year risk of kidney failure for both internal and external validation. CONCLUSIONS: This study derived and externally validated a prediction tool for estimating 10-year and lifetime risks of kidney failure as well as life years free of kidney failure gained with preventive treatment in individuals with type 2 diabetes using easily available clinical predictors. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2022_11_04_CJN05020422.mp3.

High-sensitivity cardiac troponin and the diagnosis of myocardial infarction in patients with kidney impairment.

The benefit and utility of high-sensitivity cardiac troponin (hs-cTn) in the diagnosis of myocardial infarction in patients with kidney impairment is unclear. Here, we describe implementation of hs-cTnI testing on the diagnosis, management, and outcomes of myocardial infarction in patients with and without kidney impairment. Consecutive patients with suspected acute coronary syndrome enrolled in a stepped-wedge, cluster-randomized controlled trial were included in this pre-specified secondary analysis. Kidney impairment was defined as an eGFR under 60mL/min/1.73m2. The index diagnosis and primary outcome of type 1 and type 4b myocardial infarction or cardiovascular death at one year were compared in patients with and without kidney impairment following implementation of hs-cTnI assay with 99th centile sex-specific diagnostic thresholds. Serum creatinine concentrations were available in 46,927 patients (mean age 61 years; 47% women), of whom 9,080 (19%) had kidney impairment. hs-cTnIs were over 99th centile in 46% and 16% of patients with and without kidney impairment. Implementation increased the diagnosis of type 1 infarction from 12.4% to 17.8%, and from 7.5% to 9.4% in patients with and without kidney impairment (both significant). Patients with kidney impairment and type 1 myocardial infarction were less likely to undergo coronary revascularization (26% versus 53%) or receive dual anti-platelets (40% versus 68%) than those without kidney impairment, and this did not change post-implementation. In patients with hs-cTnI above the 99th centile, the primary outcome occurred twice as often in those with kidney impairment compared to those without (24% versus 12%, hazard ratio 1.53, 95% confidence interval 1.31 to 1.78). Thus, hs-cTnI testing increased the identification of myocardial injury and infarction but failed to address disparities in management and outcomes between those with and without kidney impairment.

Incidence, characteristics and outcomes of out-of-hospital cardiac arrests in patients with psychiatric illness: A systematic review.

AIM: To conduct a systematic literature review of the existing evidence on incidence, characteristics and outcomes after out-of-hospital cardiac arrest (OHCA) in patients with psychiatric illness. METHODS: We searched Embase, Medline, PsycINFO and Web of Science using a comprehensive electronic search strategy to identify observational studies reporting on OHCA incidence, characteristics or outcomes by psychiatric illness status. One reviewer screened all titles and abstracts, and a second reviewer screened a random 10%. Two reviewers independently performed data extraction and quality assessment. RESULTS: Our search retrieved 11,380 studies, 10 of which met our inclusion criteria (8 retrospective cohort studies and two nested case-control studies). Three studies focused on depression, whilst seven included various psychiatric conditions. Among patients with an OHCA, those with psychiatric illness (compared to those without) were more likely to have: an arrest in a private location; an unwitnessed arrest; more comorbidities; less bystander cardiopulmonary resuscitation; and an initial non-shockable rhythm. Two studies reported on OHCA incidence proportion and two reported on survival, showing higher risk, but lower survival, in patients with psychiatric illness. CONCLUSION: Psychiatric illness in relation to OHCA incidence and outcomes has rarely been studied and only a handful of studies have reported on OHCA characteristics, highlighting the need for further research in this area. The scant existing literature suggests that psychiatric illness may be associated with higher risks of OHCA, unfavourable characteristics and poorer survival. Future studies should further investigate these links and the role of potential contributory factors such as socioeconomic status and comorbidities.

Long-term mortality and recurrent vascular events in lacunar versus non-lacunar ischaemic stroke: A cohort study.

