Five-year Risk Research Articles

Morbidity, Mortality and Normality after Autologous Stem-Cell Transplantation for Lymphoma: A Comprehensive, Single-Centre, Population-Based, Real-World Analysis of Patients Transplanted 1994-2016

Background: Autologous stem-cell transplantation (ASCT) is established lymphoma therapy, but the procedure has a substantial treatment-related mortality. Methods All 433 lymphoma patients who underwent ASCT at Karolinska Huddinge 1994-2016 were investigated, including long- and short-term mortality, causes of death, longitudinal laboratory values and anti-lymphoma treatments, harvested and transplanted CD34 cell amounts, infectious and other complications, microbiology findings, intensive care, drugs administered, chemotherapy-induced nausea, hospital stay, and secondary myeloid neoplasia. Findings: BEAM was the conditioning for 93%. The 100-day overall and non-lymphoma mortality were 7·2% and 5·6%. Stem cell harvests <5 million CD34 cells/kg correlated with inferior long- and short-term survival. At start of conditioning, elevated (both 3-9 and ≥10 mg/L) C-reactive protein (CRP) and creatinine but low albumin predicted inferior 100-day non-lymphoma mortality. Higher age (65-72 years) had no bearing on 100-day mortality. Delays between the last dose of chemotherapy and ASCT did not correlate with inferior outcome. Intravenous antibiotics was given to 97% (22% positive blood cultures) and parenteral nutrition to 86%. Fungal infections were rare. Aprepitant ameliorated nausea and vomiting. The median days for leukocyte engraftment and hospital discharge were 11 and 16. At one year, 86% and 76% had normalised haemoglobin and platelets. The cumulative five-year risk for secondary myeloid neoplasia was 4·1%, associated with smaller stem cell harvests. Interpretation: In ASCT for lymphoma, the harvest should be ≥5 million CD34 cells/kg. Before starting conditioning, patients should preferably show normal CRP, albumin, and creatinine. It is safe to postpone the procedure, and to transplant older patients. Funding: Funded by Stockholm County Council (clinical research appointment), Cancerfonden, and Svenska Sallskapet for Medicinsk Forskning (SSMF). Role of the funding source: the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Declaration of interests: The authors have no conflict of interest. Ethics Approval Statement: This study was approved by the Ethics Committee, Stockholm.

Variation in treatment and survival of older patients with non-metastatic breast cancer in five European countries: a population-based cohort study from the EURECCA Breast Cancer Group

BackgroundOlder patients are poorly represented in breast cancer research and guidelines do not provide evidence based recommendations for this specific group. We compared treatment strategies and survival outcomes between European countries and assessed whether variance in treatment patterns may be associated with variation in survival.MethodsPopulation-based study including patients aged ≥ 70 with non-metastatic BC from cancer registries from the Netherlands, Belgium, Ireland, England and Greater Poland. Proportions of local and systemic treatments, five-year relative survival and relative excess risks (RER) between countries were calculated.ResultsIn total, 236,015 patients were included. The proportion of stage I BC receiving endocrine therapy ranged from 19.6% (Netherlands) to 84.6% (Belgium). The proportion of stage III BC receiving no breast surgery varied between 22.0% (Belgium) and 50.8% (Ireland). For stage I BC, relative survival was lower in England compared with Belgium (RER 2.96, 95%CI 1.30–6.72, P < .001). For stage III BC, England, Ireland and Greater Poland showed significantly worse relative survival compared with Belgium.ConclusionsThere is substantial variation in treatment strategies and survival outcomes in elderly with BC in Europe. For early-stage BC, we observed large variation in endocrine therapy but no variation in relative survival, suggesting potential overtreatment. For advanced BC, we observed higher survival in countries with lower proportions of omission of surgery, suggesting potential undertreatment.

