EU-Wide Cross-Sectional Observational Study of Lipid-Modifying Therapy Use in Secondary and Primary Care: the DA VINCI study.

AIMS: To provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low-density lipoprotein cholesterol (LDL-C) goal achievement. METHODS AND RESULTS: An 18 country, cross-sectional, observational study of patients prescribed LLT for primary or secondary prevention in primary or secondary care across Europe. Between June 2017 and November 2018, data were collected at a single visit, including LLT in the preceding 12 months and most recent LDL-C. Primary outcome was the achievement of risk-based 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) LDL-C goal while receiving stabilized LLT; 2019 goal achievement was also assessed. Overall, 5888 patients (3000 primary and 2888 secondary prevention patients) were enrolled; 54% [95% confidence interval (CI) 52-56] achieved their risk-based 2016 goal and 33% (95% CI 32-35) achieved their risk-based 2019 goal. High-intensity statin monotherapy was used in 20% and 38% of very high-risk primary and secondary prevention patients, respectively. Corresponding 2016 goal attainment was 22% and 45% (17% and 22% for 2019 goals) for very high-risk primary and secondary prevention patients, respectively. Use of moderate-high-intensity statins in combination with ezetimibe (9%), or any LLT with PCSK9 inhibitors (1%), was low; corresponding 2016 and 2019 goal attainment was 53% and 20% (ezetimibe combination), and 67% and 58% (PCSK9i combination). CONCLUSION: Gaps between clinical guidelines and clinical practice for lipid management across Europe persist, which will be exacerbated by the 2019 guidelines. Even with optimized statins, greater utilization of non-statin LLT is likely needed to reduce these gaps for patients at highest risk.

Validation and validity of diagnoses in the General Practice Research Database: a systematic review.

AIMS: To investigate the range of methods used to validate diagnoses in the General Practice Research Database (GPRD), to summarize findings and to assess the quality of these validations. METHODS: A systematic literature review was performed by searching PubMed and Embase for publications using GPRD data published between 1987 and April 2008. Additional publications were identified from conference proceedings, back issues of relevant journals, bibliographies of retrieved publications and relevant websites. Publications that reported attempts to validate disease diagnoses recorded in the GPRD were included. RESULTS: We identified 212 publications, often validating more than one diagnosis. In total, 357 validations investigating 183 different diagnoses met our inclusion criteria. Of these, 303 (85%) utilized data from outside the GPRD to validate diagnoses. The remainder utilized only data recorded in the database. The median proportion of cases with a confirmed diagnosis was 89% (range 24-100%). Details of validation methods and results were often incomplete. CONCLUSIONS: A number of methods have been used to assess validity. Overall, estimates of validity were high. However, the quality of reporting of the validations was often inadequate to permit a clear interpretation. Not all methods provided a quantitative estimate of validity and most methods considered only the positive predictive value of a set of diagnostic codes in a highly selected group of cases. We make recommendations for methodology and reporting to strengthen further the use of the GPRD in research.

Do selected drugs increase the risk of lupus? A matched case-control study.

AIM: To investigate the association between risk of lupus and exposure to selected drugs implicated in risk of lupus in a number of case reports. METHODS: In this matched nested case-control study we utilized primary care data from the UK General Practice Research Database recorded between 1987 and 2001. Cases with at least one medical code for systemic lupus erythematosus or drug-induced lupus in their computerized records were matched to controls without a medical code for lupus or any other autoimmune disorder. Using conditional logistic regression we computed odds ratios (OR) and 95% confidence intervals (CI) for risk of lupus associated with exposure to selected drugs. RESULTS: There were 875 incident cases, of which 12% (n= 107) had evidence of a prescription for one or more of the suspected drugs, and 3632 matched controls. For some drugs, prescriptions were too uncommon to be able to estimate associated risk of lupus. Despite small numbers of exposed patients and low statistical precision we observed an increased risk of lupus for hydralazine (OR = 6.62, 95% CI 1.03, 42.74), minocycline (OR = 4.23, 95% CI 2.65, 6.75) and carbamazepine (OR = 1.88, 95% CI 1.09, 3.22). There was some indication that the effect of carbamazepine was restricted to women (P for interaction by gender = 0.047). CONCLUSION: This study shows that even those drugs suggested by case reports as causing lupus cannot all be clearly shown to be associated, even in a very large population-based database. Our findings support causal relationships for carbamazepine, minocycline and possibly hydralazine. Overall, drugs do not seem to be a major cause of lupus.

