Comparing the EQ-5D-3 L and EQ-5D-5 L: studying measurement and scores in Indonesian type 2 diabetes mellitus patients.

BACKGROUND: The EuroQoL five-dimensional instrument (EQ-5D) is the favoured preference-based instrument to measure health-related quality of life (HRQoL) in several countries. Two versions of the EQ-5D are available: the 3-level version (EQ-5D-3 L) and the 5-level version (EQ-5D-5 L). This study aims to compare specific measurement properties and scoring of the EQ-5D-3 L (3 L) and EQ-5D-5 L (5 L) in Indonesian type 2 diabetes mellitus (T2DM) outpatients. METHODS: A survey was conducted in a hospital and two primary healthcare centres on Sulawesi Island. Participants were asked to complete the two versions of the EQ-5D instruments. The 3 L and 5 L were compared in terms of distribution and ceiling, discriminative power and test-retest reliability. To determine the consistency of the participants' answers, we checked the redistribution pattern, i.e., the consistency of a participant's scores in both versions. RESULTS: A total of 198 T2DM outpatients (mean age 59.90 ± 11.06) completed the 3 L and 5 L surveys. A total of 46 health states for 3 L and 90 health states for 5 L were reported. The '11121' health state was reported most often: 17% in the 3 L and 13% in the 5 L. The results suggested a lower ceiling effect for 5 L (11%) than for 3 L (15%). Regarding redistribution, only 6.1% of responses were found to be inconsistent in this study. The 5 L had higher discriminative power than the 3 L version. Reliability as reflected by the index score was 0.64 for 3 L and 0.74 for 5 L. Pain/discomfort was the dimension mostly affected, whereas the self-care dimension was the least affected. CONCLUSIONS: This study suggests that the 5 L-version of the EQ-5D instrument performs better than the 3 L-version in T2DM outpatients in Indonesia, regarding measurement and scoring properties. As such, our study supports the use of the 5 L as the preferred health-related quality of life measurement tool. We did not do a trial but this study was approved by the Medical Ethics Committee of Universitas Gadjah Mada Yogyakarta, Indonesia (document number KE/FK/1188/EC, 12 November 2014, amended 16 March 2015).

'Diabetes is a gift from god' a qualitative study coping with diabetes distress by Indonesian outpatients.

BACKGROUND: More than two-thirds of patients diagnosed with type 2 diabetes mellitus (T2DM) in Indonesia encounter medical-related problems connected to routine self-management of medication and the social stigma related to T2DM. The current study aims to explore distress and coping strategies in Indonesian T2DM outpatients in a Primary Healthcare Centre (PHC) in Surabaya, East Java, Indonesia. METHODS: We conducted a qualitative study using two different data collection methods: focus group discussions and in-depth interviews. The guideline of interviews and discussions were developed based on seventeen questions derived from the DDS17 Bahasa Indonesia (a Bahasa Indonesia version of the Diabetes Distress Scale questionnaire), which covered physician distress domain, emotional burden domain, regimen distress domain and interpersonal distress domain. RESULTS: The majority of the 43 participants were females and aged 50 or older. Our study discovered two main themes: internal and external diabetes distress and coping strategies. Internal diabetes distress consists of disease burden, fatigue due to T2DM, fatigue not due to T2DM, emotional burden (fear, anxiety, etc.) and lack of knowledge. Internal coping strategies comprised spirituality, positive attitude, acceptance and getting more information about T2DM. External diabetes distress was evoked by distress concerning healthcare services, diet, routine medication, monthly blood sugar checks, interpersonal distress (family) and financial concern. External coping strategies included healthcare support, traditional medicine, vigilance, self-management, social and family support and obtaining information about health insurance. CONCLUSION: Our study shows that for Indonesian T2DM-patients, spirituality and acceptance are the most common coping mechanisms for reducing DD. Furthermore, our study revealed an overall positive attitude towards dealing with T2DM as well as a need for more information about T2DM and potential coping strategies. Finally, an important finding of ours relates to differences in DD between males and females, potential DD associated with health services provision and the specific challenges faced by housewives with T2DM.