Five-Year Risk of Stroke after TIA or Minor Ischemic Stroke

BackgroundAfter a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events.MethodsWe evaluated patients who had had a TIA or minor stroke within 7 days before enrollment in the registry. Among 61 sites that participated in the 1-year outcome study, we selected 42 sites that had follow-up data on more than 50% of their enrolled patients at 5 years. The primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes (whichever occurred first), with an emphasis on events that occurred in the second through fifth years. In calculating the cumulative incidence of the primary outcome and secondary outcomes (except death from any cause), we treated death as a competing risk.ResultsA total of 3847 patients were included in the 5-year follow-up study; the median percentage of patients with 5-year follow-up data per center was 92.3% (interquartile range, 83.4 to 97.8). The composite primary outcome occurred in 469 patients (estimated cumulative rate, 12.9%; 95% confidence interval [CI], 11.8 to 14.1), with 235 events (50.1%) occurring in the second through fifth years. At 5 years, strokes had occurred in 345 patients (estimated cumulative rate, 9.5%; 95% CI, 8.5 to 10.5), with 149 of these patients (43.2%) having had a stroke during the second through fifth years. Rates of death from any cause, death from cardiovascular causes, intracranial hemorrhage, and major bleeding were 10.6%, 2.7%, 1.1%, and 1.5%, respectively, at 5 years. In multivariable analyses, ipsilateral large-artery atherosclerosis, cardioembolism, and a baseline ABCD2 score for the risk of stroke (range, 0 to 7, with higher scores indicating greater risk) of 4 or more were each associated with an increased risk of subsequent stroke.ConclusionsIn a follow-up to a 1-year study involving patients who had a TIA or minor stroke, the rate of cardiovascular events including stroke in a selected cohort was 6.4% in the first year and 6.4% in the second through fifth years. (Funded by AstraZeneca and others.)

Prognostic Factors in Anti-Neutrophil Cytoplasmic Antibody-Associated Glomerulonephritis with Severe Glomerular Sclerosis: A National Registry-Based Cohort Study.

Background Classification of patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) into histological classes is useful for predicting a patient's risk of progression to end-stage renal disease (ESRD). However, even in the worst prognostic group, the 5-year end-stage renal disease-free survival rate is as high as 50%. Objectives To investigate those prognostic factors indicative of progression to ESRD in patients with ANCA-GN and sclerosing histology. Methods Patients from the Norwegian Kidney Biopsy Registry between 1991 and 2012 who had biopsy verified pauci-immune glomerulonephritis, positive ANCA serology, and sclerosing histology were included. Cases with ESRD during follow-up were identified via linkage with the Norwegian Renal Registry. Potential prognostic factors with relevant cut-offs were compared in patients with and without progression to ESRD during follow-up. Results Of 23 included patients, 10 progressed to ESRD. ESRD patients had a lower initial estimated glomerular filtration rate (eGFR; 21 versus 52 ml/min/1.73 m2) and a lower percentage of normal glomeruli (4% versus 15%). Five-year risks of ESRD with eGFR >15 versus ≤15 ml/min/1.73 m2 were 77% and 15%, with percentage normal glomeruli >10% versus ≤10%, 83% and 39%. Conclusions eGFR and percentage of normal glomeruli are strong risk factors for ESRD in ANCA-GN with sclerosing histology.

Is Cardiorespiratory Fitness Related to Cardiometabolic Health and All-Cause Mortality Risk in Patients with Coronary Heart Disease? A CARE CR Study

BackgroundHigher cardiorespiratory fitness (CRF) is associated with lower morbidity and mortality in patients with coronary heart disease (CHD). The mechanisms for this are not fully understood. A more favourable cardiometabolic risk factor profile may be responsible; however, few studies have comprehensively evaluated cardiometabolic risk factors in relation to CRF amongst patients with CHD. We aimed to explore differences in cardiometabolic risk and 5-year all-cause mortality risk in patients with CHD who have low, moderate, and high levels of CRF.MethodsPatients with CHD underwent maximal cardiopulmonary exercise testing, echocardiogram, carotid intima-media thickness measurement, spirometry, and dual X-ray absorptiometry assessment. Full blood count, biochemical lipid profiles, high-sensitivity (hs) C-reactive protein, and NT-proBNP were analysed. Patients were defined as having low, moderate, or high CRF based on established prognostic thresholds.ResultsSeventy patients with CHD (age 63.1 ± 10.0 years, 86% male) were recruited. Patients with low CRF had a lower ventilatory anaerobic threshold, peak oxygen pulse, post-exercise heart rate recovery, and poor ventilatory efficiency. The low CRF group also had higher NT pro-BNP, hs-CRP, non-fasting glucose concentrations, and lower haemoglobin and haematocrit. Five-year mortality risk (CALIBER risk score) was also greatest in the lowest CRF group (14.9%).ConclusionsPractitioners should interpret low CRF as an important clinical risk factor associated with adverse cardiometabolic health and poor prognosis, study registry; www.researchregistry.com.

