Discontinuing Inappropriate Medication in Nursing Home Residents (DIM-NHR Study):Protocol of a cluster randomised controlled trial

INTRODUCTION: Nursing home residents often have a high number of comorbidities resulting in polypharmacy. Inappropriate prescribing is therefore likely to occur, which in turn is expected to worsen cognitive impairment, to increase the fall risk and to decrease residents' quality of life. The objective of the 'Discontinuing Inappropriate Medication in Nursing Home Residents' (DIM-NHR) study is to examine the efficacy and cost-effectiveness of the Multidisciplinary Multistep Medication Review (3MR) that is aimed at optimising prescribing and discontinuing inappropriate medication. METHODS: A cluster randomised controlled trial will be conducted. Elderly care physicians and their wards (clusters) will be randomised. Data will be collected at baseline and 4 months after the 3MR has taken place. Six hundred nursing home residents will be recruited of whom more than half are expected to suffer from dementia. The 3MR will be based on consensus criteria and the relevant literature and will be performed by the patient's elderly care physician in collaboration with a pharmacist. ANALYSIS: Primary outcomes-the difference in proportion of residents who successfully discontinued inappropriate medication between the intervention and control group at follow-up. Secondary outcomes-undertreatment, exposure to anticholinergic and sedative medicines, neuropsychiatric symptoms, cognitive function, falls, hospital admission, quality of life and cost-effectiveness. ETHICS AND DISSEMINATION: Participant burden will be kept at a minimum. The elderly care physician will remain free to adjust medication when symptoms relapse or adverse events occur, rendering serious adverse events highly unlikely. Study findings will be published in peer-reviewed journals and a 3MR toolkit will be developed. TRIAL REGISTRATION NUMBER: This study has been registered at http://www.ClinicalTrials.gov (trial registration number: NCT01876095)

Growth hormone and selective attention: A review

Introduction: The relation between growth hormone (GH) secretion and general cognitive function has been established. General cognitive functioning depends on core functions including selective attention, which have not been addressed specifically in relation to GH. The present review addresses current insights about specific effects of growth hormone deficiency (GHD) on varieties of selective attention, as well as effects of GH suppletion. Materials and methods: Studies investigating relationships between GH status and valid measures of selective or divided attention were reviewed. Results and discussion: There are no indications that GHD is characterized by impaired attribute selection, interference control, or attentional switching. In contrast, a few studies point to a deficit in integrated processing of multiple dimensions, as well as speed of information processing. There is also weak evidence for beneficial effects of GH replacement in the opposite direction in these domains. Conclusions: The function of integrated processing of multiple stimulus dimensions may be based on neural mechanisms in the anterior cingulate cortex and its extensive connections to the hippocampus, the latter being known to be rich in GH receptors. (C) 2010 Elsevier Ltd. All rights reserved

Head-to-head comparison of health-state values derived by a probabilistic choice model and scores on a visual analogue scale

Health states were quantified based on discrete choice (DC) modeling and visual analogue scale (VAS) values using the five-level version of the EQ-5D (EQ-5D-5L). The aim of this study was to determine the extent of the relationship between DC derived values (indirect method) and VAS values (direct method). Data were collected in Canada, the United Kingdom, the Netherlands, and the United States. Respondents were asked to perform paired comparisons between two EQ-5D-5L health states for DC. In total, 400 different EQ-5D-5L states were included. After each DC task, respondents were prompted to score the two states one after another on a VAS. Intraclass correlation coefficients were calculated between DC and VAS values and illuminating graphs were designed. Approximately 400 respondents participated from each country. High similarity [individual intraclass correlation coefficients (ICC) > 0.85] of DC and moderate correspondence of VAS values were observed for the four countries. Cross-country comparison of DC values shows a nonlinear relationship to the VAS values. EQ-5D-5L derived DC and VAS values show a close but nonlinear relationship. Given the obvious biases associated with the VAS, DC methods based on ordinal responses may be a better alternative

