An economic evaluation of the randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo (the HI-Light Vitiligo Trial).

BACKGROUND: Economic evidence for vitiligo treatments is absent. OBJECTIVES: To determine the cost-effectiveness of (i) handheld narrowband ultraviolet B (NB-UVB) and (ii) a combination of topical corticosteroid (TCS) and NB-UVB compared with TCS alone for localized vitiligo. METHODS: Cost-effectiveness analysis alongside a pragmatic, three-arm, placebo-controlled randomized controlled trial with 9 months' treatment. In total 517 adults and children (aged ≥ 5 years) with active vitiligo affecting < 10% of skin were recruited from secondary care and the community and were randomized 1: 1: 1 to receive TCS, NB-UVB or both. Cost per successful treatment (measured on the Vitiligo Noticeability Scale) was estimated. Secondary cost-utility analyses measured quality-adjusted life-years using the EuroQol 5 Dimensions 5 Levels for those aged ≥ 11 years and the Child Health Utility 9D for those aged 5 to < 18 years. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: The mean ± SD cost per participant was £775 ± 83·7 for NB-UVB, £813 ± 111.4 for combination treatment and £600 ± 96·2 for TCS. In analyses adjusted for age and target patch location, the incremental difference in cost for combination treatment compared with TCS was £211 (95% confidence interval 188-235), corresponding to a risk difference of 10·9% (number needed to treat = 9). The incremental cost was £1932 per successful treatment. The incremental difference in cost for NB-UVB compared with TCS was £173 (95% confidence interval 151-196), with a risk difference of 5·2% (number needed to treat = 19). The incremental cost was £3336 per successful treatment. CONCLUSIONS: Combination treatment, compared with TCS alone, has a lower incremental cost per additional successful treatment than NB-UVB only. Combination treatment would be considered cost-effective if decision makers are willing to pay £1932 per additional treatment success.

Chronic urticaria in the real-life clinical practice setting in the UK: results from the noninterventional multicentre AWARE study.

BACKGROUND: Chronic urticaria (CU) is a skin condition characterized by repeated occurrence of itchy weals and/or angio-oedema for > 6 weeks. AIM: To provide data demonstrating the real-life burden of CU in the UK. METHODS: This UK subset of the worldwide, prospective, noninterventional AWARE study included patients aged 18-75 years diagnosed with H1-antihistamine (H1-AH)-refractory chronic spontaneous urticaria (CSU) for > 2 months. Baseline characteristics, disease activity, treatments, comorbidities and healthcare resource use were documented. Quality of life (QoL), work productivity and activity impairment were assessed. RESULTS: Baseline analysis included 252 UK patients. Mean age and body mass index were 45.0 years and 29.0 kg/m2 , respectively. Most patients were female (77.8%) and had moderate/severe disease activity (mean Urticaria Activity Score over 7 days was 18.4) and a 'spontaneous' component to their CU (73.4% CSU; 24.6% CSU and chronic inducible urticaria). Common comorbidities included depression/anxiety (24.6%), asthma (23.8%) and allergic rhinitis (12.7%). A previous treatment was recorded for 57.9% of patients. Mean Dermatology Life Quality Index score was 9.5, and patients reported impairments in work productivity and activity. Healthcare resource use was high. Severity of CSU was associated with female sex, obesity, anxiety and diagnosis. Only 28.5% of patients completed all nine study visits, limiting analysis of long-term treatment patterns and disease impact. CONCLUSIONS: Adult H1-AH-refractory patients with CU in the UK reported high rates of healthcare resource use and impairment in QoL, work productivity and activity at baseline. The differing structures of UK healthcare may explain the high study discontinuation rates versus other countries.

Activation of hepatic estrogen receptor-α increases energy expenditure by stimulating the production of fibroblast growth factor 21 in female mice.

