Utilisation of disease modifying treatment and diversity of treatment pathways in relapsing remitting multiple sclerosis.

BACKGROUND: There is minimal information on the utilisation of Disease Modifying Treatment (DMTs) for multiple sclerosis. The appropriate and safe use of medicines is informed by utilisation studies. Outcomes can inform health interventions to improve appropriate use of medicines and post marketing surveillance activities to improve safety. OBJECTIVE: To evaluate utilisation and treatment patterns of disease modifying treatments (DMTs) for relapsing remitting multiple sclerosis (RRMS). METHODS: A representative sample of the Australian pharmaceutical benefits scheme data were analysed (2006-2016). Demographics of incident users and trends in incident and prevalent users were determined. Individual patient treatment pathways were determined by sequential initiation of medicines in two different periods (2006-2013 and 2014-2019). RESULTS: There were 20,660 patients with at least one dispensing of a DMT for RRMS during the study period (median age 41 years, 75% female). Incident and prevalent use increased by 20% and 88%, respectively. The market was responsive to 13 new listings of DMTs over the study period. Sequential treatment was found for 66% of initiators in 2006-2013 and 28.5% of initiators in 2014-2019. Diverse treatment pathways were found, with 278 and 93 unique sequences in 2006-2013 and 2014-2019, respectively. CONCLUSION: The availability of new DMTs has influenced both initial treatment choice and prevalence of users. Individualised treatment patterns and exposure to multiple medicines over time will challenge traditional pharmacovigilance systems.

Progressive kidney failure in chronic myelomonocytic leukaemia: don't forget lysozyme damage.

Kidney failure is common in haematologic malignancies. However, the nephrotoxic effect of lysozyme is seldom recognized. We present a 78-year-old male with chronic myelomonocytic leukaemia who developed progressive kidney failure due to increased production of lysozyme.

Performance and precision of double digestion RAD (ddRAD) genotyping in large multiplexed datasets of marine fish species.

The development of Genotyping-By-Sequencing (GBS) technologies enables cost-effective analysis of large numbers of Single Nucleotide Polymorphisms (SNPs), especially in "non-model" species. Nevertheless, as such technologies enter a mature phase, biases and errors inherent to GBS are becoming evident. Here, we evaluated the performance of double digest Restriction enzyme Associated DNA (ddRAD) sequencing in SNP genotyping studies including high number of samples. Datasets of sequence data were generated from three marine teleost species (>5500 samples, >2.5 × 1012 bases in total), using a standardized protocol. A common bioinformatics pipeline based on STACKS was established, with and without the use of a reference genome. We performed analyses throughout the production and analysis of ddRAD data in order to explore (i) the loss of information due to heterogeneous raw read number across samples; (ii) the discrepancy between expected and observed tag length and coverage; (iii) the performances of reference based vs. de novo approaches; (iv) the sources of potential genotyping errors of the library preparation/bioinformatics protocol, by comparing technical replicates. Our results showed use of a reference genome and a posteriori genotype correction improved genotyping precision. Individual read coverage was a key variable for reproducibility; variance in sequencing depth between loci in the same individual was also identified as an important factor and found to correlate to tag length. A comparison of downstream analysis carried out with ddRAD vs single SNP allele specific assay genotypes provided information about the levels of genotyping imprecision that can have a significant impact on allele frequency estimations and population assignment. The results and insights presented here will help to select and improve approaches to the analysis of large datasets based on RAD-like methodologies.

A substudy evaluating treatment intensification on medication adherence among hypertensive patients receiving home blood pressure telemonitoring and pharmacist management.

WHAT IS KNOWN AND OBJECTIVE: Hypertension is a leading cause of death and major contributor to heart attacks, strokes, heart and kidney failure. Antihypertensive (HTN medication) non-adherence contributes to uncontrolled hypertension. Effective initiatives to improve uncontrolled hypertension include a team-based approach with home blood pressure (BP) monitoring. Our study objective was to evaluate whether objectively measured medication adherence was influenced by home BP telemonitoring and pharmacist management. METHODS: We analysed HTN medication adherence in 240 patients who received home BP telemonitoring and pharmacist intervention (TI). Adherence was measured based on prescription fills and the proportion of days covered (PDC). HTN medications continued pre- to post-baseline were similar for telemonitoring intervention (TI) and usual care (UC) patients (rate ratio = 1·00, P = 0·90). RESULTS AND DISCUSSION: More HTN medications were discontinued pre- to post-baseline in TI patients (rate ratio = 1·38, P = 0·04). Similarly, more HTN medications were added in TI patients (rate ratio = 2·46, P < 0·001). The proportion with a mean PDC ≥ 0·8 for HTN medications added after baseline and overall adherence did not differ between groups. WHAT IS NEW AND CONCLUSION: Medication adherence was high in both groups; however, medication adherence was not significantly altered by the intervention. There were more medication modifications and greater medication intensification among TI patients.

