Familial hypercholesterolaemia in UK primary care: a Clinical Practice Research Datalink study of an under-recognised condition.

BACKGROUND: Studies utilising genotyping methods report the prevalence of familial hypercholesterolaemia to be as high as one in 137 of the adult population. AIM: To estimate the prevalence of familial hypercholesterolaemia measured by clinically coded diagnosis, associated treatments, and lipid measurements observed in UK primary care. DESIGN AND SETTING: This was a retrospective analysis using the Clinical Practice Research Datalink (CPRD) GOLD database. METHOD: Patients aged ≥18 years and actively registered on the index date (30 June 2018) formed the study cohort. Point prevalence of familial hypercholesterolaemia for 2018 was estimated overall and for each nation of the UK. Patients with familial hypercholesterolaemia were stratified into primary and secondary prevention groups, defined as those with/without a prior diagnosis of atherosclerotic cardiovascular disease. Prevalence estimates and extrapolations were replicated for these subgroups. Baseline demographic, lipid, and clinical characteristics for the prevalent cohort were presented. RESULTS: In total, 4048 patients with familial hypercholesterolaemia formed the study cohort. The estimated familial hypercholesterolaemia prevalence for the UK was 16.4 per 10 000 (95% confidence interval [CI] = 16.0 to 16.9). Of these, 2646 (65.4%) patients with familial hypercholesterolaemia had a recent prescription for lipid-lowering therapy. Mean lipid levels were lower for those treated with lipid-lowering therapy compared with those untreated: 5.34 mmol/L (SD 1.50) versus 6.25 mmol/L (SD 1.55) for total cholesterol and 3.15 mmol/L (SD 1.34) versus 3.96 mmol/L (SD 1.36) for low-level density lipoprotein cholesterol. CONCLUSION: The estimated prevalence of familial hypercholesterolaemia was one in 608 of the population, less than expected from other studies, which may indicate that familial hypercholesterolaemia is under-recognised in UK primary care. Over one-third of diagnosed patients were undertreated and many did not achieve target goals, placing them at risk of cardiovascular events.

What is the actual relationship between neutrophil extracellular traps and COVID-19 severity? A longitudinal study.

BACKGROUND: Neutrophil extracellular traps (NETs) have repeatedly been related to COVID-19 severity and mortality. However, there is no consensus on their quantification, and there are scarce data on their evolution during the disease. We studied circulating NET markers in patients with COVID-19 throughout their hospitalization. METHODS: We prospectively included 93 patients (201 blood samples), evaluating the disease severity in 3 evolutionary phases (viral, early, and late inflammation). Of these, 72 had 180 samples in various phases. We also evaluated 55 controls with similar age, sex and comorbidities. We measured 4 NET markers in serum: cfDNA, CitH3, and MPO-DNA and NE-DNA complexes; as well as neutrophil-related cytokines IL-8 and G-CSF. RESULTS: The COVID-19 group had higher CitH3 (28.29 vs 20.29 pg/mL, p = 0.022), and cfDNA, MPO-DNA, and NE-DNA (7.87 vs 2.56 ng/mL; 0.80 vs 0.52 and 1.04 vs 0.72, respectively, p < 0.001 for all) than the controls throughout hospitalisation. cfDNA was the only NET marker clearly related to severity, and it remained higher in non-survivors during the 3 phases. Only cfDNA was an independent risk factor for mortality and need for intensive care. Neutrophil count, IL-8, and G-CSF were significantly related to severity. MPO-DNA and NE-DNA showed significant correlations (r: 0.483, p < 0.001), including all 3 phases and across all severity grades, and they only remained significantly higher on days 10-16 of evolution in those who died. Correlations among the other NET markers were lower than expected. CONCLUSIONS: The circulating biomarkers of NETs were present in patients with COVID-19 throughout hospitalization. cfDNA was associated with severity and mortality, but the three other markers showed little or no association with these outcomes. Neutrophil activity and neutrophil count were also associated with severity. MPO-DNA and NE-DNA better reflected NET formation. cfDNA appeared to be more associated with overall tissue damage; previous widespread use of this marker could have overestimated the relationship between NETs and severity. Currently, there are limitations to accurate NET markers measurement that make it difficult to assess its true role in COVID-19 pathogenesis.

Clinical characteristics and treatment patterns in patients with atherosclerotic cardiovascular disease with hypercholesterolemia: a retrospective analysis of a large US real-world database cohort.

