Relevant gender differences in epidemiological profile, exposure to first antiretroviral regimen and survival in the Spanish AIDS Research Network Cohort.

BACKGROUND The possible differences in the disease spectrum and prognosis of HIV infection in women and men is a major point of concern. Women are under-represented in randomized clinical trials and in some cohorts. Discordant results have often been obtained depending on the setting. METHODS We assessed gender differences in clinical and epidemiological features, antiretroviral treatment (ART) exposure and survival in two multicentre cohorts of HIV-positive subjects in Spain: CoRIS-MD and CoRIS. Competing risk regression models were used to assess gender effect on time to start ART and time to first ART change, and a Cox regression model to estimate gender effect on time to death. RESULTS Between January 1996 and December 2008, 1,953 women and 6,072 men naive to ART at study entry were included. The trend analysis over time showed the percentage of women in the younger (<20 years) and older (>50 years) strata increased significantly (P<0.001) from 0.5% and 1.8% in 1996 to 4.9% and 4.2% in 2008, respectively. By competing risk analysis women started ART earlier than men (adjusted subhazard ratio [ASHR] 1.21, 95% CI 1.11, 1.31) in CoRIS cohort, while in CoRIS-MD none of these differences were observed. In both cohorts women showed a shorter time to the first ART change (ASHR 1.10, 95% CI 1.01, 1.19). Pregnancy and patient's/physician's decisions as reasons for changing were more frequent in women than in men in CoRIS. In the Cox regression model, gender was not associated with differences in survival. CONCLUSIONS In two large cohorts in Spain, we observed relevant gender differences in epidemiological characteristics and antiretroviral exposure outcomes, while survival differences were not attributable to gender.

What process research tells us about brief intervention efficacy.

ISSUE: This article explores mechanisms of the efficacy of brief intervention (BI). APPROACH: We conducted a BI trial at the emergency department of the Lausanne University Hospital, of whom 987 at-risk drinkers were randomised into BI and control groups. The overall results demonstrated a general decrease in alcohol use with no differences across groups. The intention to change was explored among 367 patients who completed BI. Analyses of 97 consecutive tape-recorded sessions explored patient and counsellor talks during BI, and their relationship to alcohol use outcome. KEY FINDINGS: Evaluation of the articulation between counsellor behaviours and patient language revealed a robust relationship between counsellor motivational interviewing (MI) skills and patient change talk during the intervention. Further exploration suggested that communication characteristics of patients during BI predicted changes in alcohol consumption 12 months later. Moreover, despite systematic training, important differences in counsellor performance were highlighted. Counsellors who had superior MI skills achieved better outcomes overall, and maintained efficacy across all levels of patient ability to change, whereas counsellors with inferior MI skills were effective mostly with patients who had higher levels of ability to change. Finally, the descriptions of change talk trajectories within BI and their association with drinking 12 months later showed that final states differed from initial states, suggesting an impact resulting from the progression of change talk during the course of the intervention. IMPLICATION: These findings suggest that BI should focus on the general MI attitude of counsellors who are capable of eliciting beneficial change talk from patients. [Daeppen J-B, Bertholet N, Gaume J. What process research tells us about brief intervention efficacy.

Outcomes of patients on dual-boosted PI regimens: experience of the Swiss HIV cohort study.

Dual-boosted protease inhibitors (DBPI) are an option for salvage therapy for HIV-1 resistant patients. Patients receiving a DBPI in the Swiss HIV Cohort Study between January1996 and March 2007 were studied. Outcomes of interest were viral suppression at 24 weeks. 295 patients (72.5%) were on DBPI for over 6 months. The median duration was 2.2 years. Of 287 patients who had HIV-RNA >400 copies/ml at the start of the regimen, 184 (64.1%) were ever suppressed while on DBPI and 156 (54.4%) were suppressed within 24 weeks. The median time to suppression was 101 days (95% confidence interval 90-125 days). The median number of past regimens was 6 (IQR, 3-8). The main reasons for discontinuing the regimen were patient's wish (48.3%), treatment failure (22.5%), and toxicity (15.8%). Acquisition of HIV through intravenous drug use and the use of lopinavir in combination with saquinavir or atazanavir were associated with an increased likelihood of suppression within 6 months. Patients on DBPI are heavily treatment experienced. Viral suppression within 6 months was achieved in more than half of the patients. There may be a place for DBPI regimens in settings where more expensive alternates are not available.

Examining non-response bias in substance use research-Are late respondents proxies for non-respondents?