Introduction: Studies of differences in very long-term outcomes between people with lacunar/small vessel disease (SVD) versus other types of ischaemic stroke report mixed findings, with limited data on myocardial infarction (MI). We investigated whether long-term mortality, recurrent stroke and MI risks differ in people with versus without lacunar/SVD ischaemic stroke. Patients and methods: We included first-ever strokes from a hospital-based stroke cohort study recruited in 2002-2005. We compared risks of death, recurrent stroke and MI during follow-up among lacunar/SVD versus other ischaemic stroke subtypes using Cox regression, adjusting for confounding factors. Results: We included 812 participants, 283 with lacunar/SVD ischaemic stroke and 529 with other stroke. During a median of 9.2 years (interquartile range 3.1-11.8), there were 519 deaths, 181 recurrent strokes and 79 MIs. Lacunar/SVD stroke was associated with lower mortality (adjusted HR 0.79, 95% CI 0.65 to 0.95), largely due to markedly lower all-cause mortality in the first year. From one year onwards this difference attenuated, with all-cause mortality only slightly and not statistically significantly lower in the lacunar/SVD group (0.86, 95% CI 0.70 to 1.05). There was no clear difference in risk of recurrent stroke (HR 0.84, 95% CI 0.61-1.15) or MI (HR 0.83, 95% CI 0.52-1.34). Conclusion: Long-term risks of all-cause mortality, recurrent stroke and MI are similar, or only slightly lower, in patients with lacunar/SVD as compared to other ischaemic stroke. Patients and physicians should be as vigilant in optimising short- and long-term secondary prevention of vascular events in lacunar/SVD as for other stroke types.

Association of measures of socioeconomic position with survival following out-of-hospital cardiac arrest: A systematic review.

BACKGROUND: Survival following out-of-hospital cardiac arrest (OHCA) is low, and poor survival appears associated with low socioeconomic position (SEP). We aimed to synthesise the evidence regarding association of specific SEP measures with OHCA survival, as well as effect modification and potential mediators, with the goal of informing efforts to improve survival by highlighting characteristics of populations requiring additional resources, and identifying modifiable factors. METHODS: MEDLINE and Embase databases were searched on 23 May 2019. Quantitative primary studies considering the association of any SEP measure with any OHCA survival measure were eligible. SEP could be measured at the level of the patient, their residential area, or OHCA location. Data on study characteristics and outcomes were extracted and a narrative review performed; this considered the evidence for overall SEP-survival association, variation in association of different SEP measures with survival, effect modification, and mediation. RESULTS: Twenty-three studies were included. These were highly heterogeneous, particularly regarding SEP measures and eligibility criteria. Several studies report a SEP-survival association, with this being almost exclusively in the direction of lower survival with lower SEP. There is some indication that the education-survival association is particularly consistent but further work is needed to increase confidence here. No evidence of effect modification by age, sex or other factors was seen, although few studies considered this. No mediators were conclusively identified. CONCLUSIONS: Low SEP is associated with poorer OHCA survival in at least some settings. It may be appropriate to consider populations' socioeconomic characteristics when targeting interventions to improve OHCA survival.

Long-term all-cause mortality and cardiovascular outcomes in Scottish children after initiation of renal replacement therapy: a national cohort study.