OBJECTIVE: Guidelines developed by the American College of Cardiology/American Heart Association (ACC/AHA) recommend lipid-lowering therapies (LLTs) to reduce low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD) risk. This study described LLT utilization patterns and LDL-C goal achievement (to <70 mg/dL) among patients with ASCVD in the United States. METHODS: This retrospective study was conducted using Optum's de-identified Clinformatics Data Mart Database (CDM). Patients with their first ASCVD diagnosis (index date) in the CDM database between July 1, 2015, and December 31, 2018, were followed for ≥12 months to assess LLT utilization patterns and change in LDL-C. LLTs included were statins and non-statin LLTs (ezetimibe, fibrates, and proprotein convertase subtilisin/kexin type 9 inhibitors). Adherence was measured as the proportion of days covered (PDC), defined as the number of days with drug on-hand (or number of days exposed to drug) divided by the 12-month follow-up period. Patients with PDC ≥0.8 were considered adherent. RESULTS: Among the patients with ASCVD (N = 1,424,893) included in this study, only 621,978 (43.7%) had at least one LDL-C measurement at baseline (6 months prior to and 3 months after the index date). The mean age was 71.5 years, and almost half of the patients were female. Patients were followed for a mean (standard deviation [SD]) duration of 30.6 (11.4) months (median of 29.9 months). During the follow-up, about one-quarter of the patients did not receive any LLT. Among treated patients, 89.5% received statins and 10.5% received non-statin LLT. Less than half (47.6%) of the patients were adherent to the index treatment during the 12-month follow-up. Even in patients receiving combination therapy (statin + non-statin LLT), a sizable proportion (35.8%) showed an increase in LDL-C over the follow-up period. CONCLUSIONS: This retrospective study highlighted limited LDL-C monitoring in patients with ASCVD, and unmet need in terms of suboptimal utilization of non-stain LLTs, limited adherence to LLTs, and inadequate lipid control after treatment (among those with LDL-C measurements during the follow-up period) need to be addressed to improve outcomes in this patient cohort.

International societies of cardiologists recommend use of medications to lower the "bad" cholesterol, and its risk of cardiovascular diseases like stroke. We aimed to describe how those medications are being used and to what extent patients with cardiovascular diseases in the United States have their "bad" cholesterol under control. Results of this study indicate that cholesterol check-up among the patients was limited. Among recommended medications, statins were mostly used, whereas use of other recently approved medications was minimal. One-quarter of patients were not prescribed medications to control their cholesterol. Moreover, patients were not taking the medications as frequently as prescribed.

Risk of major adverse cardiovascular events associated with elevated low-density lipoprotein cholesterol in a population with atherosclerotic cardiovascular disease with and without type 2 diabetes: a UK database analysis using the Clinical Practice Research Datalink.

OBJECTIVES: To estimate the 12-month probabilities of major adverse cardiovascular events (MACE) and non-cardiovascular death in patients with atherosclerotic cardiovascular disease (ASCVD) and elevated low-density lipoprotein cholesterol (LDL-C). DESIGN: A retrospective database analysis. SETTING: UK primary care. PARTICIPANTS: Patients were selected from the Clinical Practice Research Datalink (Aurum) linked to Hospital Episode Statistics inpatient and Office of National Statistics mortality datasets. Patients with an ASCVD diagnosis between 01 January 2010 and 31 May 2018 and LDL-C ≥2.6 mmol/L were selected. PRIMARY OUTCOMES: Primary outcomes were 12-month risk of (1) MACE (composite of revascularisation, unstable angina, non-fatal myocardial infarction, non-fatal stroke and cardiovascular death) and (2) non-cardiovascular mortality. Kaplan-Meier survival analysis estimated the probability of each outcome. A Cox proportional hazards model explored covariates associated with MACE. RESULTS: Of 102 245 study patients, 16 501 (16.1%) had a diagnosis of type 2 diabetes (T2DM). 65.5% of those with and 49.9% of those without T2DM had a lipid-lowering therapy (LLT) 6 months prior to index diagnosis. Twelve-month probability of MACE was 7.9% for non-T2DM and 11.8% for T2DM. LDL-C was significantly associated with risk of MACE (HR=1.19 (95% CI 1.16 to 1.22) per 1 mmol/L). History of acute coronary syndrome, other coronary heart disease, stroke and T2DM significantly increased the risk of MACE. Ezetimibe (0.88 (95% CI 0.79 to 0.99)) and low-intensity statins (0.88 (95% CI 0.79 to 0.97)) were associated with reduced 12-month MACE risk.and low-intensity statins 0.88 (95% CI 0.79 to 0.97) CONCLUSION: We confirmed the association between elevated LDL-C and MACE. Many patients with ASCVD and elevated LDL-C were untreated with LLT. With the increasing demands on general practitioners, initiatives aimed at improving identification and treatment of at-risk patients within primary care should be considered.

