The effect of hypertension and hypercholesterolemia screening with subsequent intervention letter on the use of blood pressure and lipid lowering drugs

AIM: To evaluate the effect of a letter intervention that was send to both the participants of a population screening and their general practitioners. We also tested what predicting variables influenced the GP to actually prescribe blood pressure lowering drugs (BPLD) or lipid lowering drugs (LLD). METHOD: The study design was cross sectional, in the PREVEND outpatient clinic in Groningen University Hospital, the Netherlands. We used the clinical data of the 8592 subjects that participated in the first screening of the PREVEND study. Data on drug use was collected from community pharmacies. Drug use was measured the year before and after the screening with the subsequent intervention letter. As control population without intervention, we used the data from the InterAction DataBase (IADB) standardized for the population characteristics of the intervention group. The letter intervention was sent to participants who had shown after screening to have either an elevated blood pressure or plasma cholesterol, and the letter contained the advice to use a BPLD or LLD. Main outcome measures were proportion of patients prescribed BPLD and/or LLD in the year before and after the intervention, and variables that influence the GP to prescribe BPLD and LLD. RESULTS: Data from the community pharmacy were available from 7567 (88%) subjects. 397 participants (5.2%) received a letter with advice to start a BPLD, and 326 participants (4.3%) received a letter with advice to start a LLD. The prevalence of patients who were using BPLD and LLD before the intervention was not significantly different between the intervention and control group, 16.6 (CI 95% 15.8 -17.5) vs 16.0 and 4.8 (4.4-5.3) vs 4.6, respectively. After the letter intervention, the prevalence of BPLD use was higher in the intervention group compared with the control group (19.4 [18, 5-20, 3]vs 17.0%), as was the prevalence of LLD use (7.1[6.5-7.7) vs 5.4%). The same held true for the incidence of BPLD (3.4[3.0-3.8]vs 2.5%) and LLD use (2.1 [1, 6-2, 4]vs 1.0%), respectively, in the year after the intervention. Univariate and multivariate analysis showed that a higher blood pressure and cholesterol level, but not the presence of other cardiovascular risk factors, were associated to with a greater percentage use of a BPLD and a LLD. CONCLUSION: A population survey followed by a letter of intervention to both the patient and GP are effective to improve the use of blood pressure and lipid lowering drugs as a primary prevention in patients with hypertension and hyperlipidemia. Our therapeutic advice however, was followed only in about one of the three subjects with hypertension and one of the four subjects with hyperlipidemia. The levels of blood pressure and plasma total cholesterol are important variables influencing the GP to prescribe a BPLD and/or LLD.     

Anti-emetic drugs in oncology: pharmacology and individualization by pharmacogenetics

Objective Nausea and vomiting are the most distressful side effects of cytotoxic drugs in cancer patients. Antiemetics are commonly used to reduce these side effects. However, the current antiemetic efficacy is about 70?C80% in patients treated with highly-emetogenic cytotoxic drugs. One of the potential factors explaining this suboptimal response is variability in genes encoding enzymes and proteins which play a role in metabolism, transport and receptors related to antiemetic drugs. Aim of this review was to describe the pharmacology and pharmacogenetic concepts of of antiemetics in oncology. Method Pharmacogenetic and pharmacology studies of antiemetics in oncology published between January 1997 and February 2010 were searched in PubMed. Furthermore, related textbooks were also used for exploring the pharmacology of antiemetic drugs. The antiemetic drugs which were searched were the 5-hydroxytryptamine 3 receptor antagonists (5-HT3RAs), dopamine antagonists, corticosteroids, benzodiazepines, cannabinoids, antihistamines and neurokinin-1 antagonists. Result The 5-HT3RAs are widely used in highly emetogenic chemotherapy in combination with dexamethasone and a neurokinin-1 antagonist, especially in acute phase. However, the dopamine antagonists and benzodiazepines were found more appropriate for use in breakthrough and anticipatory symptoms or in preventing the delayed phase of chemotherapy induced nausea and vomiting. The use of cannabinoids and antihistamines need further investigation. Only six articles on pharmacogenetics of the 5-HT3RAs in highly emetogenic chemotherapy are published. Specifically, these studies investigated the association of the efficacy of 5-HT3RAs and variants in the multi drug resistance 1 (MDR1) gene, 5-HT3A,B and C receptor genes and CYP2D6 gene. The pharmacogenetic studies of the other antiemetics were not found in this review. Conclusion It is concluded that pharmacogenetic studies with antiemetics are sparse. It is too early to implement results of pharmacogenetic association studies of antiemetic drugs in clinical practice: confirmation of early findings is required.     

