A linear index for predicting joint health-states utilities from single health-states utilities

Direct elicitation of utilities for joint health (JS) states may pose substantial interview burden, while traditional models to predict these utilities from utilities of component single states (SS) are inconsistent with the data. Using individual-level data on utilities for health states associated with prostate cancer, we report the performance of a new model that encompasses three traditional models - additive, multiplicative, and minimum - previously used for predicting utilities for joint health states. Describing utilities in terms of utility losses l(.) relative to prefect health, our final estimated linear index for predicting joint health-state utilities is El(JS)=0.05+0.72 x max l(SS1),l(SS2)+0.33.min x l(SS1),l(SS2)-0.18 x l(SS1) x l(SS2). Based on out-of-sample predictions, this model produces up to 50% reduction in mean-square error compared with traditional models and consistent prediction across different ranges of joint-state utilities, which the traditional models do not. Parameter estimates of the new model proposed here provide direct evidence on the inconsistencies of the traditional models, are grounded in psychological theory by emphasizing the more severe component of a joint health state, and provide a simple linear index to generate consistent predictions of utilities for joint health states. Further validation of this function for joint health states in other clinical scenarios is warranted.     

Cost-Effectiveness of New-Generation Oral Cholera Vaccines: A Multisite Analysis

Objectives:  We evaluated the cost-effectiveness of a low-cost cholera vaccine licensed and used in Vietnam, using recently collected data from four developing countries where cholera is endemic. Our analysis incorporated new findings on vaccine herd protective effects.
Methods:  Using data from Matlab, Bangladesh, Kolkata, India, North Jakarta, Indonesia, and Beira, Mozambique, we calculated the net public cost per disability-adjusted life year avoided for three immunization strategies: 1) school-based vaccination of children 5 to 14 years of age; 2) school-based vaccination of school children plus use of the schools to vaccinate children aged 1 to 4 years; and 3) community-based vaccination of persons aged 1 year and older.
Results:  We determined cost-effectiveness when vaccine herd protection was or was not considered, and compared this with commonly accepted cutoffs of gross domestic product (GDP) per person to classify interventions as cost-effective or very-cost effective. Without including herd protective effects, deployment of this vaccine would be cost-effective only in school-based programs in Kolkata and Beira. In contrast, after considering vaccine herd protection, all three programs were judged very cost-effective in Kolkata and Beira. Because these cost-effectiveness calculations include herd protection, the results are dependent on assumed vaccination coverage rates.
Conclusions:  Ignoring the indirect effects of cholera vaccination has led to underestimation of the cost-effectiveness of vaccination programs with oral cholera vaccines. Once these effects are included, use of the oral killed whole cell vaccine in programs to control endemic cholera meets the per capita GDP criterion in several developing country settings.     

Dynamic aspect of functional recovery after stroke using a multistate model

Pan SL, Lien IN, Yen MF, Lee TK, Chen THH. Dynamic aspect of functional recovery after stroke using a multistate model.

Objective

To estimate time to functional recovery and quantify the effects of significant prognostic factors affecting the dynamic change of 3-state functional outcome after stroke.

Design

Modeling of clinical predictions.

Setting

Referral center.

Participants

One hundred eleven patients with first-time ischemic stroke.

Interventions

Not applicable.

Main Outcome Measure

Serial Barthel Index scores at onset, 2 weeks, and 1, 2, 4, and 6 months poststroke. The severity of disability was classified into 3 functional states: poor functional state (PFS) for Barthel Index scores from 0 to 40, moderate functional state (MFS) for scores from 45 to 80, and good functional state (GFS) for scores greater than 80. A 3-state Markov regression model together with Bayesian acyclic graphic underpinning was used to estimate transition parameters and mean time to functional recovery between states and to predict the probability of functional recovery by using Gibbs sampling technique.

Results

The mean total recovery time was 3.1 months for patients with PFS at baseline and 1.3 months for patients with MFS at baseline. The mean recovery times to different functional states were also estimated. Age predominantly affected the probabilities of MFS to GFS transitions, younger patients had faster transition rates (rate ratio, 4.51; 95% confidence interval [CI], 2.72−7.40); but age had only borderline effects on PFS to MFS transitions. In contrast, infarct size exerted substantial effects on PFS to MFS transitions: small-size infarct correlated with a higher transition rate (rate ratio, 10.17; 95% CI, 5.25−20.13), whereas only a borderline effect on MFS to GFS transitions was found. The baseline functional state significantly affected the MFS to GFS transitions.

Conclusions

By using a multistate model, overall and patient-specific mean time to functional recovery to different functional states can be estimated and the effect of clinical predictors on functional transitions can be precisely quantified to predict patient-specific probability of functional recovery.     

Methadone metabolism and clearance are induced by nelfinavir despite inhibition of cytochrome P4503A (CYP3A) activity

Background

Methadone plasma concentrations are decreased by nelfinavir. Methadone clearance and the drug interactions have been attributed to CYP3A4, but actual mechanisms of methadone clearance and the nelfinavir interaction are unknown. We assessed nelfinavir effects on methadone pharmacokinetics and pharmacodynamics, intestinal and hepatic CYP3A4/5 activity, and intestinal P-glycoprotein transport activity. CYP3A4/5 and transporters were assessed using alfentanil and fexofenadine, respectively.