Diabetes distress in Indonesian patients with type 2 diabetes: a comparison between primary and tertiary care.

BACKGROUND: The number of people living with diabetes mellitus (DM) in Indonesia has continued to increase over the last 6 years. Four previous studies in U.S have found that higher DD scores were associated with worse psychological outcomes, lower health-related quality of life (HRQoL) and increased risk of T2DM complications. In this study, we aimed to firstly compare DD scores in Indonesian T2DM outpatients treated in primary care versus those in tertiary care. Subsequently, we investigated whether socio-demographic characteristics and clinical conditions explain potential differences in DD score across healthcare settings. METHODS: A cross-sectional study was conducted on Java island in three primary care (n = 108) and four tertiary care (n = 524) facilities. The participants completed the Bahasa Indonesia version of the Diabetes Distress Scale questionnaire (DDS17 Bahasa Indonesia). Ordinal regression analysis was conducted with the quartile of the summation of the DD score as the dependent variable to investigate how the association between the level of healthcare facilities and DD altered when adding different variables in the model. RESULTS: The final adjusted model showed that the level of healthcare facilities was strongly associated with DD (p < .001), with participants in primary care having a 3.68 times (95% CI 2.46-5.55) higher likelihood of being more distressed than the participants in tertiary care. This association was detected after including the socio-demographic characteristics and clinical conditions as model confounders. CONCLUSIONS: This is the first study in Indonesia to compare DD scores within different healthcare facilities. We recommend a regular DD assessment, possibly closely aligned with health-literacy partner programs, especially for T2DM patients in primary care settings.

Religious and community leaders' acceptance of rotavirus vaccine introduction in Yogyakarta, Indonesia: a qualitative study.

BACKGROUND: In Indonesia, oral rotavirus vaccines are available but not funded on the National Immunization Program (NIP). New immunization program introduction requires an assessment of community acceptance. For religiously observant Muslims in Indonesia, vaccine acceptance is further complicated by the use of porcine trypsin during manufacturing and the absence of halal labeling. In Indonesia, religious and community leaders and the Majelis Ulama Indonesia (MUI) are important resources for many religiously observant Muslims in decisions regarding the use of medicines, including vaccines. This study aimed to explore the views of religious and community leaders regarding the rotavirus vaccine to inform future communication strategies. METHODS: Twenty semi-structured in-depth interviews were undertaken with religious leaders and community representatives from two districts of Yogyakarta Province, Indonesia. Thematic analysis was undertaken. RESULTS: Although there was recognition childhood diarrhoea can be severe and a vaccine was needed, few were aware of the vaccine. Participants believed a halal label was required for community acceptance, and maintenance of trust in their government and leaders. Participants considered themselves to be key players in promoting the vaccine to the community post-labeling. CONCLUSIONS: This study highlights the need for better stakeholder engagement prior to vaccine availability and the potentially important role of religious and community leaders in rotavirus vaccine acceptability in the majority Muslim community of Yogyakarta, Indonesia. These findings will assist with the development of strategies for new vaccine introduction in Indonesia.

The Development of Quality of Life Questionnaire for Indonesian Breast Cancer Patients: INA-BCHRQoL

Introduction: The breast cancer related incidence and mortality rate in Indonesia are included in the top 10 and top 5 highest in the world. A country-specific Health Related Quality of Life measurement tool is required to help clinician observe and improve the management of the disease. Methods: We developed the questionnaire, namely Indonesian Breast Cancer Health Related Quality of Life (INA-BCHRQoL) by incorporating not only the generic variables such as physical, psychological, and social; but also spiritual variable which is suitable for Indonesian population. The questionnaire was validated to the same population using the value of corrected item-total correlation and the value of Cronbach Alpha. Results: Fourty three questions were considerably valid and reliable on evaluating the HRQoL of early state of breast cancer patients in Indonesia as the value of Cronbach Alpha for physical, cognitive, social and spiritual domain were higher than 0.8 and the corrected item-total correlation were also higher than 0.3. Each domain of the questionnaire was not influenced by the treatment options. Twenty four early stage breast cancer (10 FAC based chemotherapy and 14 Taxan based chemotherapy) were enrolled in the main study and the score of HRQOL obtained from INA-BCHRQoL were considerably high. Conclussion: The INA-BCHRQoL questionnaire can be implemented as a valid and reliable tool to assess quality of life in early stage breast cancer patients in Indonesia.

