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Objective: Long-term progression of peripheral arterial disease (PAD) as initial manifestation of atherosclerotic arterial disease is not well described. Cardiovascular (CV) risk was examined in different PAD populations diagnosed in a hospital setting in Sweden. Methods: Data for this retrospective cohort study were retrieved by linking data on morbidity, medication use, and mortality from Swedish national registries. Primary CV outcome was a composite of myocardial infarction, ischemic stroke (IS), and CV death. Kaplan-Meier analysis and Cox proportional hazards modeling was used for describing risk and relative risk. Results: Of 66,189 patients with an incident PAD diagnosis (2006-2013), 40,136 had primary PAD, 16,786 had PAD _ coronary heart disease (CHD), 5803 had PAD _IS, and 3464 had PAD _IS _CHD. One-year cumulative incidence rates of major CV events for the groups were 12%, 21%, 29%, and 34%, respectively. Corresponding numbers for 1-year all-cause death were 16%, 22%, 33%, and 35%. Compared with the primary PAD population, the relative risk increase for CV events was highest in patients with PAD _IS _CHD (hazard ratio [HR], 2.01), followed by PAD _IS (HR, 1.87) and PAD _ CHD (HR, 1.42). Despite being younger, the primary PAD population was less intensively treated with secondary preventive drug therapy. Conclusions: PAD as initial manifestation of atherosclerotic disease diagnosed in a hospital-based setting conferred a high risk: one in eight patients experienced a major CV event and one in six patients died within 1 year. Despite younger age and substantial risk of future major CV events, patients with primary PAD received less intensive secondary preventive drug therapy.

Radium-223 was minimally myelosuppressive. Multivariate analyses of data from ALSYMPCA patients identified baseline factors that may increase hematologic toxicity risk with radium-223. Extent of disease and degree of prostate-specific antigen elevation were predictive of grade 2-4 anemia; prior docetaxel, and decreased hemoglobin and platelets were predictive of grade 2-4 thrombocytopenia. Patients with these factors should be closely monitored during radium-223 therapy. Background: Myelosuppression is common in patients with progressive castration-resistant prostate cancer and bone metastases. Radium-223 prolongs overall survival in these patients but may cause myelosuppression; understanding risk factors will improve clinical decision making. We describe hematologic safety of radium-223 in ALSYMPCA and post hoc analyses identifying patients at increased risk for hematologic toxicity. Patients and Methods: Hematologic parameters and adverse events were analyzed. Multivariate analyses assessing baseline risk factors for hematologic toxicities were performed separately for radium-223 and placebo patients. Results: Nine hundred one patients received radium-223 (n = 600) or placebo (n = 301); 65% of radium-223 and 48% of placebo patients had the full 6 cycles. Grade 3/4 thrombocytopenia was more common in radium-223 versus placebo patients (6% vs. 2%). Logistic regression analyses identified significant baseline predictors for grade 2-4 hematologic toxicities related to radium-223 treatment: extent of disease (6-20 vs. < 6 bone metastases; odds ratio [OR] = 2.76; P = .022) and elevated prostate-specific antigen (OR = 1.65; P = .006) for anemia; prior docetaxel (OR = 2.16; P = .035), decreased hemoglobin (OR = 1.35; P = .008), and decreased platelets (OR = 1.44; P = .030) for thrombocytopenia. Neutropenia events were too few in placebo patients for a comparative analysis. There were no significant associations between hematologic toxicities and number of radium-223 i

