Effectiveness and efficiency of a practice accreditation program on cardiovascular risk management in primary care: study protocol of a clustered randomized trial

BACKGROUND: Cardiovascular risk management is largely provided in primary healthcare, but not all patients with established cardiovascular diseases receive preventive treatment as recommended. Accreditation of healthcare organizations has been introduced across the world with a range of aims, including the improvement of clinical processes and outcomes. The Dutch College of General Practitioners has launched a program for accreditation of primary care practices, which focuses on chronic illness care. This study aims to determine the effectiveness and efficiency of a practice accreditation program, focusing on patients with established cardiovascular diseases. METHODS/DESIGN: We have planned a two-arm cluster randomized trial with a block design. Seventy primary care practices will be recruited from those who volunteer to participate in the practice accreditation program. Primary care practices will be the unit of randomization. A computer list of random numbers will be generated by an independent statistician. The intervention group (n = 35 practices) will be instructed to focus improvement on cardiovascular risk management. The control group will be instructed to focus improvement on other domains in the first year of the program. Baseline and follow-up measurements at 12 months after receiving the accreditation certificate are based on a standardized version of the audit in the practice accreditation program. Primary outcomes include controlled blood pressure, serum cholesterol, and prescription of recommended preventive medication. Secondary outcomes are 15 process indicators and two outcome indicators of cardiovascular risk management, self-reported achievement of improvement goals and perceived unintended consequences. The intention to treat analysis is statistically powered to detect a difference of 10% on primary outcomes. The economic evaluation aims to determine the efficiency of the program and investigates the relationship between costs, performance indicators, and accreditation. DISCUSSION: It is important to gain more information about the effectiveness and efficiency of the practice accreditation program to assess if participation is worthwhile regarding the quality of cardiovascular risk management. The results of this study will help to develop the practice accreditation program for primary care practices. TRIAL REGISTRATION: This cluster randomized trial is registered at ClinicalTrials.gov nr NCT0079136

Is guideline-adherent prescribing associated with quality of life in patients with type 2 diabetes?

BACKGROUND: Guideline-adherent prescribing for treatment of multiple risk factors in type 2 diabetes (T2D) patients is expected to improve clinical outcomes. However, the relationship to Health-Related Quality of Life (HRQoL) is not straightforward since guideline-adherent prescribing can increase medication burden.OBJECTIVES: To test whether guideline-adherent prescribing and disease-specific medication burden are associated with HRQoL in patients with T2D.METHODS: Cross-sectional study including 1,044 T2D patients from the e-VitaDM/ZODIAC study in 2012 in the Netherlands. Data from the diabetes visit, such as laboratory and physical examinations and prescribed medication, and from two HRQoL questionnaires, the EuroQol 5 Dimensions 3 Levels (EQ5D-3L) and the World Health Organization Well-Being Index (WHO-5) were collected. Twenty indicators assessing prescribing of recommended glucose lowering drugs, statins, antihypertensives and renin-angiotensin-aldosterone system (RAAS)-inhibitors and potentially inappropriate drugs from a validated diabetes indicator set were included. Disease-specific medication burden was assessed using a modified version of the Medication Regimen Complexity Index (MRCI). Associations were tested with regression models, adjusting for age, gender, diabetes duration, comorbidity, body mass index and smoking.RESULTS: The mean MRCI was 7.1, the median EQ5D-3L-score was 0.86 and the mean WHO-5 score was 72. Seven indicators included too few patients and were excluded from the analysis. The remaining thirteen indicators focusing on recommended start, intensification, current and preferred use of glucose lowering drugs, statins, antihypertensives, RAAS inhibitors, and on inappropriate prescribing of glibenclamide and dual RAAS blockade were not significantly associated with HRQoL. Finally, also the MRCI was not associated with HRQoL.CONCLUSIONS: We found no evidence for associations between guideline-adherent prescribing or disease-specific medication burden and HRQoL in T2D patients. This gives no rise to refrain from prescribing intensive treatment in T2D patients as recommended, but the interpretation of these results is limited by the cross-sectional study design and the selection of patients included in some indicators.</p

Safe use of proton pump inhibitors in patients with cirrhosis

Aims: Proton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in patients with cirrhosis. Methods: A systematic literature search identified studies on the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown. Guidance was aimed at the oral use of PPIs and categorized by the severity of cirrhosis, using the Child–Turcotte–Pugh (CTP) classification. Results: A total of 69 studies were included. Esomeprazole, omeprazole and rabeprazole were classified as having ‘no additional risks known’. A reduction in maximum dose of omeprazole and rabeprazole is recommended for CTP A and B patients. For patients with CTP C cirrhosis, the only PPI advised is esomeprazole at a maximum dosage of 20 mg per day. Pantoprazole and lansoprazole were classified as unsafe because of 4- to 8-fold increased exposure. The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy and should be carefully considered. Conclusions: We suggest using esomeprazole, omeprazole or rabeprazole in patients with CTP A or B cirrhosis and only esomeprazole in patients with CTP C. Pharmacokinetic changes are also important to consider when prescribing PPIs to vulnerable, cirrhotic patients

