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.

Multinational evidence of the applicability and robustness of discrete choice modeling for deriving EQ-5D-5L health-state values.

AIMS: To investigate the feasibility of discrete choice experiments for valuing EQ-5D-5L states using computer-based data collection, the consistency of the estimated regression coefficients produced after modeling the preference data, and to examine the similarity of the values derived across countries. METHODS: Data were collected in Canada, England, The Netherlands, and the United States (US). Interactive software was developed to standardize the format of the choice tasks across countries, except for face-to-face interviewing in England. The choice task required respondents to choose between 2 suboptimal health states. A Bayesian design was used to generate 200 pairs of states that were randomly grouped into 20 blocks. Each respondent completed 1 block of 10 pairs. A main-effects probit model was used to estimate regression coefficients and to derive values. RESULTS: Approximately 400 respondents participated from each country. The mean time to perform 1 choice task was between 29.2 (US) and 45.2 (England) seconds. All regression coefficients were statistically significant, except level 2 for Usual Activities in The Netherlands (P=0.51). Predictions for the complete set of 3125 EQ-5D-5L health states were similar for the 4 countries. Intraclass correlation coefficients between the countries were high: from 0.80 (England vs. US) through 0.98 (Canada vs. US) CONCLUSIONS: Derivation of value sets from the general population using computer-based choice tasks for the EQ-5D-5L is feasible. Parameter estimates were generally consistent and logical, and health-state values were similar across the 4 countries.

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

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Dose-related effect of methylphenidate on stopping and changing in children with attention-deficit/hyperactivity disorder.

PURPOSE: The effect of methylphenidate (MPH) on inhibitory control as assessed by the stop task in children with attention-deficit/hyperactivity disorder (ADHD) could be influenced by task difficulty and may be mediated by attention. SUBJECTS AND METHODS: Fifteen children with ADHD performed the stop and the change task after placebo, 0.5 and 1.0 mg/kg MPH in a within-subject design. RESULTS: Linear-trend analysis showed a similar effect of MPH in both tasks and a stronger effect for inhibitory control than for attention. Furthermore, a correlation was found between blood serum metabolites of norepinephrine and dopamine for attentional measures and inhibitory control measures, respectively. DISCUSSION AND CONCLUSION: In children with ADHD MPH could act primarily on inhibitory control, and is not influenced by task difficulty. Also, attention and inhibitory control could have differential pharmacological profiles.

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).

The bilirubin albumin ratio in the management of hyperbilirubinemia in preterm infants to improve neurodevelopmental outcome: a randomized controlled trial--BARTrial.

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN74465643.

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.