Understanding drug preferences, different perspectives

textabstractAims To compare the values regulators attach to different drug effects of oral antidiabetic drugs with those of doctors and patients. Methods We administered a 'discrete choice' survey to regulators, doctors and patients with type 2 diabetes in The Netherlands. Eighteen choice sets comparing two hypothetical oral antidiabetic drugs were constructed with varying drug effects on glycated haemoglobin, cardiovascular risk, bodyweight, duration of gastrointestinal complaints, frequency of hypoglycaemia and risk of bladder cancer. Responders were asked each time which drug they preferred. Results Fifty-two regulators, 175 doctors and 226 patients returned the survey. Multinomial conditional logit analyses showed that cardiovascular risk reduction was valued by regulators positively (odds ratio 1.98, 95% confidence interval 1.11-3.53), whereas drug choices were negatively affected by persistent gastrointestinal problems (odds ratio 0.24, 95% confidence interval 0.14-0.41) and cardiovascular risk increase (odds ratio 0.49, 95% confidence interval 0.27-0.87). Doctors and patients valued these effects in a similar manner to regulators. The values that doctors attached to large changes in glycated haemoglobin and that both doctors and patients attached to hypoglycaemia and weight gain also reached statistical significance. No group's drug choice was affected by a small absolute change in risk of bladder cancer when presented in the context of other drug effects. When comparing the groups, the value attached by regulators to less frequent hypoglycaemic episodes was significantly smaller than by patients (P = 0.044). Conclusions Regulators may value major benefits and risks of drugs for an individual diabetes patient mostly in the same way as doctors and patients, but differences may exist regarding the value of minor or short-term drug effects

Understanding drug preferences, different perspectives

Aims To compare the values regulators attach to different drug effects of oral antidiabetic drugs with those of doctors and patients. Methods We administered a 'discrete choice' survey to regulators, doctors and patients with type 2 diabetes in The Netherlands. Eighteen choice sets comparing two hypothetical oral antidiabetic drugs were constructed with varying drug effects on glycated haemoglobin, cardiovascular risk, bodyweight, duration of gastrointestinal complaints, frequency of hypoglycaemia and risk of bladder cancer. Responders were asked each time which drug they preferred. Results Fifty-two regulators, 175 doctors and 226 patients returned the survey. Multinomial conditional logit analyses showed that cardiovascular risk reduction was valued by regulators positively (odds ratio 1.98, 95% confidence interval 1.11-3.53), whereas drug choices were negatively affected by persistent gastrointestinal problems (odds ratio 0.24, 95% confidence interval 0.14-0.41) and cardiovascular risk increase (odds ratio 0.49, 95% confidence interval 0.27-0.87). Doctors and patients valued these effects in a similar manner to regulators. The values that doctors attached to large changes in glycated haemoglobin and that both doctors and patients attached to hypoglycaemia and weight gain also reached statistical significance. No group's drug choice was affected by a small absolute change in risk of bladder cancer when presented in the context of other drug effects. When comparing the groups, the value attached by regulators to less frequent hypoglycaemic episodes was significantly smaller than by patients (P = 0.044). Conclusions Regulators may value major benefits and risks of drugs for an individual diabetes patient mostly in the same way as doctors and patients, but differences may exist regarding the value of minor or short-term drug effects

The Bilirubin Albumin Ratio in the Management of Hyperbilirubinemia in Preterm Infants to Improve Neurodevelopmental Outcome: A Randomized Controlled Trial - BARTrial

High bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome.In a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death.Composite motor (100 ± 13 vs. 101 ± 12) and cognitive (101 ± 12 vs. 101 ± 11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights ≤ 1000 g and 1.8% versus 5.8% (P = 0.03) and 4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g.The additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome.Controlled-Trials.com ISRCTN74465643

Outcomes at 18 to 24 months.

<p>Plus-minus values are means ± standard deviations. The denominator used to calculate the percentage of infants with a specific outcome was the number of infants randomly assigned to each treatment group for whom that outcome was known at 18 to 24 months. This number was the total number in each group, unless otherwise specified. The motor and cognitive scores were assessed with the BSID III (scores range from 50 to 150, where 150 indicates most advanced development).</p><p>The relative risk of each outcome was calculated for the BA ratio group as compared to the TSB group. In the B/A ratio group the mean (±SD) age at death was 30±16 days and 10±7 days in the TSB group. Severe NDI was a composite motor score of <70, a composite cognitive score of <70, moderate or severe cerebral palsy, severe unilateral or bilateral hearing loss, or unilateral or bilateral blindness. Neurodevelopmental impairment was a composite motor score of <85, a composite cognitive score of <85, any neurological impairment, any visual impairment, or hearing impairment.</p><p>P value#: Outcomes of t-test for continuous variables or Fischer exact test for categorical variables, two-tailed; RR is relative risk with (95% confidence interval). P value ^$: corresponding P value.</p

Baseline characteristics at randomization.

<p>Plus-minus values are means ± standard deviations. The denominator used to calculate the percentages of infants or mothers with a specific characteristic was the number for whom the characteristic was known. This number was the total number in each group, unless otherwise specified. No significant differences were found between the two groups. # Race or ethnicity was reported by patients' parents or guardians or determined by the physician on reviewing the charts.</p