Longitudinal assessment of utilities in patients with migraine: an analysis of erenumab randomized controlled trials

BACKGROUND: Cost-effectiveness analyses in patients with migraine require estimates of patients’ utility values and how these relate to monthly migraine days (MMDs). This analysis examined four different modelling approaches to assess utility values as a function of MMDs. METHODS: Disease-specific patient-reported outcomes from three erenumab clinical studies (two in episodic migraine [NCT02456740 and NCT02483585] and one in chronic migraine [NCT02066415]) were mapped to the 5-dimension EuroQol questionnaire (EQ-5D) as a function of the Migraine-Specific Quality of Life Questionnaire (MSQ) and the Headache Impact Test (HIT-6™) using published algorithms. The mapped utility values were used to estimate generic, preference-based utility values suitable for use in economic models. Four models were assessed to explain utility values as a function of MMDs: a linear mixed effects model with restricted maximum likelihood (REML), a fractional response model with logit link, a fractional response model with probit link and a beta regression model. RESULTS: All models tested showed very similar fittings. Root mean squared errors were similar in the four models assessed (0.115, 0.114, 0.114 and 0.114, for the linear mixed effect model with REML, fractional response model with logit link, fractional response model with probit link and beta regression model respectively), when mapped from MSQ. Mean absolute errors for the four models tested were also similar when mapped from MSQ (0.085, 0.086, 0.085 and 0.085) and HIT-6 and (0.087, 0.088, 0.088 and 0.089) for the linear mixed effect model with REML, fractional response model with logit link, fractional response model with probit link and beta regression model, respectively. CONCLUSIONS: This analysis describes the assessment of longitudinal approaches in modelling utility values and the four models proposed fitted the observed data well. Mapped utility values for patients treated with erenumab were generally higher than those for individuals treated with placebo with equivalent number of MMDs. Linking patient utility values to MMDs allows utility estimates for different levels of MMD to be predicted, for use in economic evaluations of preventive therapies. TRIAL REGISTRATION: ClinicalTrials.gov numbers of the trials used in this study: STRIVE, NCT02456740 (registered May 14, 2015), ARISE, NCT02483585 (registered June 12, 2015) and NCT02066415 (registered Feb 17, 2014)

Decline in Survival After Liver Transplantation

Twenty-three recent cases of orthotopic liver transplantation were individually reviewed in an effort to determine why survival had declined from the 50% one-year survival rate of an immediately precedent series. In the series of 23, only six (26%) achieved one-year survival. Faulty case selection, technical complications, the use of damaged organs, and complications of immunosuppression were the main causes of death. Attention was directed to the possible use of preoperative lymphoid depletion to improve the effectiveness and safety of immunosuppression. © 1980, American Medical Association. All rights reserved

A Phylogenetic Analysis of HIV-1 Sequences in Kiev: Findings among Key Populations

BACKGROUND: The HIV epidemic in Ukraine has been driven by a rapid rise among people who inject drugs, but recent studies have shown an increase through sexual transmission. METHODS: Protease and RT sequences from 876 new HIV diagnoses (April 2013 - March 2015) in Kiev were linked to demographic data. We constructed phylogenetic trees for 794 subtype A1 and 64 subtype B sequences and identified factors associated with transmission clustering. Clusters were defined as ≥ 2 sequences, ≥ 80% local branch support and maximum genetic distance of all sequence pairs in the cluster ≤ 2.5%. Recent infection was determined through the LAg avidity EIA assay. Sequences were analysed for transmitted drug resistance (TDR) mutations. RESULTS: 30% of subtype A1 and 66% of subtype B sequences clustered. Large clusters (maximum 11 sequences) contained mixed risk groups. In univariate analysis, clustering was significantly associated with subtype B compared to A1 (OR 4.38 [95% CI 2.56-7.50]), risk group (OR 5.65 [3.27-9.75]) for men who have sex with men compared to heterosexual males, recent, compared to long-standing, infection (OR 2.72 [1.64-4.52]), reported sex work contact (OR 1.93 [1.07-3.47]) and younger age groups compared to age ≥36 (OR 1.83 [1.10-3.05] for age ≤25). Females were associated with lower odds of clustering than heterosexual males (OR 0.49 [0.31-0.77]). In multivariate analysis, risk group, subtype and age group were independently associated with clustering (p<0.001, p=0.007 and p=0.033). 18 sequences (2.1%) indicated evidence of TDR. CONCLUSIONS: Our findings suggest high levels of transmission and bridging between risk groups

Surfing the π-clouds for Non-covalent Interactions: A comparative Study of Arenes versus Alkenes

A comparative study by NMR spectroscopy using molecular balances indicates that non-covalent functional group interactions with an arene dominate over those with an alkene and a p-facial intramolecular hydrogen bond from a hydroxyl group to an arene is favoured by ~1.2 kJ mol-1. The strongest interaction observed in this study is with the cyano group and analysis of the series of Et, CH=CH2, C≡CH and C≡N groups is indicative of a weak long range electrostatic interaction and a correlation with the electrophilicity of the Ca atom of the Y substituent. Changes in the free energy differences of conformers show a linear dependence on the solvent hydrogen bond acceptor parameter β

The role of mothers-in-law in antenatal care decision-making in Nepal: a qualitative study

Background Antenatal care (ANC) has been recognised as a way to improve health outcomes for pregnant women and their babies. However, only 29% of pregnant women receive the recommended four antenatal visits in Nepal but reasons for such low utilisation are poorly understood. As in many countries of South Asia, mothers-in-law play a crucial role in the decisions around accessing health care facilities and providers. This paper aims to explore the mother-in-law’s role in (a) her daughter-in-law’s ANC uptake; and (b) the decision-making process about using ANC services in Nepal. Methods In-depth interviews were conducted with 30 purposively selected antenatal or postnatal mothers (half users, half non-users of ANC), 10 husbands and 10 mothers-in-law in two different (urban and rural) communities. Results Our findings suggest that mothers-in-law sometime have a positive influence, for example when encouraging women to seek ANC, but more often it is negative. Like many rural women of their generation, all mothers-in-law in this study were illiterate and most had not used ANC themselves. The main factors leading mothers-in-law not to support/ encourage ANC check ups were expectations regarding pregnant women fulfilling their household duties, perceptions that ANC was not beneficial based largely on their own past experiences, the scarcity of resources under their control and power relations between mothers-in-law and daughters-in-law. Individual knowledge and social class of the mothers-in-law of users and non-users differed significantly, which is likely to have had an effect on their perceptions of the benefits of ANC. Conclusion Mothers-in-law have a strong influence on the uptake of ANC in Nepal. Understanding their role is important if we are to design and target effective community-based health promotion interventions. Health promotion and educational interventions to improve the use of ANC should target women, husbands and family members, particularly mothers-in-law where they control access to family resources

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up

Asset pricing with downside liquidity risks

© 2016 INFORMS. We develop a parsimonious liquidity-adjusted downside capital asset pricing model to investigate whether phenomena such as downward liquidity spirals and flights to liquidity impact expected asset returns.We find strong empirical support for the model. Downside liquidity risk (sensitivity of stock liquidity to negative market returns) has an economically meaningful return premium that is 10 times larger than its symmetric analogue. The expected liquidity level and downside market risk are also associated with meaningful return premiums. Downside liquidity risk and its associated premium are higher during periods of low marketwide liquidity and for stocks that are relatively small, illiquid, volatile, and have high book-to-market ratios. These results are consistent with investors requiring compensation for holding assets susceptible to adverse liquidity phenomena. Our findings suggest that mitigation of downside liquidity risk can lower firms' cost of capital