Knowledge and attitudes towards rotavirus diarrhea and the vaccine amongst healthcare providers in Yogyakarta Indonesia.

BACKGROUND: Rotavirus has been identified as the most common pathogen associated with severe diarrhoea. Two effective vaccines against the pathogen have been licensed. However, many countries including Indonesia have yet to introduce the vaccine into their national immunisation programs. This study aimed to examine the attitudes of healthcare providers (HCPs) and other health stakeholders towards the pathogen and the vaccine. METHODS: Semi-structured in-depth interviews were undertaken in two districts of Yogyakarta Province, Indonesia with nurses, midwives, primary care providers, pediatricians and other health stakeholders. Thematic analysis was undertaken. RESULTS: Fourteen interviews were conducted between August and October 2013. We identified that while participants do not consider diarrhea to be an important problem in Indonesia, they do acknowledge that it can be serious if not properly treated. While the majority had some level of knowledge about rotavirus, not all participants knew that a vaccine was available. There were mixed feelings towards the need for the vaccine. Some felt that the vaccine is not ranked as a priority as it is not listed on the national program. However, others agreed there is a rationale for its use in Indonesia. The cost of the vaccine (when sold in the private sector) was perceived to be the primary barrier impacting on its use. CONCLUSIONS: The high cost and the low priority given to this vaccine by the public health authorities are the biggest obstacles impacting on the acceptance of this vaccine in Indonesia. HCPs need to be reminded of the burden of disease associated with rotavirus. In addition, reminding providers about the costs associated with treating severe cases versus the costs associated with prevention may assist with improving the acceptance of HCPs towards the vaccine. Promotion campaigns need to target the range of HCPs involved in the provision of care to infants and pregnant women.

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.

The cost-effectiveness of HPV vaccination in addition to screening: a Dutch perspective.

Addition of the HPV vaccine to available cytological screening has been proposed to increase HPV-related cancer prevention. A comprehensive review on this combined strategy implemented in the Netherlands is lacking. For this review, we therefore analyzed all relevant studies on cost-effectiveness of HPV vaccines in combination with cervical screening in the Netherlands. Most of the studies agree that vaccination in pre-sexual-activity periods of life is cost-effective. Based on published sensitivity analyses, the incremental cost-effectiveness ratio was found to be mainly driven by vaccine cost and discount rates. Fewer vaccine doses, inclusion of additional benefits of these vaccines to prevent HPV-related non-cervical cancers and vaccination of males to further reduce the burden of HPV-induced cancers are three relevant options suggested to be investigated in upcoming economic evaluations.

Impact of chemotherapy-induced nausea and vomiting on quality of life in indonesian patients with gynecologic cancer.

BACKGROUND: Quality of life (QoL) has become a major outcome in the treatment of patients with cancer. This study is aimed at examining the impact of chemotherapy-induced nausea and vomiting on QoL of patients with gynecologic cancer in Indonesia. METHODS: Chemotherapy-naive patients with gynecologic cancer, who were treated with cisplatin at a dosage 50 mg/m or higher as monotherapy or as part of combination chemotherapy regimens, were recruited in the Oncology Department, Dr. Sardjito Hospital, Yogyakarta, Indonesia. Quality of life was assessed by using the Indonesian version of the European Organization for Research and Treatment for Cancer of Quality of Life Questionnaire and Short Form-36, administered immediately before and on day 5 after chemotherapy administration. Patients used a daily diary to record nausea and vomiting during 5 days after chemotherapy. RESULTS: Most (74.9%) of the 179 patients experienced delayed emesis during the 5 days after chemotherapy despite prophylactic use of antiemetics. The delayed nausea and emesis caused significant negative impact on patients' QoL. Nausea in the delayed phase caused negative effects on patients' QoL. CONCLUSIONS: Patients reported a negative impact on the QoL of delayed emesis after chemotherapy. Poor prophylaxis of patients' nausea and vomiting after chemotherapy interferes with patients' QoL. Medical and behavioral interventions may help to alleviate the negative consequences of chemotherapeutic treatment in patients with gynecologic cancers treated with suboptimal antiemetics.