BACKGROUND: Data on long-term outcomes in children who have received renal replacement therapy (RRT) for end-stage renal disease are limited. METHODS: We studied long-term survival and incidence of fatal and nonfatal cardiovascular disease (CVD) events and determinants of these outcomes in children who initiated RRT between 1961 and 2013 using data from the Scottish Renal Registry (SRR). Linkage to morbidity records was available from 1981. RESULTS: A total of 477 children of whom 55% were boys, almost 50% had congenital urinary tract disease (CAKUT), 10% received a transplant as the first mode of RRT and almost 60% were over 11 years of age at start of RRT were followed for a median of 17.8 years (interquartile range (IQR) 8.7-26.6 years). Survival was 87.3% (95% confidence interval (CI) 84.0-90.1) at 10 years and 77.6% (95% CI 73.3-81.7) at 20 years. During a median follow-up of 14.96 years (IQR 7.1-22.9), 20.9% of the 381 patients with morbidity data available had an incident of CVD event. Age < 2 years at start of RRT, receiving dialysis rather than a kidney transplant and primary renal disease (PRD) other than CAKUT or glomerulonephritis (GN), were associated with a higher risk of all-cause mortality. Male sex, receiving dialysis rather than a kidney transplant and PRD other than CAKUT or GN, was associated with a higher risk of CVD incidence. CONCLUSIONS: Mortality and CVD incidence among children receiving RRT are high. PRD and RRT modality were associated with increased risk of both all-cause mortality and CVD incidence.

Acute kidney injury in the UK: a replication cohort study of the variation across three regional populations.

OBJECTIVES: A rapid growth in the reported rates of acute kidney injury (AKI) has led to calls for greater attention and greater resources for improving care. However, the reported incidence of AKI also varies more than tenfold between previous studies. Some of this variation is likely to stem from methodological heterogeneity. This study explores the extent of cross-population variation in AKI incidence after minimising heterogeneity. DESIGN: Population-based cohort study analysing data from electronic health records from three regions in the UK through shared analysis code and harmonised methodology. SETTING: Three populations from Scotland, Wales and England covering three time periods: Grampian 2003, 2007 and 2012; Swansea 2007; and Salford 2012. PARTICIPANTS: All residents in each region, aged 15 years or older. MAIN OUTCOME MEASURES: Population incidence of AKI and AKI phenotype (severity, recovery, recurrence). Determined using shared biochemistry-based AKI episode code and standardised by age and sex. RESULTS: Respectively, crude AKI rates (per 10 000/year) were 131, 138, 139, 151 and 124 (p=0.095), and after standardisation for age and sex: 147, 151, 146, 146 and 142 (p=0.257) for Grampian 2003, 2007 and 2012; Swansea 2007; and Salford 2012. The pattern of variation in crude rates was robust to any modifications of the AKI definition. Across all populations and time periods, AKI rates increased substantially with age from ~20 to ~550 per 10 000/year among those aged <40 and ≥70 years. CONCLUSION: When harmonised methods are used and age and sex differences are accounted for, a similar high burden of AKI is consistently observed across different populations and time periods (~150 per 10 000/year). There are particularly high rates of AKI among older people. Policy-makers should be careful not draw simplistic assumptions about variation in AKI rates based on comparisons that are not rigorous in methodological terms.

Performance of Cardiovascular Disease Risk Scores in People Diagnosed With Type 2 Diabetes: External Validation Using Data From the National Scottish Diabetes Register.

OBJECTIVE: To evaluate the performance of five cardiovascular disease (CVD) risk scores developed in diabetes populations and compare their performance to QRISK2. RESEARCH DESIGN AND METHODS: A cohort of people diagnosed with type 2 diabetes between 2004 and 2016 was identified from the Scottish national diabetes register. CVD events were identified using linked hospital and death records. Five-year risk of CVD was estimated using each of QRISK2, ADVANCE (Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation), Cardiovascular Health Study (CHS), New Zealand Diabetes Cohort Study (NZ DCS), Fremantle Diabetes Study, and Swedish National Diabetes Register (NDR) risk scores. Discrimination and calibration were assessed using the Harrell C statistic and calibration plots, respectively. RESULTS: The external validation cohort consisted of 181,399 people with type 2 diabetes and no history of CVD. There were 14,081 incident CVD events within 5 years of follow-up. The 5-year observed risk of CVD was 9.7% (95% CI 9.6, 9.9). C statistics varied between 0.66 and 0.67 for all risk scores. QRISK2 overestimated risk, classifying 87% to be at high risk for developing CVD within 5 years; ADVANCE underestimated risk, and the Swedish NDR risk score calibrated well to observed risk. CONCLUSIONS: None of the risk scores performed well among people with newly diagnosed type 2 diabetes. Using these risk scores to predict 5-year CVD risk in this population may not be appropriate.