Evaluating the safety and dosing of drugs in patients with liver cirrhosis by literature review and expert opinion

INTRODUCTION: Liver cirrhosis can have a major impact on drug pharmacokinetics and pharmacodynamics. Patients with cirrhosis often suffer from potentially preventable adverse drug reactions. Guidelines on safe prescribing for these patients are lacking. The aim of this study is to develop a systematic method for evaluating the safety and optimal dosage of drugs in patients with liver cirrhosis. METHODS AND ANALYSIS: For each drug, a six-step evaluation process will be followed. (1) Available evidence on the pharmacokinetics and safety of a drug in patients with liver cirrhosis will be collected from the Summary of Product Characteristics (SmPC) and a systematic literature review will be performed. (2) Data regarding two outcomes, namely pharmacokinetics and safety, will be extracted and presented in a standardised assessment report. (3) A safety classification and dosage suggestion will be proposed for each drug. (4) An expert panel will discuss the validity and clinical relevance of this suggested advice. (5) Advices will be implemented in all relevant Clinical Decision Support Systems in the Netherlands and published on a website for patients and healthcare professionals. (6) The continuity of the advices will be guaranteed by a yearly check of new literature and comments on the advices. This protocol will be applied in the evaluation of a selection of drugs: (A) drugs used to treat (complications of) liver cirrhosis, and (B) drugs frequently prescribed to the general population. ETHICS AND DISSEMINATION: Since this study does not directly involve human participants, it does not require ethical clearance. Besides implementation on a website and in clinical decision support systems, we aim to publish the generated advices of one or two drug classes in a peer-reviewed journal and at conference meetings

Safe use of proton pump inhibitors in patients with cirrhosis

AimsProton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in patients with cirrhosis. MethodsA systematic literature search identified studies on the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown. Guidance was aimed at the oral use of PPIs and categorized by the severity of cirrhosis, using the Child-Turcotte-Pugh (CTP) classification. ResultsA total of 69 studies were included. Esomeprazole, omeprazole and rabeprazole were classified as having no additional risks known'. A reduction in maximum dose of omeprazole and rabeprazole is recommended for CTP A and B patients. For patients with CTP C cirrhosis, the only PPI advised is esomeprazole at a maximum dosage of 20mg per day. Pantoprazole and lansoprazole were classified as unsafe because of 4- to 8-fold increased exposure. The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy and should be carefully considered. ConclusionsWe suggest using esomeprazole, omeprazole or rabeprazole in patients with CTP A or B cirrhosis and only esomeprazole in patients with CTP C. Pharmacokinetic changes are also important to consider when prescribing PPIs to vulnerable, cirrhotic patients

Characterisation of the MHC region in the Australian black flying fox, Pteropus alecto

Bats are widely recognised as natural reservoirs to numerous highly pathogenic zoonotic viruses. Their ability to remain clinically asymptomatic during most viral infection has presented a great challenge and opportunity to the very young field of bat immunology. The major histocompatibility complex (MHC) plays a central role in the innate and adaptive immune responses. This dissertation characterises the MHC region and MHC genes of the black flying fox (Pteropus alecto), providing the first insights into the MHC region of any species of bat. A partial MHC class I (MHC-I) region, a complete class II and complete class III region were identified from the current bat genome sequence assembly. All three bat MHC regions were highly contracted with conserved and syntenic gene content when compared to other mammals. Overall, the bat MHC resembles the ancestral architecture of the immune supercomplex. However, no MHC-I genes were identified in the bat genome. Sequencing of bacterial artificial chromosome (BAC) and cDNA clones resulted in the identification of 16 MHC-I loci, eight of which have preliminarily been classified as putative classical class I genes, more than any other species. Furthermore, a subset of the MHC-I genes contains a bat-specific five amino acid insertion within the α1 domain of the peptide-binding groove (PBG), potentially accommodating a larger and more diverse repertoire of antigens. A greater number of classical class I genes, together with the presence of a unique PBG, could potentially be one of the keys in the ability of bats to more effectively control viral infection. Twelve MHC class II genes, with orthology to class II genes from other mammals, were also identified in the bat genome. To our knowledge, this is also the first successful attempt at employing next generation sequencing technologies to resolve the highly complex and repetitive MHC region