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 70-80% 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.

Translation and validation of EORTC QLQ-C30 into Indonesian version for cancer patients in Indonesia.

OBJECTIVE: Quality of life studies in Indonesia are still uncommon. This research was aimed to validate the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 in Indonesian version. The standard procedure of forward-backward translation was adhered to in the translation procedures. The validity procedure included reliability, convergent and discriminant validity, known-groups validity, factor analysis and external convergent validity. METHODS: Data were collected from cancer patients in the Oncology Department of Sardjito Hospital, Yogyakarta, Indonesia, who were treated with cisplatin at the dosage ≥50 mg/m(2) as monotherapy or in combinations. The Short Form-36 was used to assess the external convergent validity of our translated questionnaire. RESULTS: One hundred and twenty-eight patients were recruited from March 2009 to November 2009. The internal consistency with values of >0.70 was observed in the Indonesian version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 scales. All items in the questionnaire met the criteria of convergent and discriminant validity, except for items 5. Both of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and the Short Form-36 showed that different diagnoses were associated with a similar impact on quality of life. Factor analysis showed that only the role function and social function loaded onto the second factor together. Correlations between the Indonesian versions of both questionnaires were moderate: between 0.18 and 0.48 for the physical, emotional, social, fatigue and pain domains. CONCLUSIONS: The Indonesian version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 can be used as a questionnaire to assess quality of life in Indonesian cancer patients with high-emetogenic treatments.

Baseline albuminuria predicts the efficacy of blood pressure-lowering drugs in preventing cardiovascular events.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Albuminuria has been proven to be associated with cardiovascular morbidity and mortality. Such an association has been found not only in subjects with diabetes and hypertension, but also in the general population. It could therefore be expected that especially subjects with higher albuminuria levels may benefit from blood pressure-lowering agents to improve their cardiovascular outcome. WHAT THIS STUDY ADDS: This study indicates that the efficacy of blood pressure-lowering agents to prevent cardiovascular events is dependent of the level of albuminuria before start of such treatment. The higher baseline albuminuria, the better the relative and absolute risk reduction for cardiovascular events with blood pressure-lowering drugs. The data also suggest a possible better cardiovascular protective effect of renin-angiotensin intervening agents compared with other blood pressure-lowering agents. AIMS: Albuminuria has been proven to be associated with cardiovascular (CV) events in specific patient populations, but also in the general population. This study aimed to investigate whether the efficacy of blood pressure-lowering agents in preventing CV events depends on baseline urinary albumin excretion (UAE) and, if so, whether this holds true for blood pressure-lowering agents in general, or is limited to agents that interfere in the renin-angiotensin system. METHODS: Data were used from a community-based cohort study and pharmacy dispensing records. Included were subjects with hypertension (systolic blood pressure >or=140 and/or diastolic blood pressure >or=90 mmHg), no cardiovascular disease history, and no previous use of blood pressure-lowering agents. RESULTS: During study follow-up (7.1 +/- 1.6 years), 122 CV events were observed in 1185 subjects included. Start of blood pressure-lowering agents vs. non-use was associated with a difference in absolute CV event risk of 0.7%, 6% and 12.6% for all subjects, those with UAE >or= 15 mg day(-1) and >or=30 mg day(-1), respectively. Cox regression analysis showed that the relative risk for CV events after start of blood pressure-lowering agents was significantly dependent (P < 0.05) on baseline UAE; with hazard ratios of 0.87 [95% confidence interval (CI) 0.48, 1.60, P = NS], 0.58 (95% CI 0.36, 0.94, P < 0.05) and 0.37 (95% CI 0.20, 0.68, P < 0.05), for subjects with UAE < 15, >or=15 and >or=30 mg day(-1), respectively. Results adjusted for covariates were essentially similar. The use of angiotensin converting enzyme inhibitor/angiotensin-II receptor blocker (ACEi/ARB) treatment tended to be associated with a more favourable CV prognosis when compared with non-ACEi/ARB treatment (difference P = 0.06). CONCLUSIONS: Our results suggest that the efficacy of blood pressure-lowering agents to prevent CV events is dependent on baseline albuminuria. The higher baseline albuminuria, the more absolute as well as relative risk reduction can be achieved. Our data suggest that this may especially be true for ACEi/ARBs. We caution that this is an observational study, and that these conclusions should therefore be regarded as hypothesis generating, rather than hypothesis testing.