Background In patients with type 2 diabetes and a high cardiovascular risk profile, the sodium-glucose co-transporter-2 (SGLT2) inhibitors empagliflozin and canagliflozin have been shown to lower cardiovascular morbidity and mortality. Using real-world data from clinical practice, we aimed to compare cardiovascular mortality and morbidity in new users of SGLT2 inhibitors versus new users of other glucose-lowering drugs, in a population with a broad cardiovascular risk profile. Methods CVD-REAL Nordic was an observational analysis of individual patient-level data from the Prescribed Drug Registers, Cause of Death Registers, and National Patient Registers in Denmark, Norway, and Sweden. All patients who filled a prescription for glucose-lowering drugs between 2012 and 2015 were included and followed up until Dec 31, 2015. Patients were divided into new users of SGLT2 inhibitors and new users of other glucose-lowering drugs. Each SGLT2 inhibitor user was matched with three users of other glucose-lowering drugs by use of propensity scores. Hazard ratios (HRs) were estimated by country (Cox survival model) and weighted averages were calculated. Cardiovascular outcomes investigated were cardiovascular mortality, major adverse cardiovascular events (cardiovascular mortality, myocardial infarction, and ischaemic or haemorrhagic stroke), hospital events for heart failure (inpatient or outpatient visit with a primary diagnosis of heart failure), non-fatal myocardial infarction, non-fatal stroke, and atrial fibrillation. We also assessed incidence of severe hypoglycaemia. Findings Matched SGLT2 inhibitor (n=22 830) and other glucose-lowering drug (n=68 490) groups were well balanced at baseline, with a mean follow-up of 0.9 (SD 4.1) years (80 669 patient-years) and mean age of 61 (12.0) years; 40% (36 362 of 91 320) were women and prevalence of cardiovascular disease was 25% (22 686 of 91 320). 94% of the total SGLT2 inhibitor exposure time was for use of dapagliflozin, with 5

Aims: To investigate the association of novel oral glucose-lowering drugs (GLDs), compared with that of insulin, with risk of all-cause mortality, cardiovascular disease (CVD) and severe hypoglycaemia. Methods: During 2013 to 2014 all patients with type 2 diabetes in Sweden identified as new users of novel oral GLDs, either dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter-2 (SGLT2) inhibitors (only dapagliflozin available in Sweden during the study period), with those initiating insulin as a comparison group, in the Prescribed Drug Register were included and followed in the Patient and Cause of Death Registers. The novel GLD group and insulin group were matched 1: 1 using propensity score. Cox regression models were used to estimate risks. Results: Of 37 603 patients, 21 758 were matched 1: 1 to novel GLD vs insulin groups, with median follow-up times of 1.51 years (16 304 patient-years) and 1.53 years (16 306 patientyears), respectively. Treatment with novel GLDs was associated with a 44% (hazard ratio [HR] 0.56 [95% confidence interval {CI} 0.49-0.64]), 15% (HR 0.85 [95% CI 0.73-0.99]) and 74% (0.26 [95% CI 0.12-0.57]) lower risk of all-cause mortality, CVD and hypoglycaemia, respectively, compared with insulin treatment. In separate analyses for the two novel GLDs, dapagliflozin was associated with lower risks of all-cause mortality and CVD (56% [HR 0.44, 95% CI 0.28-0.70] and 49% [HR 0.51, 95% CI 0.30-0.86], respectively), while DPP-4 inhibitor treatment was associated with lower risk of all-cause mortality (41% [HR 0.59, 95% CI 0.51-0.67]), but not with CVD (HR 0.87, 95% CI 0.75-1.01). Conclusions: Novel oral GLD treatment was associated with lower risk of all-cause mortality, CVD and severe hypoglycaemia compared with insulin treatment. Dapagliflozin was associated with a lower risk of both all-cause mortality and CVD, whereas DPP-4 inhibitor treatment was only associated with lower risk of all-cause mortality., Title in WOS: Novel oral glucose-lowering drugs are associated with lower risk of all-cause mortality, cardiovascular events and severe hypoglycaemia compared with insulin in patients with type 2 diabetese

Aims: The objective of this nationwide study was to compare the risk of all-cause mortality, fatal and nonfatal cardiovascular disease (CVD), and severe hypoglycemia in patients with type 2 diabetes (T2D) on metformin monotherapy treatment starting second-line treatment with either insulin or dipeptidyl peptidase-4 inhibitor (DPP-4i). Methods: All patients with T2D in Sweden who initiated second-line treatment with insulin or DPP-4i after metformin monotherapy during 2007-2014 identified in the Swedish Prescribed Drug Register were followed for outcome in the Cause of Death and National Patient Registers. Insulin and DPP-4i patients were matched 1: 1 using propensity-score matching. Comparisons between groups were performed using unadjusted Cox regression models. Additionally, multivariate adjusted survival models were used to test the results using the full population without matching. Results: Of 27,767 mono-metformin-treated patients, 55.7% started insulin and 44.3% a DPP-4i, and after matching both groups had 9278 patients each. Median follow-up (patients years) times were 3.84 (37,578) and 3.93 (37,983) for insulin and DPP-4i-groups, respectively. Insulin compared with DPP-4i was associated with higher risk of subsequent all-cause mortality, fatal and nonfatal CVD, and severe hypoglycemia; adjusted HR (95% CI): 1.69 (1.45-1.96); 1.39 (1.21-1.61); and 4.35 (2.26-8.35), respectively. When performing multivariate adjusted analyses on the full population similar results were found. Conclusions: Initiation of insulin, compared with DPP-4i treatment, was associated with an increased risk of subsequent all-cause mortality, fatal and nonfatal CVD, and severe hypoglycemia. Results from randomized trials will be important to elucidate causal relationships.