High-Sensitivity Cardiac Troponin and the Risk Stratification of Patients With Renal Impairment Presenting With Suspected Acute Coronary Syndrome.

BACKGROUND: High-sensitivity cardiac troponin testing may improve the risk stratification and diagnosis of myocardial infarction, but concentrations can be challenging to interpret in patients with renal impairment, and the effectiveness of testing in this group is uncertain. METHODS: In a prospective multicenter study of consecutive patients with suspected acute coronary syndrome, we evaluated the performance of high-sensitivity cardiac troponin I in those with and without renal impairment (estimated glomerular filtration rate <60mL/min/1.73m2). The negative predictive value and sensitivity of troponin concentrations below the risk stratification threshold (5 ng/L) at presentation were reported for a primary outcome of index type 1 myocardial infarction, or type 1 myocardial infarction or cardiac death at 30 days. The positive predictive value and specificity at the 99th centile diagnostic threshold (16 ng/L in women, 34 ng/L in men) was determined for index type 1 myocardial infarction. Subsequent type 1 myocardial infarction and cardiac death were reported at 1 year. RESULTS: Of 4726 patients identified, 904 (19%) had renal impairment. Troponin concentrations <5 ng/L at presentation identified 17% of patients with renal impairment as low risk for the primary outcome (negative predictive value, 98.4%; 95% confidence interval [CI], 96.0%-99.7%; sensitivity 98.9%; 95%CI, 97.5%-99.9%), in comparison with 56% without renal impairment (P<0.001) with similar performance (negative predictive value, 99.7%; 95% CI, 99.4%-99.9%; sensitivity 98.4%; 95% CI, 97.2%-99.4%). The positive predictive value and specificity at the 99th centile were lower in patients with renal impairment at 50.0% (95% CI, 45.2%-54.8%) and 70.9% (95% CI, 67.5%-74.2%), respectively, in comparison with 62.4% (95% CI, 58.8%-65.9%) and 92.1% (95% CI, 91.2%-93.0%) in those without. At 1 year, patients with troponin concentrations >99th centile and renal impairment were at greater risk of subsequent myocardial infarction or cardiac death than those with normal renal function (24% versus 10%; adjusted hazard ratio, 2.19; 95% CI, 1.54-3.11). CONCLUSIONS: In suspected acute coronary syndrome, high-sensitivity cardiac troponin identified fewer patients with renal impairment as low risk and more as high risk, but with lower specificity for type 1 myocardial infarction. Irrespective of diagnosis, patients with renal impairment and elevated cardiac troponin concentrations had a 2-fold greater risk of a major cardiac event than those with normal renal function, and should be considered for further investigation and treatment. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01852123.

Obesity and risk of death or dialysis in younger and older patients on specialized pre-dialysis care.

