Hospitalization Rates in Patients with Heart Failure and Reduced Ejection Fraction Initiating Sacubitril/Valsartan or Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers: A Retrospective Cohort Study.

Introduction: The angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan (SAC/VAL) has shown benefit in patients with symptomatic heart failure (HF), including those naïve to renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, and is considered the preferred RAASi for chronic HF. Real-world data on ARNI, specifically in RAASi-naïve patients, are limited. This study compared real-world outcomes of ARNI (SAC/VAL) vs.

Physician adjudication of angioedema diagnosis codes in a population of patients with heart failure prescribed angiotensin-converting enzyme inhibitor therapy.

Purpose: Our objective was to calculate the positive predictive value (PPV) of the ICD-9 diagnosis code for angioedema when physicians adjudicate the events by electronic health record review. Our secondary objective was to evaluate the inter-rater reliability of physician adjudication.

Methods: Patients from the Cardiovascular Research Network previously diagnosed with heart failure who were started on angiotensin-converting enzyme inhibitors (ACEI) during the study period (July 1, 2006 through September 30, 2015) were included.

Heart failure signs and symptoms, hospital referrals, and prescription patterns in patients receiving sacubitril/valsartan in primary care and cardiologist settings in Germany.

Aims: The aim of this paper was to analyse heart failure (HF) signs and symptoms, hospital referrals, and prescription patterns in patients receiving sacubitril/valsartan (sac/val) in primary care and cardiology settings in Germany.

Methods And Results: A retrospective cohort study of electronic medical records identified 1263 adults (aged ≥18 years) in the German IMS® Disease Analyzer database who were prescribed sac/val during 2016 and had at least 6 months of data following sac/val initiation. Clinical characteristics were collected during the 12 months before the first recorded sac/val prescription (index date) and 6 months post-index.

Risk reduction of diarrhea and respiratory infections following a community health education program - a facility-based case-control study in rural parts of Kenya.

Background: Diarrheal and acute respiratory infections remain a major cause of death in developing countries especially among children below 5 years of age. About 80% of all hospital attendances in Kenya can be attributed to preventable diseases and at least 50% of these preventable diseases are linked to poor sanitation. The purpose of this study was to assess the impact of a community-based health education program, called Familia Nawiri, in reducing the risk of diarrhea and respiratory infections among people living in three rural Kenyan communities.

Association between vildagliptin and risk of angioedema, foot ulcers, skin lesions, hepatic toxicity, and serious infections in patients with type 2 diabetes mellitus: A European multidatabase, noninterventional, postauthorization safety study.

Objectives: This noninterventional, multidatabase, analytical cohort study explored whether vildagliptin is associated with an increased risk of specific safety events of interest, namely angioedema, foot ulcers, or skin lesions, adverse hepatic events, or serious infections compared with other noninsulin antidiabetic drugs (NIADs) using real-world data from five European electronic healthcare databases.

Design: Patients with type 2 diabetes mellitus aged ≥18 years on NIAD treatment were included between January 2005 and June 2014. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the outcomes of interest were estimated using negative binomial regression.

Care-Seeking Dynamics among Patients with Diabetes Mellitus and Hypertension in Selected Rural Settings in Kenya.

Diabetes mellitus and hypertension are two common non-communicable diseases (NCDs) that often coexist in patients. However, health-seeking behaviour in patients with diabetes mellitus or hypertension has not been extensively studied especially in low- and middle-income countries. This study aimed to examine care-seeking dynamics among participants diagnosed with diabetes and/or hypertension across nine counties in rural Kenya.

Pancreatic safety of vildagliptin in patients with type 2 diabetes mellitus: A European, noninterventional, postauthorization safety study.

This cohort study assessed the pancreatic safety of vildagliptin versus other noninsulin antidiabetic drugs (NIADs) based on data from five European electronic health care databases. Patients with type 2 diabetes aged ≥18 years on NIAD treatment were enrolled. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated separately for acute pancreatitis and pancreatic cancer for vildagliptin (± other NIADs) compared with other NIADs using negative binomial regression.

Real-world treatment patterns of sacubitril/valsartan: a longitudinal cohort study in Germany.

Aims: To analyse real-world treatment patterns of sacubitril/valsartan (sac/val) using data from a pharmacy database in Germany.

Methods And Results: A retrospective cohort study of 26 191 adult patients (aged ≥ 18 years) in the IMS® longitudinal prescriptions database in Germany who were dispensed sac/val from January 2016 to June 2017 was conducted. The analysis included sac/val dose titration assessed in the 6 months from first sac/val prescription; prescriptions of concomitant cardiovascular medications in the 6 months pre- and post-index and compliance and persistence during 12 months post-index.