IL-6 and cfDNA monitoring throughout COVID-19 hospitalization are accurate markers of its outcomes.

BACKGROUND: Severe COVID-19 entails a dysregulated immune response, most likely inflammation related to a lack of virus control. A better understanding of immune toxicity, immunosuppression balance, and COVID-19 assessments could help determine whether different clinical presentations are driven by specific types of immune responses. The progression of the immune response and tissular damage could predict outcomes and may help in the management of patients. METHODS: We collected 201 serum samples from 93 hospitalised patients classified as moderately, severely, and critically ill. We differentiated the viral, early inflammatory, and late inflammatory phases and included 72 patients with 180 samples in separate stages for longitudinal study and 55 controls. We studied selected cytokines, P-selectin, and the tissue damage markers lactate dehydrogenase (LDH) and cell-free DNA (cfDNA). RESULTS: TNF-α, IL-6, IL-8, and G-CSF were associated with severity and mortality, but only IL-6 increased since admission in the critical patients and non-survivors, correlating with damage markers. The lack of a significant decrease in IL-6 levels in the critical patients and non-survivors in the early inflammatory phase (a decreased presence in the other patients) suggests that these patients did not achieve viral control on days 10-16. For all patients, lactate dehydrogenase and cfDNA levels increased with severity, and cfDNA levels increased in the non-survivors from the first sample (p = 0.002) to the late inflammatory phase (p = 0.031). In the multivariate study, cfDNA was an independent risk factor for mortality and ICU admission. CONCLUSIONS: The distinct progression of IL-6 levels in the course of the disease, especially on days 10-16, was a good marker of progression to critical status and mortality and could guide the start of IL-6 blockade. cfDNA was an accurate marker of severity and mortality from admission and throughout COVID-19 progression.

Recurrent heart failure hospitalizations increase the risk of mortality in heart failure patients with atrial fibrillation and type 2 diabetes mellitus in the United Kingdom: a retrospective analysis of Clinical Practice Research Datalink database.

BACKGROUND: Heart failure (HF) is a global illness and is a leading cause of hospitalizations. Recurrent HF hospitalization (HFH) is associated with increased risk of cardiovascular (CV) and all-cause mortality, thereby burdening the health system. Type 2 diabetes mellitus (T2DM) and atrial fibrillation (AF) are two important comorbidities in patients living with HF. This study aims to assess the association between recurrent HFHs with CV and all-cause mortality in patients living with HF and having AF and/or T2DM. METHODS: This study was conducted using primary care data from the Clinical Practice Research Datalink database with linkage to hospital data and mortality data. Adults living with HF and with at least 1 HFH were identified from January 2010 to December 2014. Patients were grouped based on the number of recurrent HFHs. During follow-up, all-cause mortality or CV mortality for the HF population with AF and T2DM was recorded. RESULTS: Overall, 32.9% of 2344 T2DM patients and 28.2% of 4585 AF patients had at least 1 recurrent HFH. The patients were relatively elderly and were predominantly male. The mean number of all-cause hospitalizations in HF patients having T2DM and AF, with ≥ 1 recurrent HFH were significantly higher than patients without recurrent HFH. The annualized mortality rates in CV mortality as the primary cause and for all-cause mortality and increased with recurrent HFHs, in T2DM and AF patients. The risk of CV mortality as primary cause and all cause morality were 5.39 and 3.19 times higher in T2DM patients with 3 recurrent HFHs versus no recurrent HFH. Similarly, the risk of CV mortality as primary cause and all cause morality was 5.98 and 4.3 times higher in AF patients with 3 recurrent HFHs versus those with no recurrent HFH. CONCLUSIONS: Recurrent HFHs are strongly associated with CV mortality and all-cause mortality in HF patients with TD2M or AF. The hospitalization rate highlights the need for treatment and disease management, which will improve the course of the disease and help patients stay out of hospital.

Burden and Quality of Life Among Female and Male Patients with Heart Failure in Europe: A Real-World Cross-Sectional Study.