OBJECTIVE: The endogenous estrogen 17ß-estradiol (E2) promotes metabolic homeostasis in premenopausal women. In a mouse model of post-menopausal metabolic syndrome, we reported that estrogens increased energy expenditure, thus preventing estrogen deficiency-induced adiposity. Estrogens' prevention of fat accumulation was associated with increased serum concentrations of fibroblast growth factor 21 (FGF21), suggesting that FGF21 participates in estrogens' promotion of energy expenditure. METHODS: We studied the effect of E2 on FGF21 production and the role of FGF21 in E2 stimulation of energy expenditure and prevention of adiposity, using female estrogen receptor (ER)- and FGF21-deficient mice fed a normal chow and a cohort of ovariectomized women from the French E3N prospective cohort study. RESULTS: E2 acting on the hepatocyte ERα increases hepatic expression and production of FGF21 in female mice. In vivo activation of ERα increases the transcription of Fgf21 via an estrogen response element outside the promoter of Fgf21. Treatment with E2 increases oxygen consumption and energy expenditure and prevents whole body fat accumulation in ovariectomized female WT mice. The effect of E2 on energy expenditure is not observed in FGF21-deficient mice. While E2 treatment still prevents fat accumulation in FGF21-deficient mice, this effect is decreased compared to WT mice. In an observational cohort of ovariectomized women, E2 treatment was associated with lower serum FGF21 concentrations, which may reflect a healthier metabolic profile. CONCLUSIONS: In female mice, E2 action on the hepatocyte ERα increases Fgf21 transcription and FGF21 production, thus promoting energy expenditure and partially decreasing fat accumulation.

Development of a time-stepping sediment budget model for assessing land use impacts in large river basins.

The use of river basin modelling to guide mitigation of non-point source pollution of wetlands, estuaries and coastal waters has become widespread. To assess and simulate the impacts of alternate land use or climate scenarios on river washload requires modelling techniques that represent sediment sources and transport at the time scales of system response. Building on the mean-annual SedNet model, we propose a new D-SedNet model which constructs daily budgets of fine sediment sources, transport and deposition for each link in a river network. Erosion rates (hillslope, gully and streambank erosion) and fine sediment sinks (floodplains and reservoirs) are disaggregated from mean annual rates based on daily rainfall and runoff. The model is evaluated in the Burdekin basin in tropical Australia, where policy targets have been set for reducing sediment and nutrient loads to the Great Barrier Reef (GBR) lagoon from grazing and cropping land. D-SedNet predicted annual loads with similar performance to that of a sediment rating curve calibrated to monitored suspended sediment concentrations. Relative to a 22-year reference load time series at the basin outlet derived from a dynamic general additive model based on monitoring data, D-SedNet had a median absolute error of 68% compared with 112% for the rating curve. RMS error was slightly higher for D-SedNet than for the rating curve due to large relative errors on small loads in several drought years. This accuracy is similar to existing agricultural system models used in arable or humid environments. Predicted river loads were sensitive to ground vegetation cover. We conclude that the river network sediment budget model provides some capacity for predicting load time-series independent of monitoring data in ungauged basins, and for evaluating the impact of land management on river sediment load time-series, which is challenging across large regions in data-poor environments.

Diagnosing symptomatic HIV-associated neurocognitive disorders: self-report versus performance-based assessment of everyday functioning.

Three types of HIV-associated neurocognitive disorders (HAND) exist that are distinguished by presence and severity of impairment in cognitive and everyday functioning. Although well-validated neurocognitive measures exist, determining impairment in everyday functioning remains a challenge. We aim to determine whether Self-Report measures of everyday functioning are as effective in characterizing HAND as Performance-Based measures. We assessed 674 HIV-infected participants with a comprehensive neurocognitive battery; 233 met criteria for a HAND diagnosis by having at least mild neurocognitive impairment. Functional decline was measured via Self-Report and Performance-Based measures. HAND diagnoses were determined according to published criteria using three approaches to assess functional decline: (1) Self-Report measures only, (2) Performance-Based measures only, and (3) Dual-method combining Self-Report and Performance-Based measures. The Dual-method classified the most symptomatic HAND, compared to either singular method. Singular method classifications were 76% concordant with each other. Participants classified as Performance-Based functionally impaired were more likely to be unemployed and more immunosuppressed, whereas those classified as Self-Report functionally impaired had more depressive symptoms. Multimodal methods of assessing everyday functioning facilitate detection of symptomatic HAND. Singular Performance-Based classifications were associated with objective functional and disease-related factors; reliance on Self-Report classifications may be biased by depressive symptoms.

Impact of long-term treatment with neurotoxic dideoxynucleoside antiretrovirals: implications for clinical care in resource-limited settings.