Risk for hospital contact with infection in patients with splenectomy: a population-based cohort study.

BACKGROUND: Splenectomy has been associated with increased risk for infection. OBJECTIVE: To assess the magnitude and duration of risk for hospital contact with infection associated with splenectomy. DESIGN: Population-based cohort study. SETTING: Denmark. PATIENTS: All 3812 persons in Denmark who underwent splenectomy from 1996 to 2005. Splenectomized patients were matched to 3 comparison cohorts: the general population, appendectomized patients, and unsplenectomized patients with indications for splenectomy. MEASUREMENTS: Relative risks were assessed for hospital contact involving any infection, pneumonia, and microbiologically confirmed bacteremia among 3812 splenectomized patients and their matched comparisons, during different follow-up periods and after regression analysis for confounder adjustment. RESULTS: The adjusted relative risk for any hospital contact with infection was highest within 90 days of splenectomy: 10.2% vs. 0.6% among general population comparisons (adjusted odds ratio, 18.1 [95% CI, 14.8 to 22.1]) and 10.2% vs. 4.2% among appendectomized patients (adjusted odds ratio, 2.4 [CI, 2.1 to 2.8]). The hazard of infection was 4.6-fold (CI, 3.8 to 5.5) higher in splenectomized patients than in general population comparisons from 91 to 365 days after splenectomy and 2.5 times (CI, 2.2 to 2.8) higher more than 365 days after splenectomy. The risks were similar for pneumonia and were higher for bacteremia. Markedly increased risks were also found when compared with those of appendectomized patients. Modest increases in infection risk were seen with splenectomy matched-indication comparisons (adjusted 90-day odds ratio, 1.7 [CI, 1.5 to 2.1]; hazard ratios, 1.5 [CI, 1.2 to 1.8] from 91 to 365 days after splenectomy and 1.2 [CI, 1.1 to 1.4] beyond 365 days after splenectomy). Relative risks for infection were highest in patients who had splenectomy because of hematologic disorders. LIMITATION: Increased surveillance among splenectomized patients may have affected the findings. CONCLUSION: Splenectomy is associated with increased long-term risk for infections involving hospital contact.

Epidemiology of immune thrombocytopenic purpura in the General Practice Research Database.

The epidemiology of immune thrombocytopenic purpura (ITP) is not well-characterised in the general population. This study described the incidence and survival of ITP using the UK population-based General Practice Research Database (GPRD). ITP patients first diagnosed in 1990-2005 were identified in the GPRD. Overall incidence rates (per 100,000 person-years) and rates by age, sex, and calendar periods were calculated. Survival analysis was conducted using the Kaplan-Meier and proportional hazard methods. A total of 1145 incident ITP patients were identified. The crude incidence was 3.9 (95% confidence interval [CI]: 3.7-4.1). Overall average incidence was statistically significantly higher in women (4.4, 95% CI: 4.1-4.7) compared to men (3.4; 95% CI: 3.1-3.7). Among men, incidence was bimodal with peaks among ages under 18 and between 75-84 years. The hazard ratio for death among ITP patients was 1.6 (95% CI: 1.3-1.9) compared to age- and sex-matched comparisons. During follow-up 139 cases died, of whom 75 had a computerised plausible cause of death. Death was related to bleeding in 13% and infection in 19% of these 75. In conclusion, ITP incidence varies with age and is higher in women than men. This potentially serious medical condition is associated with increased mortality in the UK.