Dietary magnesium-to-iron intake ratios and risk of impaired fasting glucose in Chinese adults: The prospective Jiangsu Nutrition Study (JIN)

BackgroundStudies have consistently shown that risk of type 2 diabetes (T2D) is positively associated with dietary haem iron intake and inversely associated with dietary magnesium intake in a dose-response way. However, interaction effects of these two clinically important nutrients on T2DM risk in a prospective setting is unknown. ObjectiveTo determine the five-year risk of developing impaired fasting glucose (IFG) associated with dietary magnesium-to-iron intake ratios (Mg/Fe), including Mg/total Fe, Mg/haem-Fe and Mg/non-haem Fe. DesignA cohort study of 1056 participants recruited into the Jiangsu Nutrition Study (JIN) from 2002 to 2007, aged at least 20 years and without known diabetes and IFG at baseline were followed up for five years. Dietary magnesium and iron intake at baseline was assessed by 3-day weighed food records. Fasting plasma glucose was measured both at baseline and follow up. Logistic regression models were performed to determine the associations between quartiles (using bottom quartiles as referent categories) of magnesium to iron (including total Fe, haem-Fe and non-haem Fe) ratio and the risk of IFG (>5.6 mmol/L) adjusted for covariates: age, gender, body mass index (BMI), hypertension, serum ferritin, haemoglobin and family history of diabetes. ResultsThe mean (SD) intake of total Fe and magnesium was 25.0 (9.2) mg/d and 323 (125) mg/d. The incidence of IFG during 5-year follow up was 11.8%. Inverse associations were found between quartiles (Q) of Mg/haem-Fe and the risk of IFG in the fully adjusted model: odds ratios (OR) were 1.00, 0.59 (95%CI 0.35, 0.98), 0.49 (95%CI 0.28, 0.84), and 0.28 (95% CI 0.14, 0.55) (Q4), respectively. Weaker associations were found for quartiles of Mg/total Fe and no association was found between Mg/non-haem Fe and IFG risk. ConclusionsLow Mg/haem-Fe ratio is an independent risk factor for developing IFG in Chinese adults. Future research to determine the added predictive value of assessment of low dietary Mg/haem-Fe ratio beyond current T2D risk models in specific populations is justified.

Hip fracture risk in patients with alcoholic cirrhosis: A population-based study using English and Danish data

Cirrhosis, the prevalence of which is increasing, is a risk factor for osteoporosis and fractures. However, little is known of the actual risk of hip fractures in patients with alcoholic cirrhosis. Using linked primary and secondary care data from the English and Danish nationwide registries, we quantified the hip fracture risk in two national cohorts of patients with alcoholic cirrhosis. We followed 3,706 English and 17,779 Danish patients with a diagnosis of alcoholic cirrhosis, and we identified matched controls from the general populations. We estimated hazard ratios (HR) of hip fracture for patients vs. controls, adjusted for age, sex and comorbidity. The five-year hip fracture risk was raised both in England (2.9% vs. 0.8% for controls) and Denmark (4.6% vs. 0.9% for controls). With confounder adjustment, patients with cirrhosis had fivefold (adjusted HR 5.5; 95% CI 4.3-6.9), and 8.5-fold (adjusted HR 8.5; 95% CI 7.8-9.3) increased rates of hip fracture, in England and Denmark, respectively. This association between alcoholic cirrhosis and risk of hip fracture showed significant interaction with age (p <0.001), being stronger in younger age groups (under 45 years, HR 17.9 and 16.6 for English and Danish patients, respectively) than in patients over 75 years (HR 2.1 and 2.9, respectively). In patients with alcoholic cirrhosis, 30-day mortality following a hip fracture was 11.1% in England and 10.0% in Denmark, giving age-adjusted post-fracture mortality rate ratios of 2.8(95% CI 1.9-3.9) and 2.0(95% CI 1.5-2.7), respectively. Patients with alcoholic cirrhosis have a markedly increased risk of hip fracture and post-hip fracture mortality compared with the general population. These findings support the need for more effort towards fracture prevention in this population, to benefit individuals and reduce the societal burden. Alcoholic cirrhosis creates a large public health burden and is a risk factor for bone fractures. Based on data from England and Denmark, we found that hip fractures occur more than five times more frequently in people with alcoholic cirrhosis than in people without the disease. Additionally, the aftermath of the hip fracture is severe, such that up to 11% of patients with alcoholic cirrhosis die within 30 days after their hip fracture. These results suggest that efforts directed towards fracture prevention in people with alcoholic cirrhosis could be beneficial.