OBJECTIVES: A minority of HIV-infected patients taking an antiretroviral (ARV) regimen containing dideoxynucleosides (d-drugs) such as stavudine (d4T) and didanosine (DDI) experiences dose-limiting neuropathic pain and paraesthesias, usually within weeks of starting these drugs. Because d-drugs are among the few affordable options available in developing countries, continuing d-drug therapy would be a desirable strategy for many HIV-infected individuals. Therefore, we evaluated the safety of continuing d-drug therapy. METHODS: In a US cohort, we compared the rates of worsening neuropathic symptoms and signs in HIV-infected individuals on stable ARV regimens that did (n=252) or did not (n=250) include d-drugs. Rates of worsening were compared using proportional hazards model and the log-rank test. RESULTS: The risk ratios (RR) were not significantly larger for worsening neuropathy signs [0.94; 95% confidence interval (CI) 0.84-1.07] or symptoms (0.99; 95% CI 0.88-1.14) in patients taking d-drugs continuously compared to those not taking d-drugs. CONCLUSIONS: Continued d-drug exposure among patients tolerating an initial trial did not increase the risk of worsening neuropathy compared to non-d-drug-containing regimens. If applicable in developing countries, these findings suggest that in most patients d-drugs can be continued safely in the long term without increasing the risk of worsening neuropathy.

Magnetic resonance imaging for in vivo assessment of three-dimensional patellar tracking.

We have developed a non-invasive measurement technique which can ultimately be used to quantify three-dimensional patellar kinematics of human subjects for a range of static positions of loaded flexion and assessed its accuracy. Knee models obtained by segmenting and reconstructing one high-resolution scan of the knee were registered to bone outlines obtained by segmenting fast, low-resolution scans of the knee in static loaded flexion. We compared patellar tracking measurements made using the new method to measurements made using Roentgen stereophotogrammetric analysis in three cadaver knee specimens loaded through a range of flexion in a test rig. The error in patellar spin and tilt measurements was less than 1.02 degrees and the error in lateral patellar shift was 0.88 mm. Sagittal plane scans provided more accurate final measurements of patellar spin and tilt, whereas axial plane scans provided more accurate measurements of lateral translation and patellar flexion. Halving the number of slices did not increase measurement error significantly, which suggests that scan times can be reduced without reducing accuracy significantly. The method is particularly useful for multiple measurements on the same subject because the high-resolution bone-models need only be created once; thus, the potential variability in coordinate axes assignment and model segmentation during subsequent measurements is removed.

A multimodal assessment of driving performance in HIV infection.

OBJECTIVE: To examine if HIV-seropositive (HIV+) individuals are at risk for impaired driving. METHODS: Sixty licensed drivers (40 HIV+, 20 HIV-) completed a neuropsychological (NP) test battery and driving assessments. Eleven HIV+ subjects were NP-impaired. Driving-related skills were assessed using 1) two driving simulations (examining accident avoidance and navigational abilities), 2) the Useful Field of View (UFOV) test, and 3) an on-road evaluation. RESULTS: HIV+ NP-impaired subjects had greater difficulty than cognitively intact subjects on all driving measures, whereas the HIV- and HIV+ NP-normal groups performed similarly. On the UFOV, the HIV+ NP-impaired group had worse performance on Visual Processing and Divided Attention tasks but not in overall risk classification. They also had a higher number of simulator accidents (1.3 vs 2.0; p = 0.03), were less efficient at completing the navigation task (3.2 vs 9.2 blocks; p = 0.001), and were more likely to fail the on-road evaluation (6 vs 36%; p = 0.02). Impairment in Executive Functioning was the strongest NP predictor of failing the on-road drive test. NP performance and both simulations independently contributed to a model predicting 48% of the variance in on-road performance. CONCLUSION: HIV+ NP-impaired individuals are at increased risk for on-road driving impairments, whereas HIV+ individuals with normal cognition are not at a significantly higher risk than HIV- subjects. Executive Functioning is most strongly associated with impaired on-road performance. Cognitive and simulator testing may each provide data in identifying driving-impaired individuals.

Accurate assessment of patellar tracking using fiducial and intensity-based fluoroscopic techniques.

Accuracies of a point-based and an intensity-based fluoroscopic methods of assessing patella tracking were determined by comparing the pattern of patellar motion with respect to orientation (flexion, internal rotation, and lateral tilt) and translation (lateral, proximal, and anterior) with the pattern of patellar motion measured using Roentgen stereophotogrammetric analysis in three cadaver knee specimens. Each pose in the patellar motion could be obtained from single as well as multiple calibrated fluoroscopic images. The errors using the intensity-based method were slightly higher than those of the point-based method, but they appear to be sufficiently low to detect clinically significant differences in patellar kinematics.

Risk selection in the Massachusetts State employee health insurance program.