Thromboembolism in patients with immune thrombocytopenia (ITP): a meta-analysis of observational studies.

This meta-analysis describes the incidence rate of arterial and venous thromboembolism (ATE and VTE) in patients with immune thrombocytopenia (ITP), and the relative risk of ATE and VTE in patients with ITP and comparable populations without ITP. MEDLINE and EMBASE were systematically searched for observational studies reporting incidence rates of ATE and VTE in populations with and without ITP between 1996 and 2013 [follow-up completed before thrombopoietin receptor (TPOr) agonists were commercially available]. Three large, population-based studies were identified from Denmark, the United Kingdom, and the United States. The incidence of ATE per 100 patient-years among patients with ITP ranged from 1.0 to 2.8, and among populations without ITP ranged from 0.7 to 1.8; the summary relative risk adjusted for matching factors (aRR) was 1.5 [95 % confidence interval (CI) 1.3, 1.8]. The incidence of VTE per 100 patient-years among patients with ITP ranged from 0.4 to 0.7, and among populations without ITP ranged from 0.1 to 0.4; the summary aRR (95 % CI) was 1.9 (1.4, 2.7). The risk of ATE and VTE among patients with ITP, based on evidence from three large, population-based observational studies, should be considered when evaluating the risk of thromboembolism attributed to ITP treatments, such as TPOr agonists.

Mortality risk in splenectomised patients: a Danish population-based cohort study.

BACKGROUND: The extent and magnitude of mortality risk among patients splenectomised for a variety of indications is not well-described in the literature. We assessed mortality risk among splenectomised patients compared to the general population and to un-splenectomised patients with similar underlying medical conditions. METHODS: We conducted a historical population-based cohort study in Denmark between January 1, 1996 and December 31, 2005. Mortality risk was evaluated within 90 days, 91-365 days, and >365 days post-splenectomy, controlling for age, sex, and comorbid conditions using Cox proportional hazards models for a splenectomised cohort compared to the general Danish population and a matched indication cohort. RESULTS: We identified a total of 3812 splenectomised patients, 38,120 population comparisons, and 8310 matched indication comparisons. Within 90 days post-splenectomy, the adjusted relative risk (RR) for death, regardless of indication, was highly elevated compared to the general population: RR 33.6 [95% confidence interval (CI): 6.9, 35.0]. This risk declined substantially after 90 days post-splenectomy but remained higher 365 days post-splenectomy for all indications compared to the general population. When compared to the matched indication cohort, short- and long-term mortality risk with splenectomy was not increased. CONCLUSION: Regardless of indication, the adjusted short- and long-term risk of death for splenectomised patients was higher than the general population. Most of this risk seems to be due to the underlying splenectomy indication and not to splenectomy alone.

Characteristics of US patients with myelodysplastic syndromes: results of six cross-sectional physician surveys.

