Cost-effectiveness of proactive health support-telephone-based self-management support compared with standard care for persons at risk of hospital admission.

BACKGROUND: A small share of patients account for a large proportion of costs to the healthcare system in Denmark as in many Western countries. A telephone-based self-management support, proactive health support (PaHS), was suggested for prevention of hospitalisations for persons at risk of hospital admission. These persons have chronic diseases, unplanned hospitalisations and age ≥ 65 years. However, evidence is limited on whether this type of intervention is cost-effective. AIM: The aim of this study was to assess the incremental cost-utility ratio (ICER) of PaHS, compared with standard care. METHODS: The economic evaluation was nested within a randomised controlled trial, and was based on a health system perspective, with follow-up and time horizon of 12 months. We measured incremental costs per quality-adjusted life years (QALY) gained. Total average costs per patient included PaHS programme costs, and costs in hospitals, primary care and municipalities. We analysed differences by generalised linear models with Gamma distribution for costs and mixed models for QALY. RESULTS: We analysed data on 6,139 patients, where 3,041 received PaHS and 3,098 received usual care. We found no difference in healthcare costs, and programme costs were on average €1,762 per patient, providing incremental costs of €2,075. Incremental effects on QALY were 0.007, resulting in an ICER of €296,389 per QALY gained. CONCLUSION: We found no evidence of PaHS being cost-effective in this study, but the results will be used to identify new ways to organise similar interventions and identify patients with the objective to reduce health system costs per patient.

Self-Reported Health as Predictor of Allostatic Load and All-Cause Mortality: Findings From the Lolland-Falster Health Study.

Objectives: The aim was to determine the association between self-reported health (SRH), allostatic load (AL) and mortality. Methods: Data derived from the Lolland-Falster Health Study undertaken in Denmark from 2016-2020 (n = 14,104). Median follow-up time for death was 4.6 years where 456 participants died. SRH was assessed with a single question and AL by an index of ten biomarkers. Multinomial regression analysis were used to examine the association between SRH and AL, and Cox regression to explore the association between SRH, AL and mortality. Results: The risk of high AL increased by decreasing level of SRH. The ratio of relative risk (RRR) of having medium vs. low AL was 1.58 (1.11-2.23) in women reporting poor/very poor SRH as compared with very good SRH. For men it was 1.84 (1.20-2.81). For high vs. low AL, the RRR was 2.43 (1.66-3.56) in women and 2.96 (1.87-4.70) in men. The hazard ratio (HR) for all-cause mortality increased by decreasing SRH. For poor/very poor vs. very good SRH, the HR was 6.31 (2.84-13.99) in women and 3.92 (2.12-7.25) in men. Conclusion: Single-item SRH was able to predict risk of high AL and all-cause mortality.

Correlation between allostatic load index and cumulative mortality: a register-based study of Danish municipalities.

OBJECTIVES: The aim of this study was to examine population-based allostatic load (AL) indices as an indicator of community health across 14 municipalities in Denmark. DESIGN: Register-based study. SETTING: Data derived from: the Lolland-Falster Health Study, the Copenhagen General Population Study and the Danish General Suburban Population Study. Nine biomarkers (systolic blood pressure, diastolic blood pressure, pulse rate, total serum cholesterol, high-density lipoprotein cholesterol, waist-to-hip ratio, triglycerides, C-reactive protein and serum albumin) were divided into high-risk and low-risk values based on clinically accepted criteria, and the AL index was defined as the average between the nine values. All-cause mortality data were obtained from Statistics Denmark. PARTICIPANTS: We examined a total of 106 808 individuals aged 40-79 years. PRIMARY OUTCOME MEASURE: Linear regression models were performed to investigate the association between mean AL index and cumulative mortality risk. RESULTS: Mean AL index was higher in men (range 2.3-3.3) than in women (range 1.7-2.6). We found AL index to be strongly correlated with the cumulative mortality rate, correlation coefficient of 0.82. A unit increase in mean AL index corresponded to an increase in the cumulative mortality rate of 19% (95% CI 13% to 25%) for men, and 16% (95% CI 8% to 23%) for women but this difference was not statistically significant. The overall mean increase in cumulative mortality rate for both men and women was 17% (95% CI 14% to 20%). CONCLUSIONS: Our findings indicate the population-based AL index to be a strong indicator of community health, and suggest identification of targets for reducing AL.