PURPOSE: To characterize symptoms, clinical burden, and health-related quality of life (HRQoL) among women and men with heart failure (HF) with a left ventricular ejection fraction (LVEF) of ≤60% in Europe. PATIENTS AND METHODS: A real-world cross-sectional study was conducted in France, Germany, Italy, Spain, and United Kingdom from June to November 2019. Patient record forms were completed by 257 cardiologists and 158 general practitioners for consecutive patients with HF. The same patients were invited to complete a questionnaire comprising patient-reported outcomes: the Minnesota Living with Heart Failure Questionnaire (MLHFQ), five-level five-dimension EuroQol questionnaire (EQ-5D-5L), Visual Analogue Scale (VAS), and Work Productivity and Activity Impairment questionnaire. RESULTS: The mean age of 804 patients (men, n=517; women, n=287) was 68.6 years (men, 67.8 years; women, 70.2 years; p=0.0022). The mean LVEF was 44.7% (men, 43.6%; women, 46.8%; p<0.0001). Patients reported dyspnoea when active (overall, 55.7%; men, 56.0%; women, 55.3%), fatigue/weakness/faintness (34.5%; men, 32.9%; women, 37.2%), and oedema (20.3%; men, 18.7%; women, 23.1%) as the most troublesome HF symptoms. Overall, 54.1% of patients reported low mood/depression (men, 50.8%; women, 60.1%). The overall MLHFQ mean score was higher (ie, poorer HRQoL) among women vs men (37.9 vs 34.6; p=0.0481). MLHFQ was consistently higher (ie, poorer HRQoL) for women vs men across the physical (18.6 vs 16.6; p=0.0041) and emotional (9.4 vs 7.9; p=0.0021) scoring domains. Mean EQ-5D utility (0.69 vs 0.75; p=0.0046) and VAS scores (55.4 vs 61.3; p<0.0001) were lower among women compared with men. Overall, 23.4% of patients were hospitalized owing to HF in the previous year (men, 22.7%; women, 24.6%). Patients reported 43.2% activity impairment due to HF (men, 41.6%; women, 46.4%; p=0.01). CONCLUSION: HF causes a substantial burden on patients, with a greater burden among women vs men. This gender-related difference is consistent with other HF studies, warranting further research to understand the underlying reasons.

Comparative study of two immunoassays used for the determination of serum vitamin D.

OBJECTIVES: The best indicator of vitamin D level is the determination of serum 25-hydroxyvitamin D (25(OH)D). Due to the lack of standardization of the available methods, there are problems of precision and reproducibility in its measurement. The objective of this study was to compare the results of 25(OH)D concentration determined by two different immunoassay methods. DESIGN: and Methods: 25(OH)D was analyzed in 184 serum samples in an IDS-iSYS Multi-Discipline Automated System Analyzer (Vitro) and in an Alinity i automated Analyzer (Abbott). Then, results were compared. Three groups were considered: group of total patients, group with vitamin D supplements and group without treatment. RESULTS: Of the total patients, 52.7% received vitamin D supplements. The correlation coefficient of agreement for general group, supplementation group and group without supplementation was 0.92, 0.91 and 0.89, respectively. In all of them, a kappa index>0.75 was obtained. CONCLUSIONS: The assays evaluated are not comparable to each other. Despite this, they show an excellent concordance in the evaluation of the vitamin D status.

External validation of a claims-based model to predict left ventricular ejection fraction class in patients with heart failure.

BACKGROUND: Ejection fraction (EF) is an important prognostic factor in heart failure (HF), but administrative claims databases lack information on EF. We previously developed a model to predict EF class from Medicare claims. Here, we evaluated the performance of this model in an external validation sample of commercial insurance enrollees. METHODS: Truven MarketScan claims linked to electronic medical records (EMR) data (IBM Explorys) containing EF measurements were used to identify a cohort of US patients with HF between 01-01-2012 and 10-31-2019. By applying the previously developed model, patients were classified into HF with reduced EF (HFrEF) or preserved EF (HFpEF). EF values recorded in EMR data were used to define gold-standard HFpEF (LVEF ≥45%) and HFrEF (LVEF<45%). Model performance was reported in terms of overall accuracy, positive predicted values (PPV), and sensitivity for HFrEF and HFpEF. RESULTS: A total of 7,001 HF patients with an average age of 71 years were identified, 1,700 (24.3%) of whom had HFrEF. An overall accuracy of 0.81 (95% CI: 0.80-0.82) was seen in this external validation sample. For HFpEF, the model had sensitivity of 0.96 (95%CI, 0.95-0.97) and PPV of 0.81 (95% CI, 0.81-0.82); while for HFrEF, the sensitivity was 0.32 (95%CI, 0.30-0.34) and PPV was 0.73 (95%CI, 0.69-0.76). These results were consistent with what was previously published in US Medicare claims data. CONCLUSIONS: The successful validation of the Medicare claims-based model provides evidence that this model may be used to identify patient subgroups with specific EF class in commercial claims databases as well.

Caregivers of Patients with Heart Failure: Burden and the Determinants of Health-Related Quality of Life.