Using the Diagnostic Cost Group (DCG) model developed from a national sample, we examine biased selection among one fee-for-service (FFS) plan, one preferred provider organization, and several health maintenance organizations (HMOs) in Massachusetts. The proportions of enrollees in low-risk groups are higher in the HMO plans and lower in the FFS plan. The average age in the FFS plan is 9 years greater than that in the HMO plans. Actual premiums are not consistent with risk levels among HMO plans, resulting in gains in some HMO plans and losses in others as high as 20% compared to expected expenses as computed by the DCG model.

Financial services employees' experience of peer-led and clinician-led critical incident stress debriefing following armed robberies.

This study investigates financial services employees' experience of critical incident stress debriefing (CISD) and their views about peers and clinicians as facilitators. Semi-structured interview accounts of four participants who had experienced both peer-led and clinician-led CISD were analyzed using grounded theory. A core category, ambivalence, permeated each interview and divided into two poles: pathologizing and normalizing. The most frequently occurring sub-category was a dislike of professionalism. Participants preferred the peer debriefer who was perceived to have more personal involvement and with whom they felt more empowered and understood. The findings suggest that the status of the debriefer as 'peer' or 'clinician' may be a crucial variable in the effectiveness of CISD and should be considered when reviewing the outcome literature.

Formal risk adjustment by private employers.

This paper explores explanations for why few private employers have adopted formal risk adjustment. The lack of data, challenges of using highly imperfect signals, and absence of market power are not compelling explanations. Alternative strategies that reduce selection problems are clearly important. The central argument is that U.S. health markets are not in equilibrium, but rather are changing rapidly. Since many agents-consumers, employers, health plans, and providers--do not currently demand formal risk adjustment, it is not surprising that adoption has been slow. Recent changes in health plan markets may change the demand and accelerate future adoption.

Measuring population health risks using inpatient diagnoses and outpatient pharmacy data.

OBJECTIVE: To examine and evaluate models that use inpatient encounter data and outpatient pharmacy claims data to predict future health care expenditures. DATA SOURCES/STUDY DESIGN: The study group was the privately insured under-65 population in the 1997 and 1998 MEDSTAT Market Scan (R) Research Database. Pharmacy and disease profiles, created from pharmacy claims and inpatient encounter data, respectively, were used separately and in combination to predict each individual's subsequent-year health care expenditures. PRINCIPAL FINDINGS: The inpatient-diagnosis model predicts well for the low-hospitalization under-65 populations, explaining 8.4 percent of future individual total cost variation. The pharmacy-based and in patient-diagnosis models perform comparably overall, with pharmacy data better able to split off a group of truly low-cost people and inpatient diagnoses better able to find a small group with extremely high future costs. The model th at uses both kinds of data performed significantly better than either model alone, with an R2 value of 11.8 percent . CONCLUSIONS: Comprehensive pharmacy and inpatient diagnosis classification systems are each helpful for discriminating among people according to their expected costs. Properly organized and in combination these data are promising predictors of future costs.

Finding future high-cost cases: comparing prior cost versus diagnosis-based methods.

OBJECTIVE: To examine the value of two kinds of patient-level dat a (cost and diagnoses) for identifying a very small subgroup of a general population with high future costs that may be mitigated with medical management. DATA SOURCES: The study used the MEDSTAT Market Scan (R) Research Database, consisting of inpatient and ambulatory health care encounter records for individuals covered by employee- sponsored benefit plans during 1997 and 1998. STUDY DESIGN: Prior cost and a diagnostic cost group (DCG) risk model were each used with 1997 data to identify 0.5-percent-sized "top groups" of people most likely to be expensive in 1998. We compared the distributions of people, cost, and diseases commonly targeted for disease management for people in the two top groups and, as a bench mark, in the full population. PRINCIPAL FINDINGS: the prior cost- and DCG-identified top groups overlapped by only 38 percent. Each top group consisted of people with high year-two costs and high rates of diabetes, heart failure, major lung disease, and depression. The DCG top group identified people who are both somewhat more expensive ($27,292 vs. $25,981) and more likely ( 49.4 percent vs. 43.8 percent ) th an the prior-cost top group to have at least one of the diseases commonly targeted for disease management. The overlap group average cost was $46,219. CONCLUSIONS: Diagnosis-based risk models are at least as powerful as prior cost for identifying people who will be expensive. Combined cost and diagnostic data are even more powerful and more operation ally useful, especially because the diagnostic information identifies the medical problems that may be managed to achieve better out comes and lower costs.