Nurses' perspectives on challenges and facilitators when implementing a self-management support intervention as an everyday healthcare practice: A qualitative study.

AIM: To explore registered nurses' perspectives on challenges and facilitators to implementing a telephone-based self-management support (SMS) intervention (Proactive Health Support) as an everyday healthcare practice, during the early stages of implementation. DESIGN: Data were collected using a qualitative research design involving focus-group interviews and participant observations. METHODS: We conducted participant observation following nine nurses and four focus group interviews with 14 nurses. Data were analysed using thematic analyses. RESULTS: Proactive Health Support was implemented in units organized independently of the existing organizational units within healthcare services. This independent organization, along with the intervention's generic (non-disease specific) design, empowered nurses to become autonomous practitioners capable of prioritizing the operationalization of SMS as an everyday healthcare practice. However, unlearning already embedded medical practices and establishing new nursing roles necessary to accommodate the intervention in practice was experienced a challenge. Education and supervision were identified as valuable tools for successful implementation. CONCLUSION: Our study highlights the significance of organizational context and autonomy in successful SMS implementation. Balancing external factors like organizational context, priority and time is vital, but navigating the internal shift in professional practice is equally crucial. Role transition processes can constitute challenges demanding accommodation. IMPLICATIONS FOR THE PROFESSION: From a nursing perspective, this study highlights that practising SMS requires substantial training and education. Generic SMS interventions can introduce higher levels of contingency due to their versatile nature. Thus, equipping nurses with competencies that enable them to navigate this unpredictability flexibly is crucial. IMPACT: Policymakers and administrators should allocate resources and support implementation processes in ways that accommodate both internal and external conditions to facilitate nurses in delivering effective SMS. REPORTING METHOD: This study adheres to the SRQR guideline. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Who benefits from self-management support? Results from a randomized controlled trial.

Background: Self-management support models adapted to accommodate the needs of each patient are complex interventions that should be evaluated for intervention mechanisms. In a national randomized controlled trial (RCT), we evaluated the efficacy of telephone-based self-management support that demonstrated improved health-related quality of life (HRQoL), no reduction in hospital admissions, and an unexpected increase in primary healthcare services. Objective: The objective of this study is to identify RCT impact mechanisms and explore which participants could benefit the most from the PaHS intervention. Methods: This study evaluates intervention mechanisms through interaction analyses of predefined intervention moderators (sex, age, education, chronic disease, risk of hospital admissions, and coping) and post-hoc intervention mediators (contacts in primary care and anxiety medication). The one co-primary outcome HRQoL was assessed with SF26v2 and analyzed with generalized linear mixed models and the other co-primary hospital admissions was analyzed with poisson regression. Results: PaHS interacted with diabetes, multimorbidity, coping, and anxiety medication on the outcome hospital admissions. PaHS led to a significant reduction in hospital admissions in participants with diabetes or multimorbidity and an increase in hospital admissions in participants with higher baseline coping and participants using anxiety medication. The interaction analyses revealed significant intervention mediation in the outcome HRQoL by sex and diabetes. Conclusions: Participants with diabetes, multimorbidity, and women could benefit the most from telephone-based self-management support, but the intervention involves the risk of over-treatment.

A cross-sectional study of the association between family conflicts and children's health: Lolland-Falster Health Study.