Rationale and Design of the SENECA (StEm cell iNjECtion in cAncer survivors) Trial

ObjectivesSENECA (StEm cell iNjECtion in cAncer survivors) is a phase I, randomized, double-blind, placebo-controlled study to evaluate the safety and feasibility of delivering allogeneic mesenchymal stromal cells (allo-MSCs) transendocardially in subjects with anthracycline-induced cardiomyopathy (AIC). BackgroundAIC is an incurable and often fatal syndrome, with a prognosis worse than that of ischemic or nonischemic cardiomyopathy. Recently, cell therapy with MSCs has emerged as a promising new approach to repair damaged myocardium. MethodsThe study population is 36 cancer survivors with a diagnosis of AIC, left ventricular (LV) ejection fraction ≤40%, and symptoms of heart failure (NYHA class II-III) on optimally-tolerated medical therapy. Subjects must be clinically free of cancer for at least two years with a ≤ 30% estimated five-year risk of recurrence. The first six subjects participated in an open-label, lead-in phase and received 100 million allo-MSCs; the remaining 30 will be randomized 1:1 to receive allo-MSCs or vehicle via 20 transendocardial injections. Efficacy measures (obtained at baseline, 6 months, and 12 months) include MRI evaluation of LV function, LV volumes, fibrosis, and scar burden; assessment of exercise tolerance (six-minute walk test) and quality of life (Minnesota Living with Heart Failure Questionnaire); clinical outcomes (MACE and cumulative days alive and out of hospital); and biomarkers of heart failure (NT-proBNP). ConclusionsThis is the first clinical trial using direct cardiac injection of cells for the treatment of AIC. If administration of allo-MSCs is found feasible and safe, SENECA will pave the way for larger phase II/III studies with therapeutic efficacy as the primary outcome.

A predictive model for recurrence in patients with glottic cancer implemented in a mobile application for Android

ObjectivesThe existing predictive models of laryngeal cancer recurrence present limitations for clinical practice. Therefore, we constructed, internally validated and implemented in a mobile application (Android) a new model based on a points system taking into account the internationally recommended statistical methodology. Materials and methodsThis longitudinal prospective study included 189 patients with glottic cancer in 2004–2016 in a Spanish region. The main variable was time-to-recurrence, and its potential predictors were: age, gender, TNM classification, stage, smoking, alcohol consumption, and histology. A points system was developed to predict five-year risk of recurrence based on a Cox model. This was validated internally by bootstrapping, determining discrimination (C-statistics) and calibration (smooth curves). ResultsA total of 77 patients presented recurrence (40.7%) in a mean follow-up period of 3.4 ± 3.0 years. The factors in the model were: age, lymph node stage, alcohol consumption and stage. Discrimination and calibration were satisfactory. ConclusionA points system was developed to obtain the probability of recurrence of laryngeal glottic cancer in five years, using five clinical variables. Our system should be validated externally in other geographical areas.