The effect of screening for cardio-renal risk factors on drug use in the general population.

AIM: To evaluate the effect of a cardio-renal screening programme on desired and undue drug use. METHODS: Data from the PREVEND cohort (Prevention of REnal and Vascular ENd-stage Disease) were used. The drug use of screened (randomly) selected subjects (n = 2650) was compared with unscreened subjects, matched for age and sex (n = 10 434). Drug use in the overall PREVEND cohort, enriched for albuminuria (n = 6751), was also studied. Screening-related drugs (antihypertensive, antilipidaemic, antidiabetic and antithrombotic) were selected, as well as screening-unrelated drugs (benzodiazepines, drugs for acid-related disorders and painkillers). Time to first prescription after screening is presented as Kaplan-Meier curves. RESULTS: After 6.5 years of follow-up, the incidence of drug use was not significantly different between the screened, randomly selected and unscreened cohorts. Antihypertensives were used by 21.5 and 20.8%, respectively; antilipidaemic 12.8 and 10.2%, antidiabetics 4.0 and 3.9%, and antithrombotic 11.4 and 12.0%. Screening-unrelated drugs were used at comparable frequencies. Compared with the unscreened cohort, screening-related drugs were prescribed more frequently for subjects in the enriched cohort (25.8, 15.5, 5.5 and 13.5% for antihypertensive, antilipidaemic, antidiabetic and antithrombotic, respectively), whereas screening-unrelated drugs were used at comparable frequencies. CONCLUSIONS: The incidence of drug use did not differ between the screened, randomly selected and unscreened cohorts. Screening does not lead to more drug prescription, thus arguing against the fear of undue medicalization after screening. The data also show that, for screening to be successful, it should be performed in a targeted population, such as one enriched for albuminuria.

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.

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.

What predicts progression and regression of urinary albumin excretion in the nondiabetic population?

An increase or decrease in urinary albumin excretion (UAE) is associated with, respectively, a higher or lower risk for renal and cardiovascular disease, independent of widely known cardiovascular risk factors. This study aimed to identify factors that are associated with changes in UAE in the nondiabetic population using data of the Prevention of Renal and Vascular End stage Disease (PREVEND) Study, a community-based prospective cohort study. Data of the 6647 nondiabetic participants who completed the first (1997 through 2001) and second (2001 through 2003) screening were used. Change in UAE was categorized as regression (n = 650), stable (n = 5240), or progression (n = 757) on the basis of change in class during follow-up, with classes being a UAE <15, 15 to 30, 30 to 300, and >300 mg/24 h. With the use of stepwise forward multinomial regression analysis changes in BP, fasting glucose concentration, and start of antihypertensive drugs were found to be the most important modifiable variables associated with the risk for progression and regression (P < 0.01 for likelihood ratio test). The odds ratios to develop regression or progression of UAE during follow-up were 0.64 (95% confidence interval [CI] 0.57 to 0.73) and 1.91 (95% CI 1.72 to 2.12), respectively, per 10-mmHg increase in BP during follow-up, 0.89 (95% CI 0.80 to 0.98) and 1.09 (95% CI 1.01 to 1.17), respectively, per 1-mmol/L increase of fasting glucose levels during follow-up, and 1.57 (95% CI 1.21 to 2.06) and 0.70 (95% CI 0.51 to 0.95), respectively, for start of antihypertensive drugs during follow-up. These associations were independent of baseline BP, glucose, body mass index, estimated GFR, and UAE and changes in high-sensitivity C-reactive protein during follow-up. In conclusion, changes in glucose concentration and BP and start of antihypertensive drugs (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers in >50% of cases) are associated with progression and regression of UAE in the nondiabetic population. Although associations do not necessarily suggest causality, it is hypothesized that in the general population, the most important ways to reduce UAE are by lowering glucose concentration and BP (including start of antihypertensive medication), even in normotensive, nondiabetic individuals.