BACKGROUND: Few family interaction processes are more detrimental to children's health than family conflicts. Conflictual relationships in childhood predict a host of adverse health outcomes across the life course. The current study examines associations between household conflicts and the health of children aged 6-12 years and explores to which extent this may vary by socioeconomic status (SES) and multimorbidity (MM) in the household. METHODS: Cross-sectional study using questionnaire data gathered between 2016 and 2020 as part of the Lolland-Falster Health Study (LOFUS) combined with routine register data on health care use and socio-demography from the Danish nationwide administrative databases. The study sample consisted of 1065 children 6-12 years old, who answered LOFUS4 or LOFUS11, from 777 households for which at least one adult answered LOFUS18. Main outcome was children's health complaints, defined as headache, abdominal pain, back pain, and sleep difficulties. Covariates included MM, SES, and conflicts, all three measured at household level. Multivariable logistic regression models were used. RESULTS: Conflicts were negatively associated with children's health. This was most pronounced for general conflicts in the household, with increased complaints of abdominal pain, back pain, and sleep difficulties. The associations varied when we stratified the households according to MM and SES. Significant associations were found within households without MM for abdominal pain, and within households with MM and low SES, and without MM and with high SES for sleep difficulties. While the higher level of abdominal pain for the above indicated households were found for both internal and external conflicts in the household, the higher level in sleep difficulties was mostly driven by internal conflicts. CONCLUSION: Children reporting frequent health complaints have a higher future health care use compared with children without such complaints. Our results indicate that growing up in a household with a high conflict level might be a predisposing factor.

Proactive Health Support: a randomised controlled trial of telephone-based self-management support for persons at risk of hospital admission.

BACKGROUND: Persons with frequent hospital admissions have a disease burden that may exceed their self-management skills. The evidence base of telephone-based interventions to support self-management is poor with mixed results. The aim of this study is to evaluate the effect of Proactive Health Support (PaHS): telephone-based self-management support for persons with risk of hospitalizations. METHODS: This study is a national randomised controlled trial of PaHS versus usual universal tax-funded healthcare. Participants were persons at risk of emergency hospital admissions. The intervention began with a physical start-up session followed by telephone sessions of self-management support. The two co-primary outcomes were Health-Related Quality of Life (HRQoL) (Mental Health Component Summary Score of SF36v2) analysed with mixed models and hospital admissions analysed with Poisson regression at 6 months. Secondary outcomes were at 3- and 12-month follow-up and disease subgroup analyses. RESULTS: During the study period, 6,402 persons were randomised (3,190 intervention, 3,212 control). HRQoL was significantly improved at 6 months (Est. 1.4992, P = <0.0001) and at 3 and 12 months on all 10 scales. There was no overall effect on hospital admissions at 6 months with an adjusted estimate of 0.0074 (P = 0.8691). Persons with diabetes had significant improvement of HRQoL and reduced hospital admissions. CONCLUSIONS: The PaHS intervention improved HRQoL for all participants and reduced hospital admissions for persons with diabetes only.

Lung function in Lolland-Falster Health Study (LOFUS).

BACKGROUND: COPD prevalence in Denmark is estimated at 18% based on data from urban populations. However, studies suggest that using the clinical cut-off for airway obstruction in population studies may overestimate prevalence. The present study aims to compare estimated prevalence of airway obstruction using different cut-offs and to present lung function data from the Lolland-Falster Health Study, set in a rural-provincial area. METHODS: Descriptive analysis of participant characteristics and self-reported respiratory disease and of spirometry results in the total population and in subgroups defined by these characteristics. Airway obstruction was assessed using previously published Danish reference values and defined according to either FEV1 /FVC below lower limit of normal (LLN) 5% (as in clinical diagnosis) or 2.5% (suggested for population studies), or as FEV1 /FVC < 70%. RESULTS: Using either FEV1 /FVC < 70% or LLN 5% cut-off, 19.0% of LOFUS participants aged 35 years or older had spirometry, suggesting airway obstruction. By the LLN 2.5% criterion, the proportion was considerably lower, 12.2%. The prevalence of airway obstruction was higher among current smokers, in participants with short education or reporting low leisure-time physical activity and in those with known respiratory disease. Approximately 40% of participants reporting known respiratory disease had normal spirometry, and 8.7% without known respiratory disease had airway obstruction. CONCLUSION: Prevalence of airway obstruction in this rural population was comparable to previous estimates from urban Danish population studies. The choice of cut-off impacts the estimated prevalence, and using the FEV1 /FVC cut-off may overestimate prevalence. However, many participants with known respiratory disease had normal spirometry in this health study.