Epidemiology of heart failure and trends in diagnostic work-up: a retrospective, population-based cohort study in Sweden.

Purpose: The purpose of this study was to examine the trends in heart failure (HF) epidemiology and diagnostic work-up in Sweden.

Methods: Adults with incident HF (≥2 ICD-10 diagnostic codes) were identified from linked national health registers (cohort 1, 2005-2013) and electronic medical records (cohort 2, 2010-2015; primary/secondary care patients from Uppsala and Västerbotten). Trends in annual HF incidence rate and prevalence, risk of all-cause and cardiovascular disease (CVD)-related 1-year mortality and use of diagnostic tests 6 months before and after first HF diagnosis (cohort 2) were assessed.

Characteristics of early sacubitril/valsartan patients and considerations for studies in electronic health record data.

Aim: We examined characteristics of early sacubitril/valsartan users in a large US electronic health records database.

Patients & Methods: We identified three cohorts of patients with heart failure (HF): sacubitril/valsartan patients with a prior HF diagnosis; patients with HF with reduced ejection fraction; and patients with HF treated with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and a β-blocker.

Results: Sacubitril/valsartan patients were younger than patients in the other cohorts; the mean age of sacubitril/valsartan patients increased by 2 years in the first 15 months of marketing.

Early insights into the characteristics and evolution of clinical parameters in a cohort of patients prescribed sacubitril/valsartan in Germany.

Objectives: This study aimed to provide early insights into sacubitril/valsartan (sac/val) prescription patterns and the demographic and clinical characteristics of patients prescribed sac/val in primary care and cardiology settings in Germany.

Methods: The study used electronic medical records from the German IMS® Disease Analyzer database. Patients with ≥1 prescription for sac/val during 1 January-31 December 2016 (n = 1643) were identified and followed up for ≤12 months from first prescription.

A Database Cohort Study to Assess the Risk of Angioedema Among Patients with Heart Failure Initiating Angiotensin-Converting Enzyme Inhibitors in the USA.

Introduction: Real-world evidence on the risk of angioedema associated with angiotensin-converting enzyme inhibitors (ACEIs) in patients with heart failure (HF) is scarce.

Objective: This non-interventional study aimed to estimate the incidence of and risk factors for angioedema in patients with HF initiating an ACEI in real-world practice.

Methods: This was a retrospective cohort study using claims data from the PharMetrics Plus database, supplemented with consumer health data, from 1 January 2007 to 31 March 2015.

Angioedema Among Hypertensive Patients Treated with Aliskiren or Other Antihypertensive Medications in the United States.

Background: A non-interventional study suggested that use of angiotensin-converting enzyme inhibitors (ACEIs) or aliskiren was associated with an angioedema risk three times that of beta-blockers (BBs).

Objective: The aim was to assess angioedema incidence rates (IRs) and the relative angioedema risk of aliskiren compared to other antihypertensive drugs (AHDs).

Methods: A cohort study in hypertensive patients with an AHD prescription between 2007 and 2012 was conducted using data from the US PharMetrics Plus™ claims database.

Cardiovascular safety of vildagliptin in patients with type 2 diabetes: A European multi-database, non-interventional post-authorization safety study.

The aim of this non-interventional, multi-database, analytical cohort study was to assess the cardiovascular (CV) safety of vildagliptin vs other non-insulin antidiabetic drugs (NIADs) using real-world data from 5 European electronic healthcare databases. Patients with type 2 diabetes aged ≥18 years on NIAD treatment were enrolled. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the outcomes of interest (myocardial infarction [MI], acute coronary syndrome [ACS], stroke, congestive heart failure [CHF], individually and as a composite) were estimated using negative binomial regression.

Multi-centre, multi-database studies with common protocols: lessons learnt from the IMI PROTECT project.

Purpose: To assess the impact of a variety of methodological parameters on the association between six drug classes and five key adverse events in multiple databases.

Methods: The selection of Drug-Adverse Event pairs was based on public health impact, regulatory relevance, and the possibility to study a broad range of methodological issues. Common protocols and data analytical specifications were jointly developed and independently and blindly executed in different databases in Europe with replications in the same and different databases.

Case-only designs for studying the association of antidepressants and hip or femur fracture.

Purpose: The purpose of this study is to evaluate the performance and validity of the case-crossover (CCO) and self-controlled case-series (SCCS) designs when studying the association between hip/femur fracture (HF) and antidepressant (AD) use in general practitioner databases. In addition, comparability with cohort and case-control designs is discussed.