PURPOSE: To assess the burden among caregivers of patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤60%. The burden by New York Heart Association (NYHA) functional class was also characterized. PATIENTS AND METHODS: A cross-sectional study was conducted in France, Germany, Italy, Spain, and UK from June to November 2019. Patient record forms were completed by 257 cardiologists and 158 general practitioners for consecutive HF patients. Caregivers who accompanied the patient to their consultation completed a caregiver self-completion survey voluntarily, which included the Family Caregiver Quality of Life Questionnaire (FAMQOL) and 5-level 5-dimension EuroQol questionnaire (EQ-5D-5L). RESULTS: We analyzed 361 caregivers of patients with HF (NYHA class I, n=41; II, n=212; III IV, n=108). Mean age of caregivers was 58.8 years (NYHA I/II/III-IV: 59.1/60.8/54.6 years; p=0.0029), with majority being females (73.1%). Caregivers spent on average 19.8 hours/week caring for a HF patient, which increased with increase in NYHA class (I/II/III-IV: 11.8/18.1/25.9 hours/week; p=0.0094). Caregivers (24.1%) reported providing emotional support/encouragement to patients as the most troublesome/inconvenient caregiving activity (no significant difference across NYHA class). Nearly one-third of caregivers experienced stress (NYHA I/II/III-IV: 17.1%/28.8%/40.7%; p=0.0111) and anxiety (26.8%/24.1%/39.8%; p=0.0127) due to caregiving burden. The overall FAMQOL mean score decreased significantly (poorer QoL) with increase in NYHA class (I/II/III-IV: 58.1/56.3/52.2; p=0.0069). A trend of decreasing scores with increasing NYHA class was observed across physical, emotional, and social domains (each p≤0.012). CONCLUSION: Caregivers of HF patients with LVEF ≤60% experienced a significant burden, which was higher among caregivers of patients with more severe and symptomatic disease.

Recurrent heart failure hospitalizations increase the risk of cardiovascular and all-cause mortality in patients with heart failure in Sweden: a real-world study.

AIMS: Heart failure (HF) is a leading cause of hospitalization and is associated with high morbidity and mortality. We examined the impact of recurrent HF hospitalizations (HFHs) on cardiovascular (CV) mortality among patients with HF in Sweden. METHODS AND RESULTS: Adults with incident HF were identified from linked national health registers and electronic medical records from 01 January 2005 to 31 December 2013 for Uppsala and until 31 December 2014 for Västerbotten. CV mortality and all-cause mortality were evaluated. A time-dependent Cox regression model was used to estimate relative CV mortality rates for recurrent HFHs. Assessment was also done for ejection fraction-based HF phenotypes and for comorbid atrial fibrillation, diabetes, or chronic renal impairment. Overall, 3878 patients with HF having an index hospitalization were included, providing 9691.9 patient-years of follow-up. Patients were relatively old (median age: 80 years) and were more frequently male (55.5%). Compared with patients without recurrent HFHs, the adjusted hazard ratio (HR [95% confidence interval; CI]) for CV mortality and all-cause mortality were statistically significant for patients with one, two, three, and four or more recurrent HFHs. The risk of CV mortality and all-cause mortality increased approximately six-fold in patients with four or more recurrent HFHs vs. those without any HFHs (HR [95% CI]: 6.26 [5.24-7.48] and 5.59 [4.70-6.64], respectively). Similar patterns were observed across the HF phenotypes and patients with comorbidities. CONCLUSIONS: There is a strong association between recurrent HFHs and CV and all-cause mortality, with the risk increasing progressively with each recurrent HFH.

Epidemiologic Characterization of Heart Failure with Reduced or Preserved Ejection Fraction Populations Identified Using Medicare Claims.

BACKGROUND: Administrative claims do not contain ejection fraction information for heart failure patients. We recently developed and validated a claims-based model to predict ejection fraction subtype. METHODS: Heart failure patients aged 65 years or above from US Medicare fee-for-service claims were identified using diagnoses recorded after a 6-month baseline period of continuous enrollment, which was used to identify predictors and to apply the claims-based model to distinguish heart failure with reduced or preserved ejection fraction (HFrEF or HFpEF). Patients were followed for the composite outcome of time to first worsening heart failure event (heart failure hospitalization or outpatient intravenous diuretic treatment) or all-cause mortality. RESULTS: A total of 3,134,414 heart failure patients with an average age of 79 years were identified, of which 200,950 (6.4%) were classified as HFrEF. Among those classified as HFrEF, men comprised a larger proportion (68% vs 41%) and the average age was lower (76 vs 79 years) compared with HFpEF. History of myocardial infarction was more common in HFrEF (32% vs 13%), while hypertension was more common in HFpEF (71% vs 77%). One-year cumulative incidence of the composite endpoint was 42.6% for HFrEF and 36.9% for HFpEF. One-year all-cause mortality incidence was similar between the groups (27.4% for HFrEF and 26.4% for HFpEF), however, cardiovascular mortality was higher for HFrEF (15.6% vs 11.3%), whereas noncardiovascular mortality was higher for HFpEF (11.8% vs 15.1%). CONCLUSION: We replicated well-documented differences in key patient characteristics and cause-specific outcomes between HFrEF and HFpEF in populations identified based on the application of a claims-based model.