Outpatient diabetes clinical decision support: current status and future directions.

Outpatient clinical decision support systems have had an inconsistent impact on key aspects of diabetes care. A principal barrier to success has been low use rates in many settings. Here, we identify key aspects of clinical decision support system design, content and implementation that are related to sustained high use rates and positive impacts on glucose, blood pressure and lipid management. Current diabetes clinical decision support systems may be improved by prioritizing care recommendations, improving communication of treatment-relevant information to patients, using such systems for care coordination and case management and integrating patient-reported information and data from remote devices into clinical decision algorithms and interfaces.

Fenofibrate-associated changes in renal function and relationship to clinical outcomes among individuals with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) experience.

AIMS/HYPOTHESIS: Fenofibrate has been noted to cause an elevation in serum creatinine in some individuals. Participants in the Action to Control Cardiovascular Risk in Diabetes Lipid Study were studied to better characterise who is at risk of an increase in creatinine level and to determine whether those with creatinine elevation have a differential risk of adverse renal or cardiovascular outcomes. METHODS: A fenofibrate-associated creatinine increase (FACI) was defined as an increase in serum creatinine of at least 20% from baseline to month 4 in participants assigned to fenofibrate. Baseline patient characteristics, and baseline and 4-month drug, clinical, laboratory characteristics and study outcomes were examined by FACI status. RESULTS: Of the sample, 48% of those randomised to receive fenofibrate had at least a 20% increase in serum creatinine within 4 months. In multivariable analysis, participants who were older, male, used an ACE inhibitor at baseline, used a thiazolidinedione (TZD) at 4 months post-randomisation, had baseline CVD, and had lower baseline serum creatinine and LDL-cholesterol levels were all more likely to meet the criteria for FACI. Participants in the FACI group were also more likely to have a decrease in their serum triacylglycerol level from baseline to 4 months. No differences in study outcomes were seen by FACI criteria. CONCLUSIONS/INTERPRETATION: Several characteristics predict a rapid rise in serum creatinine upon starting fenofibrate. Participants who met the criteria for FACI also had a greater change in triacylglycerol levels. In the setting of careful renal function surveillance and reduction of fenofibrate dose as indicated, no increase in renal disease or cardiovascular outcome was seen in those individuals demonstrating FACI. TRIAL REGISTRATION: ClincalTrials.gov: NCT00000620. FUNDING: The ACCORD Trial was supported by grants (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035 and IAA-Y1-HC-1010) from the National Heart, Lung, and Blood Institute; by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute; by the Centers for Disease Control and Prevention; by General Clinical Research Centers and by the Clinical and Translational Science Awards. Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca Pharmaceuticals LP, Bayer HealthCare LLC, Closer Healthcare, GlaxoSmithKline Pharmaceuticals, King Pharmaceuticals, Merck, Novartis Pharmaceuticals, Novo Nordisk, Omron Healthcare, sanofi-aventis US and Takeda Pharmaceuticals provided study medications, equipment or supplies.

Improving diabetes care in a large health care system: an enhanced primary care approach.