Allostatic load as predictor of mortality: a cohort study from Lolland-Falster, Denmark.

OBJECTIVES: The purposes of the present study were to determine the association between (1) 10 individual biomarkers and all-cause mortality; and between (2) allostatic load (AL), across three physiological systems (cardiovascular, inflammatory, metabolic) and all-cause mortality. DESIGN: Prospective cohort study. SETTING: We used data from the Lolland-Falster Health Study undertaken in Denmark in 2016-2020 and used data on systolic blood pressure (SBP) and diastolic blood pressure (DBP), pulse rate (PR), waist-hip ratio (WHR) and levels of low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), triglycerides, glycated haemoglobin A1c (HbA1c), C-reactive protein (CRP) and serum albumin. All biomarkers were divided into quartiles with high-risk values defined as those in the highest (PR, WHR, triglycerides, HbA1c, CRP) or lowest (HDL-c, albumin) quartile, or a combination hereof (LDL-c, SBP, DBP). The 10 biomarkers were combined into a summary measure of AL index. Participants were followed-up for death for an average of 2.6 years. PARTICIPANTS: We examined a total of 13 725 individuals aged 18+ years. PRIMARY OUTCOME MEASURE: Cox proportional hazard regression (HR) analysis were performed to examine the association between AL index and mortality in men and women. RESULTS: All-cause mortality increased with increasing AL index. With low AL index as reference, the HR was 1.33 (95% CI: 0.89 to 1.98) for mid AL, and HR 2.37 (95% CI: 1.58 to 3.54) for high AL. CONCLUSIONS: Elevated physiological burden measured by mid and high AL index was associated with a steeper increase of mortality than individual biomarkers.

Predicting Individual Risk of Emergency Hospital Admissions - A Retrospective Validation Study.

PURPOSE: A high number of hospital admissions may indicate poor general health and less than optimal health care across sectors. To prevent hospital admissions, previous studies have focused on predicting readmissions relating to a defined index admission and specific condition, whereas generic models suited for community-dwelling persons are lacking. The aim of this study was to validate a generic model that predicted risk of emergency hospital admission within the following three months and to investigate regional variation. MATERIALS AND METHODS: This study is an observational register-based validation study of a prediction model. The prediction model was based on a population of frail elderly, persons with non-communicable diseases, and persons with three emergency hospital admissions using information about diagnoses and hospital contacts. The prediction model consisted of two stages. In the first stage, covariate associations to admissions are estimated from observed data in one year. In the second stage, admissions are predicted in the coming three months based on observed estimations from the first stage. The validity of the model was calculated by comparing predicted and observed admissions from August 1st to October 31st, 2016. RESULTS: The study included 112,026 persons. In nationwide data, area under the curve (AUC) was 0.7742 (95% CI 0.7698-0.7786), and the positive predictive value was 52% for the 99th percentile (the top 1%). AUC varied between regions from 0.6914 in Southern Denmark (95% CI 0.6779-0.7049) to 0.8224 (95% CI 0.8064-0.8384) in North Denmark. AUC was higher with nationwide data compared to regional. CONCLUSION: The model performed satisfactorily in predicting individual risk of emergency hospital admission.

Reference intervals for 12 clinical laboratory tests in a Danish population: The Lolland-Falster Health Study.