Incidence of Huntington disease in a northeastern Spanish region: a 13-year retrospective study at tertiary care centre.

BACKGROUND: Despite the progress in the knowledge of Huntington disease (HD) in recent years, the epidemiology continues uncertain, so the study of incidence becomes relevant. This is important since various factors (type of population, diagnostic criteria, disease-modifying factors, etc.) make these data highly variable. Therefore, the genetic diagnosis of these patients is important, since it unequivocally allows the detection of new cases. METHODS: Descriptive retrospective study with 179 individuals. Incidence of HD was calculated from the ratio of number of symptomatic cases newly diagnosed per 100,000 inhabitants per year during the period 2007-2019 in Aragon (Spain). RESULTS: 50 (27.9%) incident cases of HD (CAG repeat length ≥ 36) were identified from a total of 179 persons studied. The remaining 129/179 (72.1%) were HD negative (CAG repeat length < 36). 29 (58.0%) females and 21 (42.0%) males were confirmed as HD cases. The overall incidence was 0.648 per 100,000 patient-years. 11/50 positive HD cases (22.0%) were identified by performing a predictive test, without clinical symptoms. The minimum number of CAG repeats found was 9 and the most common CAG length among HD negative individuals was 16. CONCLUSIONS: Our incidence lied within the range reported for other Caucasian populations. Implementation of new techniques has allowed to determine the exact number of CAG repeats, which is especially important in patients with triplet expansions in an HD intermediate and/or incomplete penetrance allele, both in diagnostic, predictive and prenatal tests.

Recurrent heart failure hospitalizations are associated with increased cardiovascular mortality in patients with heart failure in Clinical Practice Research Datalink.

AIMS: Heart failure (HF) is a leading cause of hospitalization and is associated with high morbidity and mortality post-diagnosis. Here, we examined the impact of recurrent HF hospitalization (HFH) on cardiovascular (CV) and all-cause mortality among HF patients. METHODS AND RESULTS: Adult HF patients identified in the Clinical Practice Research Datalink with a first (index) hospitalization due to HF recorded in the Hospital Episode Statistics data set from January 2010 to December 2014 were included. Patients were followed up until death or end of study (December 2017). CV mortality as primary and as any reported cause and all-cause mortality were evaluated. An extended Cox regression model was used for reporting adjusted relative CV mortality rates for time-dependent recurrent HFHs. Overall, 8603 HF patients with an index hospitalization were included, providing 15 964 patient-years of follow-up. Patients were relatively old (median age: 80 years) and were mostly male (54.6%), with main co-morbidities being hypertension and atrial fibrillation. Recurrent HFHs occurred one, two, three, and more than four times in 1561 (18.2%), 518 (6.02%), 206 (2.4%), and 153 (1.8%) patients, respectively. The median time to mortality was 215 (38-664) days for 50.8% of patients who died for any cause during the study period and 139 (27-531) days for 31.3% who died with CV reasons as primary cause. Compared with those of patients without recurrent HFHs, the adjusted hazard ratios (95% CI) for CV mortality as primary cause were 2.65 (2.35-2.99), 3.69 (3.06-4.43), 5.82 (4.48-7.58), and 5.95 (4.40-8.05) for those with one, two, three, and more than four recurrent HFHs. CONCLUSIONS: There is a strong association between recurrent HFH and CV mortality, with the risk increasing progressively with each recurrent HFH.

A mixed methods approach towards understanding key disease characteristics associated with the progression from RRMS to SPMS: Physicians' and patients' views.