OBJECTIVE: The objective of this study was to evaluate the impact of a multifaceted improvement strategy on diabetes quality of care in a defined population of patients. STUDY DESIGN: A multifaceted improvement strategy to enhance diabetes care was deployed to 18 primary care clinics serving 170,000 adults. Interventions empowered patient self-management, supported care team decision making, redesigned office systems, and maximized use of available information technology. Specific goals were to improve glycemic control and reduce cardiovascular risk in all adult diabetes patients. DATA SOURCE AND COLLECTION: Diabetes was identified through pharmacy and diagnostic data (estimated sensitivity 0.91, positive predictive value 0.94), and the target population ranged from 6,542 to 7,037 members over time. Trends in glycosylated hemoglobin (HbA1c) and low-density lipid LDL-cholesterol were analyzed monthly throughout 1999 in both cohorts and serial cross-sections. RESULTS: During 12 months, mean HbA1c improved from 7.86% to 7.47%, and the proportion of patients with HbA1c levels < 8% rose from 60.5% to 68.3%, and the proportion with HbA1c > 10% fell from 10.3% to 7.2%. The LDL test rate rose from 47.4% to 57.4%, and mean LDL fell from 120 mg/dl to 116 mg/dl. The proportion with acceptable lipid control (LDL < 130 mg/dl, or < 100 mg/dl with coronary artery disease) rose from 48.9% to 57.7%. All changes were significant at p < 0.01 or less. CONCLUSION: Clinically significant population-based improvements in diabetes care were observed during a 1-year period using a multifaceted "enhanced primary care" strategy.

Human dirofilariasis.

BACKGROUND: Subcutaneous and pulmonary dirofilariasis in humans appears to be a frequent disease in endemic areas, notably the Mediterranean region. Following increased air travel in recent years, the incidence of human dirofilariasis has increased in tourists as well. METHODS: The clinical and parasitologic aspects in a series of six patients with cutaneous and pulmonary dirofilariasis, seen in a German unit for infectious and tropical diseases, are reviewed. RESULTS: Four patients presented with subcutaneous tumors due to infection with Dirofilaria repens, whereas two patients had pulmonary infiltrates due to the canine heartworm, D, immitis. All infections were acquired in the Mediterranean region. Symptoms were only slight and nonspecific. Eosinophilia in the blood was absent in all patients. The serum IgE levels were normal and signs of a specific humoral response to antigens of Dirofilaria spp. were absent, although slightly elevated antibody levels to antigens of Onchocerca volvulus could be demonstrated in all patients. The diagnosis was established in all patients by the surgical removal of adult worms from the lesions. Oral treatment with diethylcarbamazine (DEC) (2 mg per kg t.i.d.) over a period of 4 weeks was added to the surgical treatment in all patients. In one patient this therapy was preceded by oral ivermectine (150 mg per kg). CONCLUSIONS: Dirofilariasis has to be considered as a differential diagnosis in patients presenting with subcutaneous or pulmonary tumors after travels to endemic areas within the last few years. Effective therapy is possible by surgical removal of the adult worms and oral ivermectine plus diethylcarbamazine.

[Cost effectiveness of captopril after myocardial infarct; comment]. / Die Wirtschaftlichkeit von Captopril nach Myokardinfarkt.

BACKGROUND: In Germany approximately 88,000 people died as a result of acute myocardial infarction and approximately 300,000 people suffered from acute myocardial infarction in 1992. These data demonstrate the socioeconomic impact of coronary disease. In the SAVE-(Survival-and-Ventricular-Enlargement) study, Pfeffer et al. demonstrated a reduction of morbidity and mortality due to therapy with captopril in patients after myocardial infarction. In a retrospective, incremental cost-effectiveness-analysis, from the perspective of German statutory insurance fund, the economic impact of captopril after myocardial infarction has been analysed. PATIENTS AND METHOD: The basis for the economic evaluation has been the double-blind, placebo-controlled, clinical SAVE-study which included 2,231 patients having left ventricular dysfunction after acute myocardial infarction. Additional data e.g. average number of hospital days or average costs for hospitalisation per day was taken from published national statistical sources. In the cost-effectiveness-analysis, inputs (monetary units) and outputs (non-monetary units) were identified and measured. The cost-effectiveness (costs per life-year gained) demonstrates a relation between the costs of captopril-treatment, costs for myocardial infarction and costs for leftventricular insuffiency and the clinical benefit e.g. life years gained. RESULTS: Initially costs in the captopril-group are 3.7 Mio DM higher as in the placebo-group. But these costs are partly compensated by the cost reductions in the captopril-group, compared to the placebo-group (2,162,901 DM) the reduction of myocardial infarction and DM 556,518 cost reduction due to fewer patients with left ventricular dysfunction. The clinical benefit of the captopril treatment equals 495 life years gained. The cost-effectiveness-ratio is 2,000 DM cost for life year gained. CONCLUSION: The treatment with captopril after acute myocardial infarction is not only a clinically efficacious treatment, but also cost-effective in patients after acute myocardial infarction.