Pharmacoeconomics of angiotensin II antagonists in type 2 diabetic patients with nephropathy: implications for decision making.

Angiotensin II receptor antagonists (angiotensin II receptor blockers; ARBs) are a class of antihypertensive drugs that are generally considered comparable to ACE inhibitors in the prevention of heart and kidney failure. However, these two classes of agents do interfere in different stages of the renin-angiotensin system. In patients with type 2 diabetes mellitus, advantages for ARBs over conventional (non-ACE inhibitor) therapy on progression from micro- to macroalbuminuria and overt nephropathy and end-stage renal disease have been shown in clinical trials. In patients with type 2 diabetes and end-stage renal disease, the need for dialysis and/or transplantation results in the use of major healthcare resources. This paper reviews the available economic evidence on treatment with ARBs in type 2 diabetic patients with advanced renal disease.Within-trial analytic and Markov model economic evaluations of the RENAAL (Reduction of Endpoint in Non-insulin dependent diabetes mellitus with Angiotensin II Antagonist Losartan), IDNT (Irbesartan Diabetic Nephropathy Trial) and IRMA (IRbesartan in type 2 diabetes with MicroAlbuminuria)-2 studies suggest that treatment with ARBs in patients with type 2 diabetes with overt or incipient nephropathy confers health gains and net cost savings compared with conventional (non-ACE inhibitor) therapy. For reimbursement and reference pricing decisions, there is a need for a head-to-head comparison of an ACE inhibitor with ARBs to model all possible costs and effects of ACE inhibitors and ARBs. This will result in a proper pharmacoeconomic outcome, where both types of drugs can be compared for healthcare decisions.

Cost-effectiveness of screening for albuminuria with subsequent fosinopril treatment to prevent cardiovascular events: A pharmacoeconomic analysis linked to the prevention of renal and vascular endstage disease (PREVEND) study and the prevention of renal and vascular endstage disease intervention trial (PREVEND IT).

OBJECTIVE: This study estimated the cost-effectiveness,from the Dutch health care perspective, of screening for albuminuria in the general Dutch population to prevent cardiovascular events (CVEs) with subsequent angiotensin-converting enzyme inhibitor treatment, using data from the Prevention of REnal and Vascular ENdstage Disease Intervention Trial (PREVEND IT). METHODS: PREVEND IT was a single-center, double-blind, randomized, placebo-controlled trial with a 2 x 2 factorial design within the larger observational Prevention of REnal and Vascular ENdstage Disease (PREVEND) study. The PREVEND IT study was conducted to assess the effects of fosinopril 20 mg and pravastatin 40 mg on CVEs in subjects with specific inclusion criteria: urinary albumin excretion (UAE) rate in the range from 15 to 300 mg/d, blood pressure <160/100 mm Hg, and plasma cholesterol level <8.0 mmol/L. Cost-effectiveness estimates for the Dutch population were expressed in euros (2002; 1 euro = US 1.01 dollars) as net costs per life-year gained (LYG) in the baseline and sensitivity (stochastic) analyses. RESULTS: Data were assessed for 864 subjects, with a mean (SD) follow-up of 46 (7) months. CVEs occurred in 45 (5.2%) subjects. Subjects who received fosinopril had a 40% lower incidence of CVEs than subjects in the placebo group (3.9% vs 6.5%, respectively; P = NS). The cost-effectiveness of screening for albumnuria was determined to be euro 16,700/LYG for the study population. Stochastic analysis indicated that the probability of the cost-effectiveness being below the suggested Dutch threshold of euro 20,000/LYG was 59% in the baseline analysis. The probability of cost-effectiveness below euro 20,000/LYG would increase to 91% if only subjects with UAE >50 mg/d were treated with fosinopril. Limiting the screening to subjects aged >50 years and >60 years also improved cost-effectiveness. CONCLUSIONS: The results of our study suggest that screening the general Dutch population for albuminuria and subsequently treating those found positive with fosinopril may be cost-effective compared with no screening and adopting the Dutch health care perspective. However, confirmation from larger multicenter trials is needed.