OBJECTIVES: The transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) evolves over time and it can be challenging for physicians to identify progression early. Typically, SPMS is diagnosed retrospectively with a significant delay, based on a history of gradual worsening, independent of relapses, following an initial relapsing-remitting disease course. As such, SPMS is often associated with a considerable period of diagnostic uncertainty. This study aimed to explore and characterize key symptoms and impacts associated with transitioning from RRMS to SPMS and inform the content for a tool to support evaluation of early subtle signs suggestive of progressive disease. METHODS: The qualitative study involved 60-min, face-to-face, concept elicitation (CE) interviews with 32 patients with MS (US = 16 and Germany = 16); and 30-min, telephone, CE interviews with 16 neurologists (US = 8 and Germany = 8). Multivariate analysis on data from a real-world observational study of 3294 MS patients assessed the differences between early-RRMS and early-SPMS, and identified factors that were significant drivers of this difference. These studies informed selection of the key variables to be included in a pilot tool. Sixteen physicians used the pilot tool, presented as a paper questionnaire, with a sample of patients whom they suspected were progressing to SPMS (n ≥ 5). Following this, the physicians participated in a 30-min cognitive debriefing (CD) interview to evaluate the relevance and usefulness of the tool. Qualitative analysis of all anonymized, verbatim transcripts was performed using thematic analysis. RESULTS: Patients and physicians reported signs that indicated progression to SPMS including gradual worsening of symptoms, lack of clear recovery, increased severity and presence of new symptoms. No specific symptoms definitively indicated progression to SPMS, however a number of potential symptoms associated with progression were identified by SPMS patients and physicians, including worsening ambulation, cognition, balance, muscle weakness, visual symptoms, bladder symptoms and fatigue. Quality of life domains reported to be more severely impacted in SPMS than MS in general included: physical activity, work, daily activities, emotional and social functioning. Multivariate analysis of the observational study data identified several variables strongly associated with progression to SPMS including, requirement of assistance in daily living, presence of motor symptoms, presence of ataxia/coordination symptoms, and unemployment. Physicians reported that items included in the tool were easy to understand and relevant. Physicians also reported that there is an unmet need for a tool to help identify signs of SPMS progression and so the tool would be useful in clinical practice. CONCLUSIONS: This was the first stage of development of a novel, validated, physician-completed tool to support physician-patient interactions in evaluating signs indicative of disease progression to SPMS. Qualitative and quantitative methods (involving physician and patients) were used to determine tool content. The usefulness and unmet need for such a tool in clinical practice was confirmed via CD interviews with physicians. Further work is now warranted to develop a scoring algorithm and validate the tool so that it can be reliably implemented in clinical practice.

Identification and mapping of worldwide sources of generic real-world data.

PURPOSE: The demand for real-world data as supportive evidence to traditional clinical studies has increased in the past few years. The present study aimed to identify worldwide generic sources of real-world data and to assess completeness and suitability of selected real-world evidence (RWE) data sources to conduct prespecified research. METHODS: A systematic literature review was conducted to identify generic (non-disease specific) sources of real-world data in Medline and Embase from January 1, 2010 to September 8, 2015. Data sources used in observational studies were identified and summarized based on their geographical distribution and the type of data. In the next step, the selected data sources were critically evaluated for their completeness. RESULTS: A total of 10,069 identified publications were screened, leading to 2635 unique data sources across 102 countries. Europe had the maximum number of data sources (n = 1163) followed by United States (n = 578), and Asia, Middle East, and African Countries (n = 374). The most common type of identified data sources across all countries was structured data sources, ie, administrative databases and registries. Of the identified data sources, 300 were selected for further investigation. From the selected databases, ~50% had confirmed information on over 60% of the investigated variables, ~61% were suitable for epidemiological research, and 60% had possibility of linkage. CONCLUSIONS: The present study applied a systematic literature review approach and identified available generic sources of real-world data worldwide, in addition to the United States and Europe, which are suitable for conducting pre-defined researches and support future RWE studies.

Care pathways and treatment patterns for patients with heart failure in China: results from a cross-sectional survey.

PURPOSE: The objective of this study was to describe the clinical care pathways, management and treatment patterns, and hospitalizations for patients with heart failure (HF) in China. SUBJECTS AND METHODS: A cross-sectional survey of cardiologists and their patients with HF was conducted. Patient record forms were completed by 150 cardiologists for 10 consecutive patients. Patients for whom a patient record form was completed were invited to complete a patient self-completion questionnaire. RESULTS: Most of the 1,500 patients (mean [SD] age 66 [10] years; 55% male) included in the study received care in tier-2 and -3 hospitals in large cities. Cardiologists were responsible for initial consultation, diagnosis, and treatment of patients with HF. The use of guideline-recommended diagnostics was high. However, guideline-recommended double- and triple-combination therapy was received by only 51% and 18% of patients, respectively. In total, 20% of patients with HF reported that they were not consulted on the choice of therapy. Concordance was high (≥80%) between matched cardiologist and patient pairs for the occurrence of side effects, while cardiologists more often under- than overreported the occurrence of side effects of treatment reported by patients. CONCLUSION: The management of HF was predominantly overseen by cardiologists. The use of diagnostic tests was high, but the use of guideline-recommended treatment was low in this population. Improved communication between patients and cardiologists is essential to optimize treatment decision making and to increase awareness of treatment side effects.