Reference intervals (RIs), developed as part of the Nordic Reference Interval Project 2000 (NORIP) are widely used in most European laboratories. We aimed to examine the validity of the NORIP RIs by establishing RIs for 12 frequently used laboratory tests based on data from a local Danish population and compare these local RIs with the NORIP RIs. Using an a posteriori direct sampling approach, blood sample data were assessed from 11,138 participants aged 18+ years in the Lolland-Falster Health Study (LOFUS), of whom 2154 turned out to meet criteria for being healthy for inclusion in establishing RIs according to the NORIP methodology. The 2.5th and 97.5th percentiles were calculated for alanine aminotransferase (ALAT), albumin, alkaline phosphatase, bilirubin, creatinine, hemoglobin, high-density lipoprotein cholesterol, iron, low-density lipoprotein cholesterol, thrombocytes, total cholesterol, and triglycerides. When comparing our estimates with the NORIP, the lower reference limits (RLs) for bilirubin and iron were lower, and higher for ALAT, thrombocytes and triglycerides. Upper RLs were lower for albumin (males and females ≥70 years), bilirubin and iron, but higher for alkaline phosphatase, triglycerides and for creatinine in men. In LOFUS, approximately 20% of the participants were healthy and qualified for inclusion in the establishment of RIs. Several of the local RIs differed from the NORIP RIs.

Burden of prediabetes, undiagnosed, and poorly or potentially sub-controlled diabetes: Lolland-Falster health study.

BACKGROUND: This study aimed to investigate prevalence and risk factors for prediabetes, undiagnosed diabetes mellitus, poorly and potentially sub-controlled diabetes in a rural-provincial general adult population in Denmark. METHODS: Using cross-sectional data from the Lolland-Falster Health Study, we examined a total of 10,895 individuals aged 20 years and above. RESULTS: Prevalence of prediabetes was 5.8% (men: 6.1%; women: 5.5%); of undiagnosed diabetes 0.8% (men: 1.0%; women: 0.5%); of poorly controlled diabetes 1.2% (men: 1.5%; women: 0.8%); and of potentially sub-controlled diabetes 2% (men: 3.0%; women: 1.3%). In total, 9.8% of all participants had a diabetes-related condition in need of intervention; men at a higher risk than women; RR 1.41 (95% CI 1.26-1.58); person aged + 60 years more than younger; RR 2.66 (95% CI 2.34-3.01); obese more than normal weight person, RR 4.51 (95% CI 3.79-5.38); smokers more than non-smokers, RR 1.38 (95% CI 1.19-1.62); persons with self-reported poor health perception more than those with good, RR 2.59 (95% CI 2.13-3.15); low leisure time physical activity more than those with high, RR 2.64 (95% CI 2.17-3.22); and persons with self-reported hypertension more than those without, RR 3.28 (95% CI 2.93-3.68). CONCLUSIONS: In the Lolland-Falster Health Study, nearly 10% of participants had prediabetes, undiagnosed diabetes, poorly controlled, or potentially sub-controlled diabetes. The risk of these conditions was more than doubled in persons with self-reported poor health perception, self-reported hypertension, low leisure time physical activity, or measured obesity, and a large proportion of people with diabetes-related conditions in need of intervention can therefore be identified relatively easily.

The national implementation of 'Proactive Health Support' in Denmark since 2017: Expectations and challenges for the telephone-based self-management program.

In Denmark, as in many other Western countries, a small group of people are major hospital users and account for a large proportion of health care spending. Proactive Health Support (PaHS) is the first national Danish program that aims to reduce health care consumption targeting people at risk of becoming major users of health services. PaHS was part of the government's The sooner-the better national health policy, which includes a focus on policy programs targeting the weakest and most complex chronic patients at risk of high health care consumption. PaHS is a telephone-based self-management support program that uses a prediction model to identify people at high risk of acute hospital admissions. Reducing preventable hospital admissions and enhancing quality of life are central policy goals. The Danish policy was inspired by a Swedish policy program, and PaHS has been implemented based on policy transfer with political expectations that the Swedish results can be replicated in Denmark. The effects of PaHS are currently under study, and time will show whether expectations can be met. This paper discusses institutional conditions and expectations related to replicating a policy program and its outcomes. In addition, it highlights implementation issues that may affect the success of the policy program.