The effect of statins on urinary albumin excretion and glomerular filtration rate: results from both a randomized clinical trial and an observational cohort study.

BACKGROUND: Statins improve cardiovascular outcome, but less is known on the renal outcome. We, therefore, studied the relationship between the use of statins and urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in two settings: a randomized controlled trial (RCT) and an observational cohort study, in which patients were included to study the impact of an elevated UAE on renal and cardiovascular prognosis. METHODS: We used data from the Prevention of REnal and Vascular ENd-stage Disease Intervention trial (PREVEND-IT) and the PREVEND cohort study. The PREVEND-IT subjects (788 with a UAE 15-300 mg/day) received pravastatin 40 mg/day vs placebo and/or fosinopril 20 mg/day vs placebo in a 2x2 factorial-RCT design. Of the 3440 cohort subjects, 469 used statins during the 4-year follow-up period. Multivariate-regression adjusted for confounding factors and the propensity score was used to estimate the relation between statin use and UAE and GFR. RESULTS: In the RCT, pravastatin did not change UAE or GFR, neither in fosinopril yes/no subgroups. In the observational cohort, statin use was associated with a rise in UAE (+12.1%), compared with statin non-use (+3.6%, P<0.001). This rise was most pronounced in those on statins prior to the first screening [+24.8% (95% CI: 11.9-39.2)], those using statins>3 years [+18.5% (7.3-30.8)] and those with >1 or >2 defined daily doses (+15.7 and +17.3%, respectively). These differences remained significant after adjustment for relevant variables and propensity score. The rise in UAE could not be attributed to a higher dose or a specific statin. GFR fell in 4 years in both statin users and non-users (4.6+/-13.5 and 2.4+/-11.2, respectively). The fall in GFR between groups was not different after adjustment (P=0.11). CONCLUSIONS: We conclude from the RCT data that statins do not lower UAE in subjects selected because of an elevated UAE instead of hyperlipidaemia. In the observational cohort study, the use of statins similarly was not associated with a fall in UAE; UAE instead increased. Statin treatment was not associated with a significant change in GFR in these subjects with only modestly impaired GFR.

Adherence of pharmacoeconomic studies to national guidelines in the Netherlands.

OBJECTIVE: This study examines the adherence of Dutch pharmacoeconomic studies to the national guidelines of conducting a pharmacoeconomic evaluation. METHODS: Dutch guidelines for pharmacoeconomic research were issued in 1999. All Dutch pharmacoeconomic studies that were published in English during 2000-2002 were selected for our review. Two reviewers examined each study for relevance and compared each study with the nine methodological guidelines selected. RESULTS: It was found that 29 studies satisfied the inclusion criteria. The societal perspective was taken in 13 out of the 29 studies (45%), an adequate time period of analysis was chosen in 21 (72%), effectiveness was explicitly differentiated from efficacy in 17 (59%), an incremental analysis was performed in 23 (79%), costs, benefits and health gains were discounted in 24 (83%), effectiveness was expressed in LYGs or QALYs in 16 (55%), reference prices were used in 8 (28%), subgroup analysis was presented in 13 (45%) and sensitivity analysis was included in 26 (90%). CONCLUSIONS: In this review we found that the adherence of studies to some of the Dutch guidelines for pharmacoeconomic studies is fair. However, major improvements are required with respect to the adoption of the societal perspective, presentation of adequate subgroup analyses and application of reference prices.