Objectives The aims of this population based study were to describe mid- to long-term amputation risk, cumulative incidence of death or amputation, and differences in pre-operative comorbidities in patients revascularised for lower limb peripheral artery disease (PAD). Methods This was an observational cohort study. Data from the Swedish National Quality Registry for Vascular Surgery (Swedvasc) were combined with mandatory national health care registries and patient medical records. All patients who underwent revascularisation in Sweden between May 2008 and May 2013 for intermittent claudication (IC) or critical limb ischaemia(CLI), aged 50 years and older, were identified through the Swedvasc database. The mandatory national health care registries and medical records provided data on comorbidities, mortality, and major amputations. Results A total of 16,889 patients with PAD (IC, n = 6272; CLI, n = 10,617) were studied. The incidence of amputations in IC patients was 0.4% (range 0.3%–0.5%) per year. Among CLI patients, the amputation rate during the first 6 months following revascularisation was 12.0% (95% CI 11.3–12.6). Thereafter, the incidence declined to approximately 2% per year. The cumulative combined incidence of death or amputation 3 years after revascularisation was 12.9% (95% CI 12.0–13.9) in IC patients and 48.8% (95% CI 47.7–49.8) in CLI patients. Among CLI patients, compared with IC patients, the prevalence of diabetes, ischaemic stroke, heart failure, and atrial fibrillation was approximately doubled and renal failure was nearly tripled, even after age standardisation. Conclusion The risk of amputation is particularly high during the first 6 months following revascularisation for CLI. IC patients have a benign course in terms of limb loss. Mortality in both IC and CLI patients is substantial. Revascularised CLI patients have different comorbidities from IC patients., Funding Agencies|AstraZeneca; Futurum Academy for Health and Care, Region Jonkoping County, Sweden

Aims: There are safety concerns related to sulphonylurea treatment. The objective of this nationwide study was to compare the risk of cardiovascular disease (CVD), all-cause mortality and severe hypoglycemia in patients with type 2 diabetes (T2D) starting second-line treatment with either metformin + sulphonylurea or metformin + dipeptidyl peptidase-4 inhibitor (DPP-4i). Methods: All patients with T2D in Sweden who initiated second-line treatment with metformin + sulphonylurea or metformin + DPP-4i during 2006-2013 (n = 40,736 and 12,024, respectively) were identified in this nationwide study. The Swedish Prescribed Drug Register and the Cause of Death and National Patient Registers were used, and Cox survival models adjusted for age, sex, fragility, prior CVD, and CVD-preventing drugs were applied to estimate risks of events. Propensity score adjustments and matching methods were used to test the results. Results: Of 52,760 patients; 77% started metformin + SU and 23% metformin + DPP-4i. Crude incidences for severe hypoglycemia, CVD, and all-cause mortality in the SU cohort were 2.0, 19.6, and 24.6 per 1000 patient-years and in the DPP-4i cohort were 0.8, 7.6, and 14.9 per 1000 patient-years, respectively. Sulphonylurea compared with DPP4i was associated with higher risk of subsequent severe hypoglycemia, fatal and nonfatal CVD, and all-cause mortality; adjusted HR (95% CI): 2.07 (1.11-3.86); 1.17 (1.01-1.37); and 1.25 (1.02-1.54), respectively. Results were confirmed by additional propensity-adjusted and matched analyses. Among the SU drugs, glibenclamide had the highest risks. Conclusions: Metformin + SU treatment was associated with an increased risk of subsequent severe hypoglycemia, cardiovascular events, and all-cause mortality compared with metformin + DPP4i. Results from randomized trials will be important to elucidate causal relationships.