Burden of heart failure on patients from China: results from a cross-sectional survey.

PURPOSE: Little evidence exists on the burden that chronic heart failure (HF) poses specifically to patients in China. The objective of this study, therefore, was to describe the burden of HF on patients in China. MATERIALS AND METHODS: A cross-sectional survey of cardiologists and their patients with HF was conducted. Patient record forms were completed by 150 cardiologists for 10 consecutive patients. Patients for whom a patient record form was completed were invited to complete a patient questionnaire. RESULTS: Most of the 933 patients (mean [SD] age 65.8 [10.2] years; 55% male; 80% retired) included in the study received care in tier 2 and 3 hospitals in large cities. Patients gave a median score of 4 on a scale from 1 (no disruption) to 10 (severe disruption) to describe how much HF disrupts their everyday life. Patients in paid employment (8%) missed 10% of work time and experienced 29% impairment in their ability to work due to HF in the previous week. All aspects of patients' health-related quality of life (QoL) were negatively affected by their condition. Mean ± SD utility calculated by the 3-level 5-dimension EuroQol questionnaire was 0.8±0.2, and patients rated their health at 70.3 (11.5) on a 100 mm visual analog scale. Patients incurred costs associated with HF treatment, travel, and professional caregiving services. CONCLUSION: HF is associated with poor health-related QoL and considerable disruption in patients' lives. Novel and improved therapies are needed to reduce the burden of HF on patients and the health care system.

Burden of heart failure on caregivers in China: results from a cross-sectional survey.

PURPOSE: Family and friends play a pivotal role in caring for patients with heart failure (HF); however, evidence of the impact of caregiving is limited. The objectives of this study were to describe the burden of caregiving on informal caregivers of patients with chronic HF in China. MATERIALS AND METHODS: A cross-sectional survey of cardiologists, their patients with HF, and those patients' caregivers was conducted. Patient record forms were completed by 150 cardiologists for 10 consecutive patients. Caregivers of these patients were invited to complete a questionnaire. RESULTS: Overall, 458 caregivers completed a questionnaire (mean ± standard deviation age 60.1±10.6 years; 60% female; 77% spouses; 74% retired). Caregivers spent a mean of 24.5 (16.9) hours caregiving per week, and a third reported a reduction in their social activity, time for themselves, or time for family. Caregivers in employment took several days off work in the past 3 months owing to caregiving, sometimes resulting in reduced income. Up to 79% of caregivers reported an impact on their physical or emotional well-being, and 57% reported deterioration in their objective health status. Inconsistencies stemming from differences in the three-level five-dimension EuroQol questionnaire and HF Caregiver Questionnaire were observed for the impact of caregiving on caregivers' health-related quality of life. CONCLUSION: Assisting patients with HF is associated with caregiver burden. Addressing the needs of caregivers may help to promote their continued support and improve patient outcomes.

Utility of myeloperoxidase in the differential diagnosis of acute coronary syndrome.

OBJECTIVES: To determine the usefulness of myeloperoxidase in discriminating between patients with acute coronary syndrome and patients with chest pain by other causes. METHODS: The study included all patients over 18 years of age who come consecutively to the emergency department from September 2015 to December 2015 with chest pain of non-traumatic origin. The initial patient evaluation was performed according to the study protocol for patients with suspected acute coronary syndrome (ACS) in our Emergency Department. This included the serial measurement of troponin, and in this case myeloperoxidase, with serialization on admission and at 6h. For the determination of myeloperoxidase (MPO), a single step sandwich enzyme immunoassay by Siemens, automated on a Dimension analyser, was used. RESULTS: Statistically significant differences were observed in the concentration of myeloperoxidase at time 0 among patients diagnosed with ACS: 505 (413)pmol/L, and non-ACS patients: 388 (195)pmol/L (p<.001), as well as at 6h (p<.001). An area under the curve ROC of 0.824 was obtained at 6h for ACS patients, with a confidence interval of 95% from 0.715 to 0.933 and a level of significance of p<.001. Statistically significant differences were also found in the concentration of myeloperoxidase at time 0 and at 6h among patients with ACS and patients with heart disease other than coronary artery disease. CONCLUSIONS: The concentration of MPO helps to differentiate between ACS and non-ACS patients, as well as between ACS patients and patients with heart diseases other than coronary artery disease.