Validation of the Patient Perception of Migraine Questionnaire

Objective: The purpose of this study was to assess the psychometric properties of the Patient Perception of Migraine Questionnaire (PPMQ), which measures patient satisfaction with migraine therapy. Methods and Data: The PPMQ was administered to 940 patients as part of a 3-month, multinational, open-label, clinical trial comparing the effects of oral naratriptan 2.5 mg with the patient's customary therapy for the treatment of migraine. Psychometric properties of the PPMQ were evaluated in terms of its latent factor structure, validity, reliability, sensitivity, and development of a scoring method. Classical Test theory and Item Response theory (IRT) modeling were both used to measure reliability. Results: The PPMQ was able to detect treatment differences (P > .001), and all items significantly correlated with diary ratings of headache pain (r = .18−.51, p > .0001) and the Medical Outcomes Short Form-36 pain scale (r = .27, p > .0001). A principal components factor analysis revealed that the items on the PPMQ were psychometrically distinct and unidimensional (loadings, 0.74–0.91), with the exclusion of two items. The reliability (i.e., internal item consistency) of the PPMQ post-trial was high in both treatment groups (Cronbach's α = 0.96). An IRT analysis also ensured the formation of homogenous items, which were stable on repeat administration. Items did not require weighting and can be simply summed to yield a total score. Conclusion: Based on the data from this one clinical trial, the 15-item PPMQ was shown to be a valid and reliable instrument that seems to efficiently and comprehensively measure patient perception of drug attributes in relation to the treatment of symptoms associated with migraine headaches

Design of price incentives for adjunct policy goals in formula funding for hospitals and health services

Background. Hospital policy involves multiple objectives: efficiency of service delivery, pursuit of high quality care, promoting access. Funding policy based on hospital casemix has traditionally been considered to be only about promoting efficiency. Discussion. Formula-based funding policy can be (and has been) used to pursue a range of policy objectives, not only efficiency. These are termed 'adjunct' goals. Strategies to incorporate adjunct goals into funding design must, implicitly or explicitly, address key decision choices outlined in this paper. Summary. Policy must be clear and explicit about the behaviour to be rewarded; incentives must be designed so that all facilities with an opportunity to improve have an opportunity to benefit; the reward structure is stable and meaningful; and the funder monitors performance and gaming

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

An End To Silence: Women Prisoners’ Handbook On Identifying And Addressing Sexual Misconduct, 2nd Ed.

The National Women’s Law Center is a non-profit organization that has been working since 1972 to advance and protect women’s legal rights. The Center focuses on major policy areas of importance to women and their families including education, employment, reproductive rights, health, family support and income security, with special attention given to the concerns of low-income women. As a legal arm of the women’s movement, the Center has litigated ground-breaking cases and filed briefs in landmark Supreme Court decisions; advocated before state and federal policymakers to shape legislation and policies affecting women’s lives; and educated the public about issues important to women. The Center’s legal expertise make it an important contributor to girls’ and women’s progress at school, at work and in almost every aspect of their lives. In 1990, the Center launched the Women in Prison Project to address the serious problems confronting women prisoners. The Project provides legal, counseling and advocacy services to over 1,500 women incarcerated by the District of Columbia Department of Corrections and the Federal Bureau of Prisons. In addition to its local direct services work, the Center works on the national level conducting public education and training, providing technical assistance to policymakers and advocates, developing resources and disseminating information on issues affecting women in conflict with the law. In 1993, the Center’s work with women prisoners prompted it to file class action litigation on behalf of all women incarcerated by the District of Columbia. In 1994, Judge June Green, of the U.S. District Court for the District of Columbia, found that women prisoners were subjected to sexual harassment and provided with programs and opportunities inferior to those provided to male prisoners. The Court found violations of the U.S. Constitution, federal statutory law and District of Columbia law and ordered broad remedial relief in the areas of sexual misconduct, obstetrical and gynecological care, education and vocational programs, and environmental safety. While portions of the Court’s order were overturned by an appellate court, the Court’s findings with regard to sexual misconduct remain. In light of the Court’s decision and the emergence of the issue of sexual misconduct nationally, the Center engaged in a three-pronged strategy which included enforcement of the Court’s order, technical assistance and training to women prisoners and corrections officials, and the development of materials for both prisoners and corrections workers. We believe that addressing sexual misconduct is at the core of assuring women’s safety in prison and that only a coordinated strategy that involves law and policy development, training of prisoners and corrections workers, and public education will reduce the occurrence of sexual misconduct

An End To Silence: Women Prisoners’ Handbook On Identifying And Addressing Sexual Misconduct, 2nd Ed.

The National Women’s Law Center is a non-profit organization that has been working since 1972 to advance and protect women’s legal rights. The Center focuses on major policy areas of importance to women and their families including education, employment, reproductive rights, health, family support and income security, with special attention given to the concerns of low-income women. As a legal arm of the women’s movement, the Center has litigated ground-breaking cases and filed briefs in landmark Supreme Court decisions; advocated before state and federal policymakers to shape legislation and policies affecting women’s lives; and educated the public about issues important to women. The Center’s legal expertise make it an important contributor to girls’ and women’s progress at school, at work and in almost every aspect of their lives. In 1990, the Center launched the Women in Prison Project to address the serious problems confronting women prisoners. The Project provides legal, counseling and advocacy services to over 1,500 women incarcerated by the District of Columbia Department of Corrections and the Federal Bureau of Prisons. In addition to its local direct services work, the Center works on the national level conducting public education and training, providing technical assistance to policymakers and advocates, developing resources and disseminating information on issues affecting women in conflict with the law. In 1993, the Center’s work with women prisoners prompted it to file class action litigation on behalf of all women incarcerated by the District of Columbia. In 1994, Judge June Green, of the U.S. District Court for the District of Columbia, found that women prisoners were subjected to sexual harassment and provided with programs and opportunities inferior to those provided to male prisoners. The Court found violations of the U.S. Constitution, federal statutory law and District of Columbia law and ordered broad remedial relief in the areas of sexual misconduct, obstetrical and gynecological care, education and vocational programs, and environmental safety. While portions of the Court’s order were overturned by an appellate court, the Court’s findings with regard to sexual misconduct remain. In light of the Court’s decision and the emergence of the issue of sexual misconduct nationally, the Center engaged in a three-pronged strategy which included enforcement of the Court’s order, technical assistance and training to women prisoners and corrections officials, and the development of materials for both prisoners and corrections workers. We believe that addressing sexual misconduct is at the core of assuring women’s safety in prison and that only a coordinated strategy that involves law and policy development, training of prisoners and corrections workers, and public education will reduce the occurrence of sexual misconduct