Long-term Outcomes of Follow-up for Initially Localised Clear Cell Renal Cell Carcinoma: RECUR Database Analysis

BackgroundOptimal follow-up (FU) strategy to detect potentially curable (PC) recurrences after treatment of localised clear cell renal cell carcinoma (ccRCC) is unclear. This study retrospectively analysed a large international database to determine recurrence patterns and overall survival (OS), as part of a wider project to issue recommendations on FU protocols. ObjectiveTo analyse associations between RCC recurrences in patients with ccRCC, their risk group stratifications, treatments, and subsequent outcomes. Design, setting, and participantsNonmetastatic ccRCC patients treated with curative intent between 1 January 2006 and 31 December 2011, with at least 4 yr of FU, were included. Patient, tumour and recurrence characteristics, Leibovich score, and management and survival data were recorded. Isolated local, solitary, and oligometastatic (three or fewer lesions at a single site) recurrences were considered PC, while all others were probably incurable (PI). InterventionPrimarily curative surgical treatment of ccRCC while at recurrence detection metastasectomy, systemic therapy, best supportive care, or observation. Outcome measurements and statistical analysisIncidence, time to recurrence (TTR), and OS were measured. Competing risk analysis, Kaplan-Meier, and Cox regression models were used. Results and limitationOf 1265 patients with ccRCC, 286 had a recurrence, with 131 being PC and 155 PI. Five-year cumulative risks of recurrence for low- (n=53), intermediate- (n=105), and high-risk (n=128) patients were, respectively, 7.2%, 23.2%, and 61.6%, of whom 52.8%, 37.1%, and 30.5% were PC, respectively. Median TTR was 25.0 for PC patients versus 17.3 mo for PI patients (p=0.004). Median OS was longer in PC compared with that in PI patients (p<0.001). Competing risk analysis showed highest risk of ccRCC-related death in younger and high-risk patients. Limitations were no data on comorbidities, retrospective cohort, and insufficient data excluding 12% of cohort. ConclusionsLow-risk group recurrences are rare and develop later. Treatment of recurrences with curative intent is disappointing, especially in high-risk patients. An age- and risk score-dependent FU approach is suggested. Patient summaryWe analysed data from eight European countries, and found that the incidence of the kidney cancer recurrence and patient survival correlated with clinical factors known to predict cancer recurrence reliably and age. We conclude that these factors should be used to design follow-up strategies.

Complex non atypical hyperplasia and the subsequent risk of carcinoma, atypia and hysterectomy during the following 9–14 years

IntroductionThe aim of this study was to evaluate the long-term risk of developing atypical hyperplasia/endometrial cancer or having a hysterectomy after being diagnosed with complex non-atypical hyperplasia (CH). Material and methodA historic cohort study of 114 women diagnosed with CH between January 1st 2000 and December 31st 2005. All patient records and pathologic reports were reviewed with complete follow up on all patients in the national pathologic database until September 1st 2014.Kaplan-Meier analysis was used to determine (1) no hysterectomy and (2) no diagnosis of endometrial cancer or atypia after the CH diagnosis. Results15% (n = 17) were diagnosed with endometrial cancer and 7% (n = 8) with atypia, most during the first year (10 cancer, 7 atypia). 9% (8/85) of the remaining women at risk developed cancer or atypia in the follow-up period after one year. By Kaplan-Meier the five-year risk for cancer or atypia was 20% (CI; 14–21). The risk of having undergone hysterectomy within five years was 30% (CI; 22–39). ConclusionThe long-term risk of being diagnosed with atypia or cancer after a CH diagnose is not insignificant, when disregarding patients having undergone hysterectomy. More than half the women with atypia or cancer are diagnosed or operated during the first year. This could indicate the presence of concomitant but unidentified cancer or atypia at the time of initial sampling. This study reinforces the importance of follow up or treatment of women with CH − especially, but not only during the first year. Key messageThe risk of having a hysterectomy or diagnosed with atypical hyperplasia/cancer endometrie is high after a diagnosis of complex hyperplasia without atypia.

The impact of patient age on breast cancer risk prediction models.