Pharmacogenetics of isoniazid-induced hepatotoxicity

Tuberculosis is still a major problem in some developed and developing countries. The poor compliance to the treatment of tuberculosis patients due to the adverse events was supposed to be an important factor contributing to the high prevalence. This review aims to clarify the role and the pharmacological mechanism of the genes involved in the isoniazid-induced hepatotoxicity. We selected English articles of studies in human from PubMed up to May 2014 with the keywords pharmacogenetic, isoniazid and hepatotoxicity, N-acetyl transferase 2 (NAT2), CYP2E1 and glutathione S transferase (GST). Polymorphisms of NAT2, CYP2E1 and GST1 could increase patients’ susceptibility to isoniazid-induced hepatotoxicity. The rapid acetylators of NAT2 and rapid metabolizers of CYP2E1 showed increased concentrations of hepatotoxic metabolites. However, the rapid metabolizers of GST1 could decrease the concentration of hepatotoxic metabolites. Some studies of human leukocyte antigen (HLA), Uridine 5′-dipphospho (UDP) glucuronosyltransferase (UGT), nitric oxide synthase (NOS), Broad complex, Tramtrack, Bric-a-brac (BTB) and cap'n'collar type of basic region leucine zipper factor family (CNC) homolog (BACH) and Maf basic leucine zipper protein (MAFK) polymorphisms showed their roles in isoniazid-induced hepatotoxicity by modifying the expression of antioxidant enzymes. A better insight into the role of polymorphisms of HLA, UGT, NOS, BACH and MAFK in addition to NAT2, CYP2E1 and GST1 in the hepatotoxicity of isoniazid may support physicians in monitoring patients hepatotoxicity symptoms and laboratory data and optimizing pharmacotherapy. Future studies about the role of such polymorphisms in different ethnicities are suggested.     

An economic assessment of losartan-based versus atenolol-based therapy in patients with hypertension and left-ventricular hypertrophy: results from the Losartan Intervention For Endpoint reduction (LIFE) study adapted to The Netherlands

BACKGROUND: The Losartan Intervention For Endpoint reduction (LIFE) study was a randomized, doubleblind trial that compared the effects of losartan-based treatment with those of atenolol-based treatment on cardiovascular disease (CVD)-related morbidity and mortality in 9193 patients with hypertension and left-ventricular hypertrophy (LVH). Compared with atenolol, losartan reduced the combined risk for CVD-related morbidity and mortality by 13% (P = 0.021), and reduced the risk for stroke by 25% (P = 0.001), with comparable blood pressure control in both trial arms. OBJECTIVE: The aim of this study was to analyze the cost-effectiveness of losartan compared with atenolol in the treatment of stroke from the Dutch health care perspective. METHODS: Utilization of losartan and atenolol within the trial period (mean, 4.8 years) and an estimation of direct medical costs of stroke for The Netherlands were combined with estimates of reduction in life expectancy through stroke. Medication costs and stroke incidence during 5.5 years of patient follow-up were estimated separately, adjusted for the baseline degree of LVH and Framingham risk score. To estimate lifetime stroke costs, the cumulative incidence of stroke was multiplied by the lifetime direct medical costs attributable to stroke. All costs are in 2006 Dutch prices and discounted following the former (4% costs and effects) and new Dutch guideline (4% costs, 1.5% effects) for conducting pharmacoeconomic analyses. RESULTS: With 4% discounting, prevention of stroke was associated with a gain of 3.7 life-years. As a consequence, losartan treatment was associated with 0.059 life-year gained (LYG) per patient treated with losartan. Losartan reduced stroke-related costs by 1,076 Euros (US $1,349) per patient. After inclusion of study medication cost, net cost per patient was 51 Euros ($64) higher for losartan than atenolol. The net cost per LYG was 864 Euros ($1083), which is below the Dutch pharmacoeconomic threshold of 20,000 Euros/LYG (~$25,000/LYG) for accepting interventions. The corresponding probability of a cost-effectiveness ratio below this Dutch threshold was 0.95. Discounting money and health following the new Dutch guideline resulted in an even more favorable cost-effectiveness for losartan. CONCLUSIONS: Results from the present analysis suggest that, in The Netherlands, treatment with losartan compared with atenolol may well be a cost-effective intervention based on the reduced risk for stroke observed in the LIFE trial.     