BACKGROUND: Non-response is a major concern among substance use epidemiologists. When differences exist between respondents and non-respondents, survey estimates may be biased. Therefore, researchers have developed time-consuming strategies to convert non-respondents to respondents. The present study examines whether late respondents (converted former non-participants) differ from early respondents, non-consenters or silent refusers (consent givers but non-participants) in a cohort study, and whether non-response bias can be reduced by converting former non-respondents. METHODS: 6099 French- and 5720 German-speaking Swiss 20-year-old males (more than 94% of the source population) completed a short questionnaire on substance use outcomes and socio-demographics, independent of any further participation in a cohort study. Early respondents were those participating in the cohort study after standard recruitment procedures. Late respondents were non-respondents that were converted through individual encouraging telephone contact. Early respondents, non-consenters and silent refusers were compared to late respondents using logistic regressions. Relative non-response biases for early respondents only, for respondents only (early and late) and for consenters (respondents and silent refusers) were also computed. RESULTS: Late respondents showed generally higher patterns of substance use than did early respondents, but lower patterns than did non-consenters and silent refusers. Converting initial non-respondents to respondents reduced the non-response bias, which might be further reduced if silent refusers were converted to respondents. CONCLUSION: Efforts to convert refusers are effective in reducing non-response bias. However, converted late respondents cannot be seen as proxies of non-respondents, and are at best only indicative of existing response bias due to persistent non-respondents.

Evaluating Direct and Indirect Economic Outcomes of the 2008 Iowa Weather‐Related Disasters

This research seeks to fill some of the gaps in understanding the local, regional, and statewide economic consequences of the disasters of 2008. This report evaluates sets of population, unemployment, employment, business firms, and trade patterns over time in an attempt to discern the household consumption and business productivity disruptions caused by the weather disasters of 2008.

Systematic review of population pharmacokinetic analyses of imatinib and relationships with treatment outcomes

Several population pharmacokinetic (PPK) analyses of the anticancer drug imatinib have been performed to investigate different patient populations and covariate effects. The present analysis offers a systematic qualitative and quantitative summary and comparison of those. Its primary objective was to provide useful information for evaluating the expectedness of imatinib plasma concentration measurements in the frame of therapeutic drug monitoring. The secondary objective was to review clinically important concentration-effect relationships to provide help in evaluating the potential suitability of plasma concentration values. Nine PPK models describing total imatinib plasma concentration were identified. Parameter estimates were standardized to common covariate values whenever possible. Predicted median exposure (Cmin) was derived by simulations and ranged between models from 555 to 1388 ng/mL (grand median: 870 ng/mL and interquartile "reference" range: 520-1390 ng/mL). Covariates of potential clinical importance (up to 30% change in pharmacokinetic predicted by at least 1 model) included body weight, albumin, α1 acid glycoprotein, and white blood cell count. Various other covariates were included but were statistically not significant or seemed clinically less important or physiologically controversial. Concentration-response relationships had more importance below the average reference range and concentration-toxicity relationships above. Therapeutic drug monitoring-guided dosage adjustment seems justified for imatinib, but a formal predictive therapeutic range remains difficult to propose in the absence of prospective target concentration intervention trials. To evaluate the expectedness of a drug concentration measurement in practice, this review allows comparison of the measurement either to the average reference range or to a specific range accounting for individual patient characteristics. For future research, external PPK model validation or meta-model development should be considered.

Impact of HLA A2 and cytomegalovirus serostatus on outcomes in patients with leukemia following matched-sibling myeloablative allogeneic hematopoietic cell transplantation.

BACKGROUND AND OBJECTIVES: Donor cytomegalovirus seropositivity was reported to improve leukemia outcomes in HLA-A2 identical hematopoietic cell transplant (HCT) recipients, due to a possible cross-reactivity of donor HLA-A2-restricted CMV-specific T cells with minor histocompatibility (H) antigen of recipient cells. This study analyzed the role of donor CMV serostatus and HLA-A2 status on leukemia outcomes in a large population of HLA-identical HCT recipients. DESIGN AND METHODS: Leukemia patients transplanted between 1992 and 2003 at the Fred Hutchinson Cancer Research Center were categorized as standard risk [leukemia first remission, chronic myeloid leukemia in chronic phase (CML-CP)] and high risk (advanced disease) patients. Time-to-event analysis was used to evaluate the risk of relapse and death associated with HLA-A2 status and donor CMV serostatus. RESULTS: In standard risk patients, acute leukemia (p<0.001) and sex mismatch (female to male, p=0.004)) independently increased the risk of death, while acute leukemia increased the risk of relapse (p<0.001). In high risk patients acute leukemia (p=0.01), recipient age > or = 40 (p=0.005) and herpes simplex virus (HSV) seropositivity (p<0.001) significantly increased the risk death; HSV seropositivity (p=0.006) increased the risk of relapse. Donor CMV serostatus had no significant effect on mortality or relapse in any HLA group. INTERPRETATION AND CONCLUSION: This epidemiological study did not confirm the previously reported effect of donor CMV serostatus on the outcomes of leukemia in HLA-A2-identical HCT recipients. Addressing the question of cross-reactivity of HLA-A2-restricted CMV-specific T cells with minor H antigens in a clinical study would require knowledge of the patient's minor H antigen genotype. However, because of the unbalanced distribution of HLA-A2-restricted minor H antigens in the population and their incomplete identification, this question might be more appropriately evaluated in in vitro experiments than in a clinical study.