The impact of age on breast cancer risk model calculations at the population level has not been well documented. Retrospective analysis of formal breast cancer risk assessment in 36542 females ages 40-84 at a single institution from 02/2007 to 12/2009. Five-year and lifetime breast cancer risks were calculated using Gail, Tyrer-Cuzick version 6 (TC6), Tyrer-Cuzick version 7 (TC7), BRCAPRO, and Claus models. Risk of BRCA mutation was calculated using BRCAPRO, TC6, TC7, and Myriad. Eligibility for BRCA testing was assessed using NCCN guidelines. Descriptive analyses were performed and trends in risk were assessed by age. The lifetime risk of breast cancer trended down with increasing age in all risk models. TC7 calculated the highest estimates for lifetime risk for all age ranges and had the highest proportion of patients with a calculated lifetime risk >20%. Five-year risk increased with age in all models. By age 60-64, every risk model predicted a mean 5-year risk ≥1.7%. Myriad estimated >5% risk of BRCA mutation more often than other models for all ages. Risk of BRCA mutation stayed constant with age with Myriad, but trended down with increasing age with TC6, TC7, and BRCAPRO. More patients have an estimated lifetime risk of breast cancer >20% and qualify for MRI screening with the Tyrer-Cuzick model. All models predict an increased 5-year risk with age, which could impact chemoprevention recommendations. To maximize access to genetic testing, the Myriad model and NCCN guidelines should be used.

Evaluating Patients’ Own Health Perception in an Australian Rapid-Access Chest Pain Assessment Clinic Compared to Five-Year Absolute Cardiovascular Disease Risk

Evaluating Patients’ Own Health Perception in an Australian Rapid-Access Chest Pain Assessment Clinic Compared to Five-Year Absolute Cardiovascular Disease Risk

The Portuguese Registry of Hypertrophic Cardiomyopathy: Overall results

IntroductionWe report the results of the Portuguese Registry of Hypertrophic Cardiomyopathy, an initiative that reflects the current spectrum of cardiology centers throughout the territory of Portugal. MethodsA direct invitation to participate was sent to cardiology departments. Baseline and outcome data were collected. ResultsA total of 29 centers participated and 1042 patients were recruited. Four centers recruited 49% of the patients, of whom 59% were male, and mean age at diagnosis was 53±16 years. Hypertrophic cardiomyopathy (HCM) was identified as familial in 33%. The major reason for diagnosis was symptoms (53%). HCM was obstructive in 35% of cases and genetic testing was performed in 51%. Invasive septal reduction therapy was offered to 8% (23% of obstructive patients). Most patients (84%) had an estimated five-year risk of sudden death of <6%. Thirteen percent received an implantable cardioverter-defibrillator. After a median follow-up of 3.3 years (interquartile range [P25-P75] 1.3-6.5 years), 31% were asymptomatic. All-cause mortality was 1.19%/year and cardiovascular mortality 0.65%/year. The incidence of heart failure-related death was 0.25%/year, of sudden cardiac death 0.22%/year and of stroke-related death 0.04%/year. Heart failure-related death plus heart transplantation occurred in 0.27%/year and sudden cardiac death plus equivalents occurred in 0.53%/year. ConclusionsContemporary HCM in Portugal is characterized by relatively advanced age at diagnosis, and a high proportion of invasive treatment of obstructive forms. Long-term mortality is low; heart failure is the most common cause of death followed by sudden cardiac death. However, the burden of morbidity remains considerable, emphasizing the need for disease-specific treatments that impact the natural history of the disease.

Association between N-terminal Pro-Brain Natriuretic Peptide levels, glomerular filtration rate, and heart failure in the Multi-Ethnic Study of Atherosclerosis.