Methods: Adult patients with HF and who received an AD prescription during 2001-2009 were identified from UK's The Health Improvement Network (THIN) and the Dutch Mondriaan databases.

Understanding inconsistency in the results from observational pharmacoepidemiological studies: the case of antidepressant use and risk of hip/femur fractures.

Purpose: Results from observational studies on the same exposure-outcome association may be inconsistent because of variations in methodological factors, clinical factors or health care systems. We evaluated the consistency of results assessing the association between antidepressant use and the risk of hip/femur fractures in three European primary care databases using two different study designs.

Methods: Cohort and nested case control studies were conducted in three European primary care databases (Spanish BIFAP, Dutch Mondriaan and UK THIN) to assess the association between use of antidepressants and hip/femur fracture.

Risk of acute liver injury associated with use of antibiotics. Comparative cohort and nested case-control studies using two primary care databases in Europe.

Purpose: To assess the impact of varying study designs, exposure and outcome definitions on the risk of acute liver injury (ALI) associated with antibiotic use.

Methods: The source population comprised of patients registered in two primary care databases, in the UK and in Spain. We identified a cohort consisting of new users of antibiotics during the study period (2004-2009) and non-users during the study period or in the previous year.

The IMI PROTECT project: purpose, organizational structure, and procedures.

The Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT) initiative was a collaborative European project that sought to address limitations of current methods in the field of pharmacoepidemiology and pharmacovigilance. Initiated in 2009 and ending in 2015, PROTECT was part of the Innovative Medicines Initiative, a joint undertaking by the European Union and pharmaceutical industry. Thirty-five partners including academics, regulators, small and medium enterprises, and European Federation of Pharmaceuticals Industries and Associations companies contributed to PROTECT.

Prevalence of antibiotic use: a comparison across various European health care data sources.

Purpose: There is widespread concern about increases in antibiotic use, but comparative data from different European countries on rates of use are lacking. This study was designed to measure and understand the variation in antibiotic utilization across five European countries.

Methods: Seven European healthcare databases with access to primary care data from Denmark, Germany, the Netherlands, Spain and the UK were used to measure and compare the point and 1-year-period prevalence of antibiotic use between 2004 and 2009.

Exposure to benzodiazepines (anxiolytics, hypnotics and related drugs) in seven European electronic healthcare databases: a cross-national descriptive study from the PROTECT-EU Project.

Purpose: Studies on drug utilization usually do not allow direct cross-national comparisons because of differences in the respective applied methods. This study aimed to compare time trends in BZDs prescribing by applying a common protocol and analyses plan in seven European electronic healthcare databases.

Methods: Crude and standardized prevalence rates of drug prescribing from 2001-2009 were calculated in databases from Spain, United Kingdon (UK), The Netherlands, Germany and Denmark.

Do case-only designs yield consistent results across design and different databases? A case study of hip fractures and benzodiazepines.

Background: The case-crossover (CXO) and self-controlled case series (SCCS) designs are increasingly used in pharmacoepidemiology. In both, relative risk estimates are obtained within persons, implicitly controlling for time-fixed confounding variables.

Objectives: To examine the consistency of relative risk estimates of hip/femur fractures (HFF) associated with the use of benzodiazepines (BZD) across case-only designs in two databases (DBs), when a common protocol was applied.

Hip/femur fractures associated with the use of benzodiazepines (anxiolytics, hypnotics and related drugs): a methodological approach to assess consistencies across databases from the PROTECT-EU project.

Background: Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed.

Objectives: The objectives of this paper were to evaluate the impact of applying a common study protocol to study benzodiazepines (BZDs) (anxiolytics, hypnotics, and related drugs) and the risk of hip/femur fracture (HFF) across three European primary care DBs and to investigate any resulting discrepancies.

Methods: To measure the risk of HFF among adult users of BZDs during 2001-2009, three cohort and nested case control (NCC) studies were performed in Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) (Spain), Clinical Practice Research Datalink (CPRD) (UK), and Mondriaan (The Netherlands).

Time trends of period prevalence rates of patients with inhaled long-acting beta-2-agonists-containing prescriptions: a European comparative database study.

Background: Inhaled, long-acting beta-2-adrenoceptor agonists (LABA) have well-established roles in asthma and/or COPD treatment. Drug utilisation patterns for LABA have been described, but few studies have directly compared LABA use in different countries. We aimed to compare the prevalence of LABA-containing prescriptions in five European countries using a standardised methodology.