Effect of absolute blood volume measurement-guided fluid management on the incidence of intradialytic hypotension-associated events: a randomised controlled trial.

Background: Ultrafiltration to target weight during haemodialysis is complicated by intradialytic hypotension-associated adverse events (IHAAEs) in 10-30% of dialysis treatments. IHAAEs are caused by critical reductions in absolute blood volume (ABV), due to the interaction of ultrafiltration, refill and compensatory mechanisms. Non-randomised studies have suggested that ABV-guided treatment, using an indicator dilution technique employing the blood volume monitor on the dialysis machine, could reduce the incidence of IHAAEs. Methods: We performed an open-label randomised controlled trial. Patients were randomly assigned to adjustment of target weight guided by ABV measurements or standard care. The primary outcome was the change in the incidence of IHAAEs from baseline, defined as the percentage of treatment episodes in a 4-week period where the patient had a systolic blood pressure <90 mmHg or symptoms of impending hypotension. ABV measurements were compared with anthropomorphometric estimation and the gold standard using isotope dilution. Results: A total of 56 patients were randomised, of whom 29 were allocated to ABV-guided treatment and 27 to standard care. Overall baseline incidence of IHAAEs was 26.0%. ABV-guided treatment significantly reduced the incidence of IHAAEs compared with standard care, with a mean change from baseline of -9.6% [95% confidence interval (CI) -17.3 to -1.8) versus 2.4% (95% CI -2.3-7.2). The adjusted difference between the groups was 10.5% (95% CI 1.3-19.8; P = .026). ABV measurement had moderate agreement with other methods to estimate blood volume. The sensitivity for the previously suggested threshold of a post-dialysis normalised blood volume of 65 ml/kg was observed to be 74% in this study. Conclusions: ABV-guided volume management significantly reduced IHAAEs compared with standard care. The clinical relevance of the previously suggested threshold of 65 ml/kg cannot be firmly concluded on the basis of our results. If confirmed in a larger trial, this intervention could potentially change dialysis practice and impact patient care in a clinically meaningful way.

Assessment of human fetal cardiac autonomic nervous system development using color tissue Doppler imaging.

OBJECTIVES: Functional development of the fetal cardiac autonomic nervous system (cANS) plays a key role in fetal maturation and can be assessed through fetal heart rate variability (fHRV)-analysis, with each HRV parameter representing different aspects of cANS activity. Current available techniques, however, are unable to assess the fHRV parameters accurately throughout the whole pregnancy. This study aims to test the feasibility of color tissue Doppler imaging (cTDI) as a new ultrasound technique for HRV analysis. Secondly, we explored time trends of fHRV parameters using this technique. METHODS: 18 healthy singleton fetuses were examined sequentially every 8 weeks from 10 weeks GA onwards. From each examination, 3 cTDI recordings of the four-chamber view of 10 seconds were retrieved to determine accurate beat-to-beat intervals. The fHRV parameters SDNN, RMSSD, SDNN/RMSSD, and pNN10, each representing different functional aspects of the cANS, were measured, and time trends during pregnancy were explored using spline functions within a linear mixed-effects model. RESULTS: In total, 77% (95% Cl 66-87%) of examinations were feasible for fHRV analysis from the first trimester onwards, which is a great improvement compared to other techniques. The technique is able to determine different maturation rates of the fHRV parameters, showing that cANS function, presumably parasympathetic activity, establishes around 20 weeks GA and matures rapidly until 30 weeks GA. CONCLUSIONS: This is the first study able to assess cANS function through fHRV analysis from the first trimester onwards. The use of cTDI to determine beat-to-beat intervals seems feasible in just 3 clips of 10 seconds, which holds promise for future clinical use in assessing fetal well-being.

Deprescribing preventive cardiovascular medication in patients with predicted low cardiovascular disease risk in general practice - the ECSTATIC study: a cluster randomised non-inferiority trial.