Proactive health support (PaHS) - telephone-based self-management support for persons at risk of hospital admission: Study protocol for a randomized controlled trial.

BACKGROUND: A small proportion of patients account for most of the healthcare costs. Previous studies of supportive interventions have several methodological limitations and results are mixed. This article describes the protocol for Proactive Health Support: a national randomized controlled trial of telephone-based self-management support (ClinicalTrials.gov, NCT03628469). The main aim of the intervention is to reduce hospital admissions and improve quality of life at six months. METHODS: A sample size of 4400 is needed and individuals with the highest risk of hospital admission in Denmark are invited by electronic communication and telephone to participate in a 1:1 randomized controlled trial. The intervention group receives one face-to-face start-up session followed by telephone sessions about individual goals regarding participants' knowledge, coping and need of healthcare. Quality of life was assessed with the mental health composite score of the SF-36v2 questionnaire. Primary analyses are done using the intention-to-treat principle. DISCUSSION: The trial has been approved by The Regional Committee on Health Research Ethics (SJ-677). Intervention nurses do not assume clinical responsibility for the participants and the intervention is an addition to the general healthcare services. The intervention is complex due to challenging skills and behaviors required by nurses, individual tailoring of the intervention, and interacting intervention components. The study therefore includes process evaluation. The research program comprises: 1. Development initiation, 2. Intervention effect, 3. Cost-effectiveness, 4. Organizational implementation, and 5. Participants' experiences. Inclusion to the trial began April 9th, 2018, was completed July 1st, 2019 and follow-up will be completed February 1st, 2020.

Questionnaire development for the Lolland-Falster Health Study, Denmark: an iterative and incremental process.

In composing multi-thematic questionnaires for the Lolland-Falster Health Study (LOFUS), we faced a range of challenges, for which we found limited guidance in the literature. LOFUS is a household-based population study covering multiple medical and social research areas and targeting the mixed rural-provincial population of 103,000 persons on the Danish islands Lolland and Falster. Households were randomly selected for invitation. In this paper, we describe and discuss challenges in developing the questionnaires related to stakeholders, content of the questionnaire, and the process itself. The development process was characterised by loops of learning and can be described as an iterative and incremental process. We propose recommendations to researchers and administrators involved in similar development processes, including awareness of the non-linearity and complexity of the process, a need for negotiations and navigation among multiple stakeholders, and acknowledgement of pragmatism as an inherent part of decisions made in the process.

Lolland-Falster Health Study: Study protocol for a household-based prospective cohort study.

Introduction: Lolland-Falster consists of two islands in the southern part of Denmark where income is lower and life expectancy is shorter than in the general Danish population. It is a mixed rural-provincial area with approximately 100,000 inhabitants. The Lolland-Falster Health Study was initiated to gain knowledge on the determinants of health in this disadvantaged area. Methods: The study is a household-based prospective cohort study including people of all ages. The entire household of randomly selected inhabitants is allocated either to an invited group or to an uninvited, non-contacted control group. The data collection encompasses questionnaires, physical examination and biological samples, i.e. blood and urine for same-day analysis and biobank storage, and saliva and faeces also for biobank storage. The civil registration number links collected data for each individual, family and household, with information in Danish registers. The data collection started in February 2016 and is estimated to end by 2019 after the enrolment of 20,000 people. Analysis: A number of in-depth sub-studies are planned. Emphasis will be given to analysis of intra- and inter-family variations in health determinants, genetics, lifestyle and health status. Ethics: Region Zealand's Ethical Committee on Health Research (SJ-421) and the Danish Data Protection Agency (REG-24-2015) approved the study. Trial registration: Clinicaltrials.gov (NCT02482896). Strength and limitations of this study: The strength of this study is that Lolland-Falster Health Study is a useful scientific resource for investigating cross-sectional difference and time trends within and between individuals, families and households. LOFUS adds diversity to the previously collected Danish population studies in urbanized areas. The limitation is that data collection is expensive. Conclusions: LOFUS will contribute to the knowledge on health in disadvantaged, rural-provincial areas.