Nutritional status,exclusive breastfeeding and management of acute respiratory illness and diarrhea in the first 6 months of life in infants from two regions of Indonesia

Background

Infant morbidity and mortality rates remain high in Indonesia, with acute respiratory illnesses (ARI) and diarrhea the leading two health problems in children under 5 years. We aimed to describe the nutritional status, feeding practice and case management of ARI and diarrhea of infants from two regions of Indonesia during the first 6 months of life.

Methods

This study was an observational study conducted in parallel to an immunogenicity and efficacy trial of an oral rotavirus vaccine (RV3-BB) in the Klaten and Yogyakarta regions, Indonesia. Mothers were interviewed at 3 time points: within the first 6 days of their infant’s life, and at 8–10 and 22–24 weeks of age. Questions asked included pregnancy history, infant nutritional status, feeding status and health of infants within up to 2 weeks prior to the assessment.

Results

Between February 2013 and January 2014, 233 mother-infant pairs were recruited. 60% (136/223) of infants were exclusively breastfed (EBF) until 6 months of age with the strongest support for EBF reported by mothers themselves 70% (101/223) and 25% (36/223) from their partners. At 6 months, 6% (14/223) of infants were underweight and severely underweight; 4% (8/ 223) wasted and severely wasted; and 12% (28/223) were stunted and severely stunted. Non-recommended medication use was high, with 54% (21/39) of infants with reported cough within 2 weeks of an assessment receiving cough medication, 70% (27 /39) an antihistamine, 26% (10/39) a mucolytic and 15% (6 /39) an oral bronchodilator. At age 22–24 week, infants with reported diarrhea within 2 weeks of an assessment had low use of oral rehydration solutions (ORS) (3/21;14%) and zinc therapy (2/ 21;10%).

Conclusion

In this unique observational study, breastfeeding rates of 60% at 6 months were below the Indonesian national target of >75%. Adherence to WHO guidelines for management of ARI and diarrhea was poor, with high use of non-recommended cough medications and oral bronchodilators in the first 6 months of life and low use of ORS and zinc therapy. Ongoing education of primary health care workers and parents regarding management of common illness is needed in Indonesia.

     

The impact of hormonal contraceptives on blood pressure, urinary albumin excretion and glomerular filtration rate

AIM: In short-term studies, hormonal contraceptives (HC) have been suggested to induce a rise in blood pressure (BP) and urinary albumin excretion (UAE), while the effect of HC in renal function (GFR) is still under debate. Data on long-term and withdrawal effects of HC use on these outcomes are, however, not available. We therefore studied whether the start and cessation of HC induce changes in BP, UAE and GFR. METHODS: We used data from the PREVEND Study, a prospective cohort of subjects aged 28-75 years. Eligible were women aged < or = 45 years with complete clinical and pharmacy data on baseline and follow-up screening (4 years later). Multivariate regression analysis was used to estimate the effects of HC on BP, UAE and GFR in those who started (n = 73), stopped (n = 117) or continued (n = 183) with those who never used HC (n = 286) as the reference group. RESULTS: BP increased among starters and fell in stoppers. These changes compared with never-users were statistically significant, even after adjustment for relevant variables. UAE increased by 14.2% in starters (P = 0.074) and fell by 10.6% in stoppers (P = 0.021), while GFR fell by 6.3% in starters (P < 0.001) and did not change in stoppers. The effects of stopping HC on UAE and GFR were significantly different compared with changes among never-users, even after adjustment for other variables (P = 0.023 and 0.036, respectively). CONCLUSIONS: The start of HC was independently associated with worsening of BP, UAE and GFR, while stopping HC use resulted in an improvement. These data suggest that long-term HC use (aged 28-45 years) may be deleterious from the cardiovascular and renal point of view, but stopping may result in correction of these effects.