Aims To assess the international validity of using hospital record data to compare long-term outcomes in heart attack survivors. Methods and results We used samples of national, ongoing, unselected record sources to assess three outcomes: cause death; a composite of myocardial infarction (MI), stroke, and all-cause death; and hospitalized bleeding. Patients aged 65 years and older entered the study 1 year following the most recent discharge for acute MI in 2002–11 [n = 54 841 (Sweden), 53 909 (USA), 4653 (England), and 961 (France)]. Across each of the four countries, we found consistent associations with 12 baseline prognostic factors and each of the three outcomes. In each country, we observed high 3-year crude cumulative risks of all-cause death (from 19.6% [England] to 30.2% [USA]); the composite of MI, stroke, or death [from 26.0% (France) to 36.2% (USA)]; and hospitalized bleeding [from 3.1% (France) to 5.3% (USA)]. After adjustments for baseline risk factors, risks were similar across all countries [relative risks (RRs) compared with Sweden not statistically significant], but higher in the USA for all-cause death [RR USA vs. Sweden, 1.14 (95% confidence interval 1.04–1.26)] and hospitalized bleeding [RR USA vs. Sweden, 1.54 (1.21–1.96)]. Conclusion The validity of using hospital record data is supported by the consistency of estimates across four countries of a high adjusted risk of death, further MI, and stroke in the chronic phase after MI. The possibility that adjusted risks of mortality and bleeding are higher in the USA warrants further study.

Objective: Peripheral artery disease (PAD) is common worldwide, and PAD patients are increasingly offered lower limb revascularization procedures. The aim of this population-based study was to describe the current risk for cardiovascular (CV) events and mortality and also to elucidate the current pharmacologic treatment patterns in revascularized lower limb PAD patients. Methods: This observational, retrospective cohort study analyzed prospectively collected linked data retrieved from mandatory Swedish national health care registries. The Swedish National Registry for Vascular Surgery database was used to identify revascularized PAD patients. Current risk for CV events and death was analyzed, as were prescribed drugs aimed for secondary prevention. A Cox proportional hazard regression model was used to explore risk factors for suffering a CV event. Results: Between May 2008 and December 2013, there were 18,742 revascularized PAD patients identified. Mean age was 70.0 years among patients with intermittent claudication (IC; n = 6959) and 76.8 years among patients with critical limb ischemia (CLI; n = 11,783). Antiplatelet therapy, statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and beta-blockers were used by 73%, 60%, 57%, and 49% at admission for revascularization. CV event rate (a composite of myocardial infarction, ischemic stroke, or CV death) at 12, 24, and 36 months was 5.1% (95% confidence interval [CI], 4.5-5.6), 9.5% (95% CI, 8.7-10.3), and 13.8% (95% CI, 12.8-14.8) in patients with IC and 16.8% (95% CI, 16.1-17.6), 25.9% (95% CI, 25.0-26.8), and 34.3% (95% CI, 33.2-35.4) in patients with CLI. Best medical treatment, defined as any antiplatelet or anticoagulant therapy along with statin treatment, was offered to 65% of IC patients and 45% of CLI patients with little change during the study period. Statin therapy was associated with reduced CV events (hazard ratio, 0.76; 95% CI, 0.71-0.81; P < .001), whereas treatment with