BACKGROUND: The use of cardiovascular medication for the primary prevention of cardiovascular disease (CVD) is potentially inappropriate when potential risks outweigh the potential benefits. It is unknown whether deprescribing preventive cardiovascular medication in patients without a strict indication for such medication is safe and cost-effective in general practice. METHODS: In this pragmatic cluster randomised controlled non-inferiority trial, we recruited 46 general practices in the Netherlands. Patients aged 40-70 years who were using antihypertensive and/or lipid-lowering drugs without CVD and with low risk of future CVD were followed for 2 years. The intervention was an attempt to deprescribe preventive cardiovascular medication. The primary outcome was the difference in the increase in predicted (10-year) CVD risk in the per-protocol (PP) population with a non-inferiority margin of 2.5 percentage points. An economic evaluation was performed in the intention-to-treat (ITT) population. We used multilevel (generalised) linear regression with multiple imputation of missing data. RESULTS: Of 1067 participants recruited between 7 November 2012 and 18 February 2014, 72% were female. Overall, their mean age was 55 years and their mean predicted CVD risk at baseline was 5%. Of 492 participants in the ITT intervention group, 319 (65%) quit the medication (PP intervention group); 135 (27%) of those participants were still not taking medication after 2 years. The predicted CVD risk increased by 2.0 percentage points in the PP intervention group compared to 1.9 percentage points in the usual care group. The difference of 0.1 (95% CI -0.3 to 0.6) fell within the non-inferiority margin. After 2 years, compared to the usual care group, for the PP intervention group, systolic blood pressure was 6 mmHg higher, diastolic blood pressure was 4 mmHg higher and total cholesterol and low-density lipoprotein-cholesterol levels were both 7 mg/dl higher (all P < 0.05). Cost and quality-adjusted life years did not differ between the groups. CONCLUSIONS: The results of the ECSTATIC study show that an attempt to deprescribe preventive cardiovascular medication in low-CVD-risk patients is safe in the short term when blood pressure and cholesterol levels are monitored after stopping. An attempt to deprescribe medication can be considered, taking patient preferences into consideration. TRIAL REGISTRATION: This study was registered with Dutch trial register on 20 June 2012 ( NTR3493 ).

[Identification of seniors at risk--primary care: a validated questionnaire predicting functional decline]. / Een gevalideerd screeningsinstrument voorspelt functieverlies bij thuiswonende ouderen: de Identification of Seniors at Risk--Primary Care (ISAR-PC).

OBJECTIVES: To modify and validate in primary healthcare the Identification of Seniors At Risk (ISAR) screening questionnaire to identify older persons at increased risk of functional decline and to compare this strategy with risk stratification by age alone. STUDY DESIGN AND SETTING: Prospective development (n=790) and validation cohorts (n=2,573) of community-dwelling persons aged ≥70 years. Functional decline at 12 months was defined as an increase of at least one point on the modified Katz-activities of daily living index score compared with baseline or death. RESULTS: Three items were independently associated with functional decline: age (odds ratio [OR] 1.06 per year; 95% confidence interval [CI] 1.02, 1.10) dependence in instrumental activities of daily living (OR: 2.17; 95% CI: 1.46, 3.22), and impaired memory (OR: 2.22; 95% CI: 1.41, 3.51). The area under the receiver operating characteristics curve (AUC) range of the ISAR-primary care model was 0.67-0.70 and 40.6% was identified at increased risk. Validation yielded an AUC range of 0.63-0.64. Age≥75 years alone yielded an AUC range of 0.56-0.57 and identified 65.0% at increased risk in the validation cohort. CONCLUSION: Although the ISAR-Primary Care (ISAR-PC) has moderate predictive value, application of the ISAR-PC is more efficient than selection based on age alone in identifying persons at increased risk of functional decline. This paper is a translated and adjusted version based on a publication in Journal of Clinical Epidemiology, 67 (2014) 1121-1130.