BACKGROUND: Obesity is associated with increased mortality and accelerated decline in kidney function in the general population. Little is known about the effect of obesity in younger and older pre-dialysis patients. The aim of this study was to assess the extent to which obesity is a risk factor for death or progression to dialysis in younger and older patients on specialized pre-dialysis care. METHOD: In a multicenter Dutch cohort study, 492 incident pre-dialysis patients (>18y) were included between 2004-2011 and followed until start of dialysis, death or October 2016. We grouped patients into four categories of baseline body mass index (BMI): <20, 20-24 (reference), 25-29, and ≥30 (obesity) kg/m2 and stratified patients into two age categories (<65y or ≥65y). RESULTS: The study population comprised 212 patients younger than 65 years and 280 patients 65 years and older; crude cumulative risk of dialysis and mortality at the end of follow-up were 66% and 4% for patients <65y and 64% and 14%, respectively, for patients ≥65y. Among the <65y patients, the age-sex standardized combined outcome rate was 2.3 times higher in obese than those with normal BMI, corresponding to an excess rate of 35 events/100 patient-years. After multivariable adjustment the hazard ratios (HR) (95% CI) for the combined endpoint by category of increasing BMI were, for patients <65y, 0.92 (0.41-2.09), 1 (reference), 1.76 (1.16-2.68), and 1.81 (1.17-2.81). For patients ≥65y the BMI-specific HRs were 1.73 (0.97-3.08), 1 (reference), 1.25 (0.91-1.71) and 1.30 (0.79-1.90). In the competing risk analysis, taking dialysis as the event of interest and death as a competing event, the BMI-specific multivariable adjusted subdistribution HRs (95% CI) were, for patients <65y, 0.90 (0.38-2.12), 1 (reference), 1.47 (0.96-2.24) and 1.72 (1.15-2.59). For patients ≥65y the BMI-specific SHRs (95% CI) were 1.68 (0.93-3.02), 1 (reference), 1.50 (1.05-2.14) and 1.80 (1.23-2.65). CONCLUSION: We found that obesity in younger pre-dialysis patients and being underweight in older pre-dialysis patients are risk factors for starting dialysis and for death, compared with those with a normal BMI.

Health-related quality of life trajectories during predialysis care and associated illness perceptions.

OBJECTIVE: To identify health-related quality of life (HRQOL) trajectories during 18 months of predialysis care and associated patient characteristics and illness perceptions. METHOD: 396 incident predialysis patients participating in the prospective PREdialysis PAtient REcord-2 study completed every 6 months the 36-item Short Form Health Survey (i.e., mental and physical HRQOL) and Revised Illness Perception Questionnaire. HRQOL trajectories were examined using latent class growth models, and associated baseline factors were identified using logistic regression. Analyses for illness perceptions were adjusted for demographic and clinical characteristics. RESULTS: Three physical HRQOL trajectories (low-stable [34.1% of the sample], medium-declining [32.5%], and high-increasing [33.4%]) and two mental HRQOL trajectories (low-stable [38.7%] and high-stable [61.3%]) were identified. Increased odds for a low-stable physical HRQOL trajectory were detected in older patients (Odds ratio [OR] = 1.04), patients with cardiovascular disease (OR = 2.1) and patients who believed to a lesser extent they can personally control their disease (ORadj = 0.88). Increased odds for both a low-stable physical and mental HRQOL trajectory were detected in patients who believed to a higher extent that their disease is cyclical, has negative consequences, causes negative feelings, and in patients who believed to a lesser extent they understand their disease (ORadj ranged between 0.84 and 1.36). Additionally, patients who attributed more symptoms to their disease had increased odds for a medium-declining (ORadj = 1.21) and low-stable physical HRQOL trajectory (ORadj = 1.50). CONCLUSIONS: Older age and cardiovascular disease are markers for unfavorable physical HRQOL trajectories, and stronger negative illness perceptions are markers for unfavorable physical and mental HRQOL trajectories. Targeting negative illness perceptions could possibly optimize HRQOL during predialysis care. (PsycINFO Database Record

Measuring the Association Between Body Mass Index and All-Cause Mortality in the Presence of Missing Data: Analyses From the Scottish National Diabetes Register.

Incorrectly handling missing data can lead to imprecise and biased estimates. We describe the effect of applying different approaches to handling missing data in an analysis of the association between body mass index and all-cause mortality among people with type 2 diabetes. We used data from the Scottish diabetes register that were linked to hospital admissions data and death registrations. The analysis was based on people diagnosed with type 2 diabetes between 2004 and 2011, with follow-up until May 31, 2014. The association between body mass index and mortality was investigated using Cox proportional hazards models. Findings were compared using 4 different missing-data methods: complete-case analysis, 2 multiple-imputation models, and nearest-neighbor imputation. There were 124,451 cases of type 2 diabetes, among which there were 17,085 deaths during 787,275 person-years of follow-up. Patients with missing data (24.8%) had higher mortality than those without missing data (adjusted hazard ratio = 1.36, 95% confidence interval: 1.31, 1.41). A U-shaped relationship between body mass index and mortality was observed, with the lowest hazard ratios occurring among moderately obese people, regardless of the chosen approach for handling missing data. Missing data may affect absolute and relative risk estimates differently and should be considered in analyses of routinely collected data.

