Maintaining Response Rates In Longitudinal Studies

A recognized problem in mounting longitudinal surveys concerns the costs and difficulties in maintaining response rates over time. This article details the techniques used to minimize response loss in a longitudinal study which maintained an 89% response rate over five interviews covering a fifteen-year period. These techniques centered on two problems common to all longitudinal studies: the difficulties involved in relocating respondents for subsequent interviews, and the necessity of maintaining respondent cooperation over repeated interviews.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69083/2/10.1177_004912418000900104.pd

On the energy of gamma-ray bursts

We show that gamma-ray burst (GRB) afterglow observations strongly suggest, within the fireball model framework, that radiating electrons are shock accelerated to a power-law energy distribution, with universal index p \approx 2.2, and that the fraction of shock energy carried by electrons, \xi_e, is universal and close to equipartition, \xi_e ~ 1/3. For universal p and \xi_e, a single measurement of the X-ray afterglow flux on the time scale of a day provides a robust estimate of the fireball energy per unit solid angle, \epsilon, averaged over a conical section of the fireball of opening angle \theta ~ 0.1. Applying our analysis to BeppoSAX afterglow data we find that: (i) Fireball energies are in the range of 4\pi\epsilon=10^{51.5} to 10^{53.5} erg; (ii) The ratio of observed $\gamma$-ray to total fireball energy per unit solid angle, \epsilon_\gamma / \epsilon, is of order unity, satisfying abs[log10(\epsilon_\gamma/\epsilon)]<0.5; (iii) If fireballs are jet like, their opening angle should satisfy \theta>=0.1. Our results imply that if typical opening angles are \theta ~ 0.1, a value consistent with our analysis, the total energy associated with a GRB event is in the range of 10^{50} erg to 10^{51.5} erg.Comment: 16 pages; Submitted to Ap

Enhanced Identification of Postoperative Infections among Outpatients

Claims data complement other data sources for identification of surgical site infections following breast surgery and cesarean section

Safety and efficacy of VB-111, an anticancer gene therapy, in patients with recurrent glioblastoma: results of a phase I/II study.

BackgroundVB-111 is a non-replicating adenovirus carrying a Fas-chimera transgene, leading to targeted apoptosis of tumor vascular endothelium and induction of a tumor-specific immune response. This phase I/II study evaluated the safety, tolerability, and efficacy of VB-111 with and without bevacizumab in recurrent glioblastoma (rGBM).MethodsPatients with rGBM (n = 72) received VB-111 in 4 treatment groups: subtherapeutic (VB-111 dose escalation), limited exposure (LE; VB-111 monotherapy until progression), primed combination (VB-111 monotherapy continued upon progression with combination of bevacizumab), and unprimed combination (upfront combination of VB-111 and bevacizumab). The primary endpoint was median overall survival (OS). Secondary endpoints were safety, overall response rate, and progression-free survival (PFS).ResultsVB-111 was well tolerated. The most common adverse event was transient mild-moderate fever. Median OS time was significantly longer in the primed combination group compared with both LE (414 vs 223 days; hazard ratio [HR], 0.48; P = 0.043) and unprimed combination (414 vs 141.5 days; HR, 0.24; P = 0.0056). Patients in the combination phase of the primed combination group had a median PFS time of 90 days compared with 60 in the LE group (HR, 0.36; P = 0.032), and 63 in the unprimed combination group (P = 0.72). Radiographic responders to VB-111 exhibited characteristic, expansive areas of necrosis in the areas of initial enhancing disease.ConclusionsPatients with rGBM who were primed with VB-111 monotherapy that continued after progression with the addition of bevacizumab showed significant survival and PFS advantage, as well as specific imaging characteristics related to VB-111 mechanism of action. These results warrant further assessment in a randomized controlled study

Common variants in the ATM, BRCA1, BRCA2, CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Introduction Certain rare, familial mutations in the ATM, BRCA1, BRCA2, CHEK2 or TP53 genes increase susceptibility to breast cancer but it has not, until now, been clear whether common polymorphic variants in the same genes also increase risk. Methods We have attempted a comprehensive, single nucleotide polymorphism (SNP)- and haplotype-tagging association study on each of these five genes in up to 4,474 breast cancer cases from the British, East Anglian SEARCH study and 4,560 controls from the EPIC-Norfolk study, using a two-stage study design. Nine tag SNPs were genotyped in ATM, together with five in BRCA1, sixteen in BRCA2, ten in CHEK2 and five in TP53, with the aim of tagging all other known, common variants. SNPs generating the common amino acid substitutions were specifically forced into the tagging set for each gene. Results No significant breast cancer associations were detected with any individual or combination of tag SNPs. Conclusion It is unlikely that there are any other common variants in these genes conferring measurably increased risks of breast cancer in our study population