BACKGROUND: Myelodysplastic syndromes (MDS) comprise a group of pathologically and cytogenetically distinct bone marrow disorders. Little is known about the characteristics of MDS patients, including their pathological and prognostic classifications, cytopenias, transfusion and supportive care needs, and treatment regimens. We describe these characteristics in a large group of recently diagnosed and existing (ie, established) MDS patients. METHODS: We conducted six consecutive cross-sectional surveys among US hematology and medical oncology specialists (identified from an American Medical Association [AMA] database of physicians who administer chemotherapy) between June 2005 and January 2007. A questionnaire collected data on the characteristics and treatment patterns of the 4-10 most recently seen MDS patients for each physician, including demographic data, transfusion needs, treatment approaches, and consideration for clinical trials or bone marrow transplantation. RESULTS: A panel of 101 physicians who were geographically representative of physicians registered with the AMA characterized 614-827 patients per survey, for a total of 4514 responses. Among recently diagnosed patients, 55% were male (95% confidence interval [CI] = 52% to 59%), the median age at diagnosis was 71 years (range = 65-80 years), and 10% (95% CI = 8% to 12%) had MDS secondary to chemotherapy, radiation therapy, or environmental exposure. The median duration of MDS in established patients ranged from 13 to 16 months over the six surveys. Among recently diagnosed MDS patients, fewer patients with lower-risk disease than with higher-risk disease were dependent on either red blood cell transfusions (22% vs 68%) or platelet transfusions (6% vs 33%). More than 50% of all newly diagnosed and established patients used erythropoiesis-stimulating agents. A small percentage of all patients either had had or were being considered for bone marrow transplantation (recently diagnosed: 4%; established: 4% or less) or were being treated on clinical trials (recently diagnosed: 1%; established: 4% or less). CONCLUSIONS: MDS patients in the United States have substantial transfusion needs, and use of erythropoiesis-stimulating agents and are seldom considered for bone marrow transplantation or clinical trials. These data may be useful in characterizing the health care resource use and pharmacoeconomic impact of MDS in the United States.

Incidence of systemic lupus erythematosus in the United Kingdom, 1990-1999.

OBJECTIVE: To estimate the annual incidence of systemic lupus erythematosus (SLE) over a 10-year period in the UK, and to examine age-, sex-, and region-specific rates. METHODS: The study was based on the UK General Practice Research Database (GPRD), which covers approximately 5% of the UK population. We estimated SLE incidence rates, during the period 1990-1999, among persons registered with practices contributing to the GPRD, representing >33 million person-years of observation. RESULTS: A total of 1,638 patients with incident SLE (1,374 females, 264 males) were identified. The age-standardized SLE incidence in the UK during the 1990s was 7.89 per 100,000 (95% confidence interval [95% CI] 7.46, 8.31) for females and 1.53 per 100,000 (95% CI 1.34, 1.71) for males (overall female-to-male ratio 5.2:1). Peak incidence occurred at age 50-54 years for females and 70-74 years for males. There was a small but insignificant increase of SLE incidence over the 10 years among females but not males. No clear association between latitude and SLE incidence was found, but regional variations existed, with age-standardized rates ranging from 3.56 per 100,000 (95% CI 3.00, 4.13) for the West Midlands to 7.62 per 100,000 (95% CI 5.59, 9.65) for Northern Ireland. CONCLUSION: This study provides updated estimates of SLE incidence in the UK. Standard methodology throughout the study period and target population allowed for comparison of rates over time and across regions.

Alcohol consumption and risk of prostate cancer in middle-aged men.

Alcohol consumption is a modifiable lifestyle factor that may affect prostate cancer risk. Alcohol alters the hormonal milieu and contains chemical substances such as flavonoids (red wine), which may alter tumor cell growth. Data from a population-based case-control study in King County, WA, were utilized to evaluate the association of alcohol consumption with prostate cancer in middle-aged men. A total of 753 newly diagnosed prostate cancer cases, 40-64 years of age, participated in the study. Seven hundred three control subjects, frequency matched to cases by age, were selected through random digit dialing. All participants completed an in-person interview on lifetime alcohol consumption and other risk factors for prostate cancer. Logistic regression models were used to estimate odds ratios (OR) and assess significance (95% confidence intervals [CI]). All tests of statistical significance were two-sided. No clear association with prostate cancer risk was seen for overall alcohol consumption. Each additional glass of red wine consumed per week showed a statistically significant 6% decrease in relative risk (OR = 0.94; 95% CI = 0.90-0.98), and there was evidence for a decline in risk estimates across increasing categories of red wine intake (trend p = 0.02). No clear associations were seen for consumption of beer or liquor. Our present study suggests that consumption of beer or liquor is not associated with prostate cancer. There may be, however, a reduced relative risk associated with increasing level of red wine consumption. Further research is needed to evaluate the potential negative association between red wine intake and prostate cancer risk.