Socioeconomic status, comorbidity and mortality in patients with type 2 diabetes mellitus in Scotland 2004-2011: a cohort study.

BACKGROUND: Mortality in people with and without diabetes often exhibits marked social patterning, risk of death being greater in deprived groups. This may reflect deprivation-related differences in comorbid disease (conditions additional to diabetes itself). This study sought to determine whether the social patterning of mortality in a population with type 2 diabetes mellitus (T2DM) is explained by differential comorbidity. METHODS: Hospital records for 70 197 men and 56 451 women diagnosed with T2DM at 25 years of age and above in Scotland during the period 2004-2011 were used to construct comorbidity histories. Sex-specific logistic models were fitted to predict mortality at 1 year after diagnosis with T2DM, predicted initially by age and socioeconomic status (SES) then extended to incorporate in turn 5 representations of comorbidity (including the Charlson Index). The capacity of comorbidity to explain social mortality gradients was assessed by observing the change in regression coefficients for SES following the addition of comorbidity. RESULTS: After adjustment for age and Charlson Index, the OR for the contrast between the least deprived and most deprived quintiles of SES for men was 0.79 (95% CI 0.67 to 0.94). For women, the OR was 0.81 (0.67 to 0.97). Similar results were obtained for the 4 other comorbidity measures used. CONCLUSIONS: The social patterning of mortality in people with T2DM is not fully explained by differing levels of comorbid disease additional to T2DM itself. Other dimensions of deprivation are implicated in the elevated death rates observed in deprived groups of people with T2DM.

Illness Perceptions in Patients on Predialysis Care: Associations With Time Until Start of Dialysis and Decline of Kidney Function.

OBJECTIVES: Illness perceptions in patients with end-stage renal disease are associated with nonadherence and increased mortality. However, no data are available regarding the relationship between illness perceptions and accelerated disease progression in predialysis patients. METHODS: A total of 416 incident predialysis patients participating in a prospective cohort (PREPARE-2, Predialysis Patient Record-2) completed the Revised Illness Perception Questionnaire at the start of specialized predialysis care. The association between illness perceptions and time until start of dialysis was investigated using Cox regression models. Linear mixed modeling was used to test associations between illness perceptions and change of kidney function during predialysis care. Adjustments were made for sociodemographic, clinical, and biochemical factors. RESULTS: Five illness perceptions were associated with disease progression. Dialysis started earlier and kidney function declined faster (ml/min per 1.73 m/y) in patients who perceived their kidney disease as being cyclical in nature (adjusted hazard ratio [HRadj] = 1.32 [95% confidence interval {CI} = 1.11-1.56]; adjusted additional change = -0.64 [95% CI = -1.16 to -0.13]), having many negative consequences (HRadj = 1.47 [95% CI = 1.18-1.85]; adjusted additional change = -0.67 [-1.30 to -0.04]) and causing negative feelings (HRadj = 1.21 [95% CI = 1.03-1.42]; adjusted additional change = -0.65 [95% CI = -1.13 to -0.16]). In addition, kidney function declined faster in patients who perceived that their kidney disease cannot be personally controlled (adjusted additional change = -0.69 [95% CI = -1.31 to -0.09]) and who perceived that they did not fully understand their kidney disease (adjusted additional change = -0.53 [-1.05 to -0.01]). CONCLUSIONS: Stronger negative perceptions of illness at the start of predialysis care are a marker for accelerated disease progression. Detecting illness perceptions in predialysis patients may provide opportunities to intervene and slow down disease progression.