Background:This study examined the complementary prognostic role of NT-proBNP and eGFR for predicting heart failure (HF) in adults with and without chronic kidney disease (CKD) defined as eGFR<60 ml/min/1.73m2.Methods:We used data from the Multi-Ethnic Study of Atherosclerosis, a cohort of 6814 adults without baseline clinical cardiovascular disease. Five-year risk prediction of HF based on clinical HF risk variables (HFRV) plus NT-proBNP, eGFR or both was assessed using the C-statistic and the net reclassification index (NRI) after stratifying by CKD status.Results:Mean age at baseline was 62.3±10.3 years and CKD were present in 5.9%. A total of 39 and 180 HF events occurred in participants with and without CKD, respectively. Among adults with CKD, the C-statistic for HF risk prediction increased significantly (P =0.04) from 0.71 (95% CI 0.64, 0.78) with HFRV alone to 0.78 (95% CI 0.71, 0.85) with addition of NT-proBNP. In the non-CKD group, the C-statistic increased from 0.77 (95% CI 0.74, 0.80) with HFRV alone to 0.83 (95% CI 0.80, 0.85) with addition of NT-proBNP. Further addition of eGFR to the model did not alter the C-statistic regardless of CKD status. NRI improved by 23.1% and 10.2% in CKD and non-CKD, respectively, with the addition of NT-proBNP alone and findings were similar when both eGFR and NT-proBNP were both added to model.Conclusions:In adults without clinical cardiovascular disease, the addition of NT-proBNP but not eGFR to established HFRV improves HF risk prediction in adults with and without CKD.

Lithium Use, but Not Valproate Use, Is Associated With a Higher Risk of Chronic Kidney Disease in Older Adults With Mental Illness.

Lithium is an essential mood disorder treatment; however, it remains unclear whether lithium increases chronic kidney disease (CKD) risk. There are few data on this in the elderly, even though older adults may be particularly susceptible to CKD. We wished to determine whether lithium is associated with increased CKD risk relative to valproate in older adults. This nested case-control study analyzed province-wide administrative health data from mental health service users aged ≥ 66 years in Ontario, Canada, from 2003 to 2014. Five-year incident CKD risk was compared in lithium users, valproate users, and patients who used neither medication. ICD-10 was used to assign CKD diagnosis. We used conditional logistic regression to control for hypertension, diabetes mellitus, acute kidney injury, medications associated with lithium toxicity, and other potential confounders. 21,741 cases and 86,930 age- and sex-matched controls were identified, including 529 lithium users and 498 valproate users. After controlling for confounders, we found that lithium use was associated with increased risk of incident CKD (adjusted odds ratio [OR] = 1.76 [95% CI, 1.41-2.19]), while valproate use was not (adjusted OR = 1.03 [95% CI, 0.81-1.29]). Lithium is independently associated with an almost 2-fold increase in CKD risk in this community sample of older mental health service users. In the absence of clear information about certain contributing factors, such as inadequate monitoring and acute and chronic lithium level elevations, causes for this increase will need to be determined in future research.

A Point-based Mortality Prediction System for Older Adults with Diabetes

The mortality prediction models for the general diabetic population have been well established, but the corresponding elderly-specific model is still lacking. This study aims to develop a mortality prediction model for the elderly with diabetes. The data used for model establishment were derived from the nationwide adult health screening program in Taiwan in 2007–2010, from which we applied a 10-fold cross-validation method for model construction and internal validation. The external validation was tested on the MJ health screening database collected in 2004–2007. Multivariable Cox proportional hazards models were used to predict five-year mortality for diabetic patients ≥65 years. A total of 220,832 older subjects with diabetes were selected for model construction, of whom 23,241 (10.5%) died by the end of follow-up (December 31, 2011). The significant predictors retained in the final model included age, gender, smoking status, body mass index (BMI), fasting glucose, systolic and diastolic blood pressure, leukocyte count, liver and renal function, total cholesterol, hemoglobin, albumin, and uric acid. The Harrell’s C in the development, internal-, and external-validation datasets were 0.737, 0.746, and 0.685, respectively. We established an easy-to-use point-based model that could accurately predict five-year mortality risk in older adults with diabetes.

TCT-730 Five-year risk of target lesion revascularization in patients with and without an acute coronary syndrome treated with drug-eluting stents: a pooled analysis of individual participant data from three randomized SORT OUT trials

TCT-730 Five-year risk of target lesion revascularization in patients with and without an acute coronary syndrome treated with drug-eluting stents: a pooled analysis of individual participant data from three randomized SORT OUT trials

Risks of CIN 2+, CIN 3+, and Cancer by Cytology and Human Papillomavirus Status: The Foundation of Risk-Based Cervical Screening Guidelines.