Aims Long-term contemporary nationwide data on resource use and healthcare costs after myocardial infarction (MI) in a clinical practice setting are not widely studied, and the aim of this study was to investigate resource use patterns and healthcare costs in patients with MI in a nationwide clinical practice setting. Methods and results This retrospective cohort study included all patients identified in the compulsory Swedish nationwide patient register with a diagnosis of MI between 1 July 2006 and 30 June 2011. Cardiovascular hospitalization and outpatient visits data from the patient register were combined with data from the cause of death register and the drug utilization register. For a subset of patients, data were also available from a primary care register. Healthcare resource use patterns and annual costs [reported in 2014 euros (€) converted from Swedish kronor (SEK) using the exchange rate €1 = SEK 9.33)] were estimated for the year prior to the occurrence of MI as well as for a maximum follow-up period of 6 years post-MI. The study included 97 252 patients with a diagnosis of MI with a total number of 285 351 observation years. The majority of healthcare consumption occurred within the first year of MI where patients were on average hospitalized 1.55 times, made 1.08 outpatient care visits, and 3.80 primary care visits. In the long term, for the majority of resource use categories, average consumption was higher in the years after MI compared with the year prior to MI. Healthcare costs at 6 years of follow-up were approximately €20 000 of which €12 460 occurred in the first year, and the major part was attributed to hospitalizations. Conclusion For patients with 6 years of follow-up after MI, healthcare costs were approximately €20 000. The major part of costs occurred in the first year after MI and was driven by hospitalizations

Objectives: The aim of this study was to evaluate the diagnostic accuracy of sensitivity and specificity of cervical lesions by the low-cost, portable Gynocular colposcope and a stationary colposcope, in women referred for colposcopy with abnormal cervical cytology. Methods: A randomized cross-over clinical trial for evaluating the diagnostic accuracy in detecting cervical lesions by the Gynocular and a stationary colposcope. The Swede score systematic colposcopy system was used for evaluation of colposcopic abnormalities. Directed punch biopsy and excisional cone biopsy were used as the gold-standard by histologically confirmed high grade cervical lesions CIN2+ (CIN2, CIN3, CIN3+). In total, 123 women referred for colposcopy due to abnormal cervical cytology were recruited at the Department of Obstetrics and Gynecology, Danderyd Hospital, Stockholm, Sweden. The percentage agreement and the kappa statistic were calculated for Swede score by the Gynocular and a stationary colposcope. Swede scores were compared with the results from directed punch biopsy and excisional cone biopsy. Results: The Gynocular and the stationary colposcope had a high agreement of Swede scores with a Kappa statistic of 0.947, p < .0001. Punch biopsy diagnosed CIN2+ (CIN2, CIN3, and invasive cancer) in 44 (35.7 percent) women while cytology detected CIN2+ in 34 (27.6 percent) women. There were no significant differences of the sensitivity and specificity for different Swede scores by the Gynocular or a stationary colposcope in detecting CIN 2+. Conclusions: There were no significant differences in sensitivity or specificity in detecting cervical lesions by the Gynocular or stationary colposcope. The Gynocular is as accurate in diagnosing cervical lesions as a stationary colposcope.

Background & Aims: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease in pregnancy. It is associated with hepatobiliary diseases that might predispose to cancer and also with gestational diabetes and preeclampsia. In this study, we examined associations between ICP and cancer, and immune-mediated and cardiovascular diseases. Methods: By linking the Swedish Medical Birth Register and the Swedish Patient Register, we identified 11,388 women with ICP and 113,893 matched women without ICP who gave birth between 1973 and 2009. Diagnoses of cancer and immune-mediated and cardiovascular diseases both before and after delivery were obtained from the Patient Register. The main outcome measures were hazard ratios (HRs), calculated through Cox regression, for the indicated diseases after delivery. Results: ICP was not associated with later overall cancer (HR 1.07, 95% confidence interval [CI] 0.94-1.21), but it was associated with later liver and biliary tree cancer (HR 3.61, 95% CI 1.68-7.77, and 2.62, 95% CI 1.26-5.46, respectively). ICP was also associated with later immune-mediated diseases (HR 1.28, 95% CI 1.19-1.38), and specifically diabetes mellitus (HR 1.47, 95% CI 1.26-1.72), thyroid disease (HR 1.30, 95% CI 1.14-1.47), psoriasis (HR 1.27, 95% CI 1.07-1.51), inflammatory polyarthropathies (HR 1.32, 95% CI 1.11-1.58) and Crohn's disease (HR 1.55, 95% CI 1.14-2.10), but not ulcerative colitis (HR 1.21, 95% CI 0.93-1.58). Women with ICP also had a small increased risk of later cardiovascular disease (HR 1.12, 95% CI 1.06-1.19). Conclusions: Women with ICP have increased risk of later hepatobiliary cancer and immune-mediated and cardiovascular diseases. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.