The Association of Effluent Ca125 with Peritoneal Dialysis Technique Failure.

UNLABELLED: ♦ BACKGROUND AND OBJECTIVES: Cancer antigen 125 (CA125) reflects the mesothelial cell mass lining the peritoneal membrane in individual patients. A decline or absence of mesothelial cells can be observed with duration of peritoneal dialysis (PD) therapy. Technique failure due to peritoneal membrane malfunction becomes of greater importance after 2 years of PD therapy in comparison to the initial period. In this study, we aimed to investigate the association between effluent CA125 and technique survival in incident PD patients with a PD therapy period of at least 2 years. ♦ METHODS: Within the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), a Dutch multicenter cohort including 2,000 incident dialysis patients, we identified all PD patients who developed technique failure after 2 years of PD therapy and randomly selected a number of them as cases in a nested case-control study. Controls were PD patients matched on follow-up time without technique failure. Cases and controls were included if they had a dialysate specimen available within 24 ± 6 months of PD therapy for retrospective CA125 determinations. Odds ratios for technique failure related to CA125 were estimated. We used a prospective cohort with incident PD patients from the Academic Medical Center-University of Amsterdam (AMC) for replication of effect estimates. In these patients, absolute risk of technique failure was estimated and related to effluent CA125 levels. ♦ RESULTS: A total of 38 PD patients were selected from the NECOSAD cohort. From the AMC cohort as replication cohort, 91 PD patients were included. Incidence rates of PD technique failure per 100 patient-years were 16.3 in the NECOSAD cohort and 12.9 in the AMC cohort. In both study populations CA125 levels below 12 - 14 kU/L were associated with an increased risk for technique failure. Technique survival rates in the AMC were 87% in patients with levels of CA125 above 12.1 kU/L and 65% for those with CA125 levels below this threshold after a maximum 5-year follow-up. ♦ CONCLUSIONS: Patients with high CA125 levels after at least 2 years of PD therapy tend to have better technique survival than patients with low CA125 levels. These results support the importance of effluent CA125 as a risk factor for dropout in long-term PD therapy.

Lipid levels and renal function decline in pre-dialysis patients.

BACKGROUND: Little is known about the effect of low-density lipoprotein (LDL) cholesterol, triglyceride (TG), and high-density lipoprotein (HDL) cholesterol levels on renal function decline in patients receiving specialized pre-dialysis care. METHODS: In the prospective PREPARE-2 study, incident patients starting pre-dialysis care were included when referred to one of the 25 participating Dutch specialized pre-dialysis outpatient clinics (2004-2011). Clinical and laboratory data were collected every 6 months. A linear mixed model was used to compare renal function decline between patients with LDL cholesterol, TG, or HDL cholesterol levels above and below the target goals (LDL cholesterol: <2.50 mmol/l, TG: <2.25 mmol/l, and HDL cholesterol: ≥1.00 mmol/l). Additionally the HDL/LDL cholesterol ratio was investigated (≥0.4). RESULTS: In our study population (n = 306), the median age was 69 years and 70% were male. Patients with LDL cholesterol levels above the target of 2.50 mmol/l experienced an accelerated renal function decline compared to patients with levels below the target (crude additional decline: 0.10 ml/min/1.73 m(2)/month, 95% CI 0.00-0.20; p < 0.05). A similar trend was found for TG levels above the target of 2.25 mmol/l (0.05 ml/min/1.73 m(2)/month, 95% CI -0.06 to 0.16) and for a HDL/LDL cholesterol ratio below 0.4 (0.06 ml/min/1.73 m(2)/month, 95% CI -0.05 to 0.18). Adjustment for potential confounders resulted in similar results, and the exclusion of patients who were prescribed lipid-lowering medication (statin, fibrate, or cholesterol absorption inhibitor) resulted in a slightly larger estimated effect. CONCLUSION: High levels of LDL cholesterol were associated with an accelerated renal function decline, independent of the prescription of lipid-lowering medication.