The next round of the American Society for Colposcopy and Cervical Pathology (ASCCP)-sponsored cervical cancer screening and management guidelines will recommend clinical actions based on risk, rather than test-based algorithms. This article gives preliminary risk estimates for the screening setting, showing combinations of the 2 most important predictors, human papillomavirus (HPV) status and cytology result. Among 1,262,713 women aged 25 to 77 years co-tested with HC2 (Qiagen) and cytology at Kaiser Permanente Northern California, we estimated 0-5-year cumulative risk of cervical intraepithelial neoplasia (CIN) 2+, CIN 3+, and cancer for combinations of cytology (negative for intraepithelial lesion or malignancy [NILM], atypical squamous cells of undetermined significance [ASC-US], low-grade squamous intraepithelial lesion [LSIL], atypical squamous cells cannot exclude HSIL [ASC-H], high-grade squamous intraepithelial lesion [HSIL], atypical glandular cells [AGC]) and HPV status. Ninety percent of screened women had HPV-negative NILM and an extremely low risk of subsequent cancer. Five-year risks of CIN 3+ were lower after HPV negativity (0.12%) than after NILM (0.25%). Among HPV-negative women, 5-year risks for CIN 3+ were 0.10% for NILM, 0.44% for ASC-US, 1.8% for LSIL, 3.0% for ASC-H, 1.2% for AGC, and 29% for HSIL+ cytology (which was very rare). Among HPV-positive women, 5-year risks were 4.0% for NILM, 6.8% for ASC-US, 6.1% for LSIL, 28% for ASC-H, 30% for AGC, and 50% for HSIL+ cytology. As a foundation for the next guidelines revision, we confirmed with additional precision the risk estimates previously reported for combinations of HPV and cytology. Future analyses will estimate risks for women being followed in colposcopy clinic and posttreatment and will consider the role of risk modifiers such as age, HPV vaccine status, HPV type, and screening and treatment history.

Legacy Effect of Delayed Blood Pressure-Lowering Pharmacotherapy in Middle-Aged Individuals Stratified by Absolute Cardiovascular Disease Risk: Protocol for a Systematic Review.

BackgroundMany national and international guidelines recommend that the initiation of blood pressure (BP)-lowering drug treatment for the primary prevention of cardiovascular disease (CVD) should no longer be based on BP level alone, but on absolute cardiovascular risk. While BP-lowering drug treatment is beneficial in high-risk individuals at any level of elevated BP, clinicians are concerned about legacy effects on patients with low-to-moderate risk and mildly elevated BP who remain “untreated”.ObjectiveWe aim to investigate the legacy effect of delayed BP-lowering pharmacotherapy in middle-aged individuals (45-65 years) with mildly elevated BP (systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg) stratified by absolute risk for primary prevention of CVD, but particularly in the low-risk (<10% five-year absolute risk) group.MethodsRandomized trials of BP-lowering therapy versus placebo or pretreated subjects in active comparator studies with posttrial follow-up will be identified using a 2-step process. First, randomized trials of BP-lowering therapy will be identified by (1) retrieving the references of trials included in published systematic reviews of BP-lowering therapy, (2) retrieving studies published by the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC), and (3) checking studies referenced in the 1993 World Health Organization/International Society of Hypertension meeting memorandum on BP management. Posttrial follow-up studies will then be identified by forward citation searching the randomized trials identified in step 1 through Web of Science. The search will include randomized controlled trials with at least 1-year in-trial period and a posttrial follow-up phase. Age is the major determinant of absolute cardiovascular risk, so the participants in our review will be restricted to middle-aged adults who are more likely to have a lower cardiovascular risk profile. The primary outcome will be all-cause mortality. Secondary outcomes will include cardiovascular mortality, fatal stroke, fatal myocardial infarction, and death due to heart failure.ResultsThe searches for existing systematic reviews and BPLTTC studies were piloted and modified. The study is expected to be completed before June 2018.ConclusionsThe findings of this study will contribute to the body of knowledge concerning the beneficial, neutral, or harmful effects of delayed BP-lowering drug treatment on the primary prevention of CVD in patients with mildly elevated BP and low-to-moderate CVD risk.Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews: CRD42017058414; https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42017058414 (Archived by WebCite® at http://www.webcitation.org/6t6sa8O2Q)