The Effect of High Dose Cholecalciferol on Arterial Stiffness and Peripheral and Central Blood Pressure in Healthy Humans: A Randomized Controlled Trial.

BACKGROUND: Low levels of serum 25-hydroxy vitamin D are associated with increased arterial stiffness and hypertension. Supplementation with vitamin D precursors has been proposed as a treatment option for these conditions. We examined the effect of oral cholecalciferol on arterial stiffness and blood pressure in healthy normotensive adults. METHODS: 40 healthy adults were randomised in this double-blinded study to either oral cholecalciferol 3000 IU/day or matching placebo and were followed for 16 weeks to examine any effects on pulse wave velocity (PWV), augmentation index (AIx), peripheral and central blood pressure and 24-hour ambulatory blood pressure. RESULTS: 22 subjects in the cholecalciferol arm and 18 subjects in the placebo arm completed the 16 weeks of follow-up. There was no difference in changes in PWV, AIx corrected for heart rate or central or peripheral blood pressure between the two groups. There was no correlation between serum 25-hydroxy vitamin D and any of these parameters. CONCLUSIONS: Oral cholecalciferol 3000 IU/day does not affect arterial stiffness or blood pressure after 16 weeks of treatment in healthy normotensive adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT00952562.

[Thiazide diuretics in the treatment of hypertensive patients]. / Anvendelse af thiaziddiuretika i hypertensions-behandlingen--en gennemgang af et Cochranereview.

This Cochrane review had the objectives to determine the dose-related decrease in blood pressure due to thiazide diuretics compared with placebo control in the treatment of hypertensive patients. Hydrochlorothiazide has a dose-related blood pressure-lowering effect over the dose range 6.25, 12.5, 25 and 50 mg/day of 4/2, 6/3, 8/3 and 11/5 mmHg, respectively. This exceeds the mean 3 mmHg reduction achieved by angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers as shown in other Cochrane reviews, which have compared these antihypertensive drugs with placebo having used similar inclusion/exclusion criteria.

The influence of vitamin D analogs on calcification modulators, N-terminal pro-B-type natriuretic peptide and inflammatory markers in hemodialysis patients: a randomized crossover study.

BACKGROUND: The risk of cardiovascular disease is tremendously high in dialysis patients. Dialysis patients treated with vitamin D analogs show decreased cardiovascular morbidity and mortality compared with untreated patients. We examined the influence of two common vitamin D analogs, alfacalcidol and paricalcitol, on important cardiovascular biomarkers in hemodialysis patients. Anti-inflammatory effects and the influence on regulators of vascular calcification as well as markers of heart failure were examined. METHODS: In 57 chronic hemodialysis patients enrolled in a randomized crossover trial comparing paricalcitol and alfacalcidol, we examined the changes in osteoprotegerin, fetuin-A, NT-proBNP, hs-Crp, IL-6 and TNF-α, during 16 weeks of treatment. RESULTS: NT-proBNP and osteoprotegerin increased comparably in the paricalcitol and alfacalcidol-treated groups. Fetuin-A increased significantly in the alfacalcidol-treated group compared with the paricalcitol-treated group (difference 32.84 µmol/l (95% C.I.; range 0.21-67.47)) during the first treatment period. No difference was found between the groups during the second treatment period, and IL-6, TNF-α and hs-Crp were unchanged in both treatment groups. CONCLUSIONS: Paricalcitol and alfacalcidol modulate regulators of vascular calcification. Alfacalcidol may increase the level of the calcification inhibitor fetuin-A. We did not find any anti-inflammatory effect or difference in changes of NT-proBNP. TRIAL REGISTRY: ClinicalTrials.gov NCT00469599 May 3 2007.