Methods

Twelve healthy HIV-negative volunteers underwent a sequential crossover. On three consecutive days they received oral alfentanil plus fexofenadine, intravenous alfentanil, and intravenous plus oral methadone. This was repeated after nelfinavir. Plasma and urine analytes were measured by mass spectrometry. Opioid effects were measured by pupil diameter change (miosis).

Results

Nelfinavir decreased intravenous and oral methadone plasma concentrations 40–50%. Systemic clearance, hepatic clearance, and hepatic extraction all increased 1.6- and 2-fold, respectively, for R- and S-methadone; apparent oral clearance increased 1.7- and 1.9-fold. Nelfinavir stereoselectively increased (S > R) methadone metabolism and metabolite formation clearance, and methadone renal clearance. Methadone bioavailability and P-glycoprotein activity were minimally affected. Nelfinavir decreased alfentanil systemic and apparent oral clearances 50 and 76%, respectively. Nelfinavir appeared to shift the methadone plasma concentration–effect (miosis) curve leftward and upward.

Conclusions

Nelfinavir induced methadone clearance by increasing renal clearance, and more so by stereoselectively increasing hepatic metabolism, extraction and clearance. Induction occurred despite 50% inhibition of hepatic CYP3A4/5 activity and more than 75% inhibition of first-pass CYP3A4/5 activity, suggesting little or no role for CYP3A in clinical methadone disposition. Nelfinavir may alter methadone pharmacodynamics, increasing clinical effects.     

哈乐联合奥昔布宁治疗前列腺增生逼尿肌不稳定

目的 评价哈乐联合奥昔布宁治疗前列腺增生(BPH)逼尿肌不稳定的有效性及安全性.方法 36例BPH伴下尿路症状患者经尿动力学检查证实膀胱出口轻至中度梗阻并逼尿肌不稳定.平均年龄64.2岁(55～73岁).患者随机分为2组,联合用药组口服哈乐0.2mg/d+奥昔布宁5mg,2次/d,对照组口服哈乐0.2mg/d,持续4周.比较2组治疗前后平均I-PSS、SSS、QOL评分以及尿流率、残余尿量.结果 2组无因药物副作用中途退出者.治疗前,联合用药组和对照组平均I-PSS、SSS、QOL评分、尿流率以及残余尿量分别为(23.2±1.6)、(13.3±1.3)、(4.2±0.9)、(10.3±4.1)mL/s、(21.2±4.3)mL和(24.1±2.3)、(12.8±5.3)、(4.5±1.7)、(11.2±2.9)mL/s、(24.6±3.8)mL,差别无显著性(P>0.01);治疗后2组平均I-PSS、SSS、QOL评分分别为(12.2±2.3)、(5.3±0.7)、(1.9±0.4)和(15.2±2.3)、(9.6±2.5)、(3.9±1.4),差别有显著性(P<0.01);平均尿流率和残余尿量分别为(15.8±3.3)mL/s、(10.8±4.3)mL和(16.6±4.1)mL/s、(12.8±3.1)mL,差别无显著性(P>0.01).说明联合用药可明显改善患者储尿期症状,对排尿功能的影响与对照组无明显差异.结论 哈乐联合奥营布宁可改善BPH逼尿肌不稳定患者的下尿路症状和生活质量.对轻至中度BOO患者,应用小剂量奥昔布宁是安全的.     

A critical examination of bifrontal electroconvulsive therapy: clinical efficacy, cognitive side effects, and directions for future research

Bifrontal (BF) electroconvulsive therapy (ECT), although researched less extensively than bitemporal (BT) or right unilateral (RUL) ECT, has been suggested to be comparable to the other 2 electrode placements with respect to clinical efficacy while resulting in less cognitive impairment than BT ECT. Imaging studies have indicated that seizures induced by BF ECT affect the brain differently than BT or RUL ECT, in that BF ECT increases cerebral blood flow in the frontal lobes more intensely than either of the other 2 placements. Therefore, it is possible that the cognitive impairment manifested after a course of BF ECT could also be different than the impairment seen with BT and RUL ECT. Research conducted on cognitive impairment from BF ECT to date has been inadequate due to the use of nonspecific cognitive measures (such as the Mini-Mental Status Examination) or an inordinate focus on memory functioning (which is believed to be mostly subsumed in the temporal lobes). Because BF ECT increases cerebral blood flow in the frontal lobes more intensely than either of the other placements, research must instead focus on investigating the possible effects of BF ECT on executive functioning, which is believed to be subsumed in the frontal lobes. This is especially important because of the established relationship between executive dysfunction and depression and also because of the increasing popularity of BF ECT.     

Examining the relationship between the reconstructed scales and the fake bad scale of the MMPI-2

This study explores the relationship between the Reconstructed (RC) scales and the Fake Bad Scale (FBS) of the MMPI-2 in the context of a personal injury population to demonstrate which RC scales are susceptible to symptom exaggeration. The sample consisted of 76 compensation-seeking participants who were assessed for neurocognitive dysfunction. A multiple regression analysis was performed to determine the association between the Reconstructed Scale T-scores with the FBS T-scores. Three of the nine RC scales (RC1, RC2, RC3) were significantly (p <. 05) associated with FBS, with RC7 demonstrating a strong trend (p =. 0526). These scale scores accounted for approximately 66% of the variation in the FBS score. The RC1 scale accounted for the most variation (R(2) =. 53). Results suggest that the RC scales are susceptible to exaggeration of somatic concerns and non-psychotic emotional distress.