Expanding contraceptive options for PMTCT clients: a mixed methods implementation study in Cape Town, South Africa

Abstract Background Clients of prevention of mother-to-child transmission (PMTCT) services in South Africa who use contraception following childbirth rely primarily on short-acting methods like condoms, pills, and injectables, even when they desire no future pregnancies. Evidence is needed on strategies for expanding contraceptive options for postpartum PMTCT clients to include long-acting and permanent methods. Methods We examined the process of expanding contraceptive options in five health centers in Cape Town providing services to HIV-positive women. Maternal/child health service providers received training and coaching to strengthen contraceptive counseling for postpartum women, including PMTCT clients. Training and supplies were introduced to strengthen intrauterine device (IUD) services, and referral mechanisms for female sterilization were reinforced. We conducted interviews with separate samples of postpartum PMTCT clients (265 pre-intervention and 266 post-intervention) to assess knowledge and behaviors regarding postpartum contraception. The process of implementing the intervention was evaluated through systematic documentation and interpretation using an intervention tracking tool. In-depth interviews with providers who participated in study-sponsored training were conducted to assess their attitudes toward and experiences with promoting voluntary contraceptive services to HIV-positive clients. Results Following the intervention, 6% of interviewed PMTCT clients had the desired knowledge about the IUD and 23% had the desired knowledge about female sterilization. At both pre- and post-intervention, 7% of clients were sterilized and IUD use was negligible; by comparison, 75% of clients used injectables. Intervention tracking and in-depth interviews with providers revealed intervention shortcomings and health system constraints explaining the failure to produce intended effects. Conclusions The intervention failed to improve PMTCT clients’ knowledge about the IUD and sterilization or to increase use of those methods. To address the family planning needs of postpartum PMTCT clients in a way that is consistent with their fertility desires, services must expand the range of contraceptive options to include long-acting and permanent methods. In turn, to ensure consistent access to high quality family planning services that are effectively linked to HIV services, attention must also be focused on resolving underlying health system constraints weakening health service delivery more generally

Effect of natalizumab on disease progression in secondary progressive multiple sclerosis (ASCEND). a phase 3, randomised, double-blind, placebo-controlled trial with an open-label extension

Background: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. Methods: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2). Enrolled patients aged 18–58 years were natalizumab-naive and had secondary progressive multiple sclerosis for 2 years or more, disability progression unrelated to relapses in the previous year, and Expanded Disability Status Scale (EDSS) scores of 3·0–6·5. In part 1, patients from 163 sites in 17 countries were randomly assigned (1:1) to receive 300 mg intravenous natalizumab or placebo every 4 weeks for 2 years. Patients were stratified by site and by EDSS score (3·0–5·5 vs 6·0–6·5). Patients completing part 1 could enrol in part 2, in which all patients received natalizumab every 4 weeks until the end of the study. Throughout both parts, patients and staff were masked to the treatment received in part 1. The primary outcome in part 1 was the proportion of patients with sustained disability progression, assessed by one or more of three measures: the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT). The primary outcome in part 2 was the incidence of adverse events and serious adverse events. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01416181. Findings: Between Sept 13, 2011, and July 16, 2015, 889 patients were randomly assigned (n=440 to the natalizumab group, n=449 to the placebo group). In part 1, 195 (44%) of 439 natalizumab-treated patients and 214 (48%) of 448 placebo-treated patients had confirmed disability progression (odds ratio [OR] 0·86; 95% CI 0·66–1·13; p=0·287). No treatment effect was observed on the EDSS (OR 1·06, 95% CI 0·74–1·53; nominal p=0·753) or the T25FW (0·98, 0·74–1·30; nominal p=0·914) components of the primary outcome. However, natalizumab treatment reduced 9HPT progression (OR 0·56, 95% CI 0·40–0·80; nominal p=0·001). In part 1, 100 (22%) placebo-treated and 90 (20%) natalizumab-treated patients had serious adverse events. In part 2, 291 natalizumab-continuing patients and 274 natalizumab-naive patients received natalizumab (median follow-up 160 weeks [range 108–221]). Serious adverse events occurred in 39 (13%) patients continuing natalizumab and in 24 (9%) patients initiating natalizumab. Two deaths occurred in part 1, neither of which was considered related to study treatment. No progressive multifocal leukoencephalopathy occurred. Interpretation: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component. Longer-term trials are needed to assess whether treatment of secondary progressive multiple sclerosis might produce benefits on additional disability components. Funding: Biogen