Bilateral Sequential NAION: A Comparison of Visual Outcomes in Fellow Eyes Using Quantitative Analysis of Goldmann Visual Fields

Purpose: Previous studies of the visual outcome in bilateral non-arteritic anterior ischemic optic neuropathy (NAION) have yielded conflicting results, specifically regarding congruity between fellow eyes. Prior studies have used measures of acuity and computerized perimetry but none has compared Goldmann visual field outcomes between fellow eyes. In order to better define the concordance of visual loss in this condition, we reviewed our cases of bilateral sequential NAION, including measures of visual acuity, pupillary function and both pattern and severity of visual field loss.Methods: We performed a retrospective chart review of 102 patients with a diagnosis of bilateral sequential NAION. Of the 102 patients, 86 were included in the study for analysis of final visual outcome between the affected eyes. Visual function was assessed using visual acuity, Goldmann visual fields, color vision and RAPD. A quantitative total visual field score and score per quadrant was analyzed for each eye using the numerical Goldmann visual field scoring method previously described by Esterman and colleagues. Based upon these scores, we calculated the total deviation and pattern deviation between fellow eyes and between eyes of different patients. Statistical significance was determined using nonparametric tests.Results: A statistically significant correlation was found between fellow eyes for multiple parameters, including logMAR visual acuity (P = 0.0101), global visual field (P = 0.0001), superior visual field (P = 0.0001), and inferior visual field (P = 0.0001). In addition, the mean deviation of both total (P = 0.0000000007) and pattern (P = 0.000000004) deviation analyses was significantly less between fellow eyes ("intra"-eyes) than between eyes of different patients ("inter"-eyes).Conclusions: Visual function between fellow eyes showed a fair to moderate correlation that was statistically significant. The pattern of vision loss was also more similar in fellow eyes than between eyes of different patients. These results may help allow better prediction of visual outcome for the second eye in patients with NAION. These findings may also be useful for evaluating efficacy of therapeutic interventions.

Magnitude of CD8 T-cell responses against hepatitis C virus and severity of hepatitis do not necessarily determine outcomes in acute hepatitis C virus infection.

Aim: We investigated the relationship between the magnitude of comprehensive hepatitis C virus (HCV)-specific CD8(+) T-cell responses and the clinical course of acute HCV infection. Methods: Six consecutive patients with acute HCV infection were studied. Analysis of HCV-specific CD8(+) T-cell responses was performed using an interferon-gamma-based enzyme-linked immunospot assay using peripheral CD8(+) T-cells, monocytes and 297 20-mer synthetic peptides overlapping by 10 residues and spanning the entire HCV sequence of genotype 1b. Results: Five patients presented detectable HCV-specific CD8(+) T-cell responses against a single and different peptide, whereas 1 patient showed responses against three different peptides. Neither the magnitude of HCV-specific CD8(+) T-cell responses nor the severity of hepatitis predicts the outcome of acute hepatitis. The maximum number of HCV-specific CD8(+) T-cells correlated with maximum serum alanine aminotransferase level during the course (r = 0.841, P = 0.036). Conclusions: HCV-specific CD8(+) T-cell responses were detectable in all 6 patients with acute HCV infection, and 6 novel HCV-specific CTL epitopes were identified. Acute HCV infection can resolve with detectable HCV-specific CD8(+) T-cell responses, but without development of antibody against HCV.

Surgical outcomes of Baerveldt aqueous shunt implantation versus combined phacoemulsification and Baerveldt aqueous shunt implantation

Purpose: To examine the efficacy and safety of Baerveldt shunt (BS) implantation compared to combined phacoemulsification and Baerveldt shunt implantation (PBS). This study was designed to detect a difference in IOP reduction of 20% (~4mmHg) between groups with 90% power. Methods: Sixty patients with medically uncontrolled glaucoma, prospectively underwent either or BS implantation with phacoemulsification (Group PBS; n=30) or BS implantation alone (group BS; n=30, pseudophakic eyes only). Groups were matched for age, glaucoma subtype and length of follow-up. Pre and post-operative measures recorded included patient demographics, visual acuity, IOP, number of glaucoma medications (GMs) and all complications. Success was defined as IOP≤21mmHg and 20% reduction in IOP from baseline with or without GMs. Results: Age of PBS and BS groups was 61 vs 62 years respectively (p=0.72*). There were no significant differences in preoperative baseline characteristics: PBS vs PB, mean IOP =25.5mmHg (standard deviation (SD); ±10.3mmHg) vs 26.1mmHg (SD ±10.6mmHg), p=0.81*; mean GMs=3.0 (SD ±1.1) vs 3.1 (SD ±1.0), p=0.83*; mean VA=0.3 vs 0.3, p=0.89*. At year one there were no significant differences observed between groups in post-operative IOP, GMs or VA, mean IOP =14.1mmHg (SD ±5.4mmHg) vs 11.5 mmHg (SD ±4.2mmHg), p=0.12*; mean GMs=1.6 (SD ±1.4) vs 1.1 (SD ±1.1), p=0.23*; mean VA=0.5 vs 0.4, p=0.46*. Complication rates were similar between the two groups (7% vs 14%). Success rate was lower in eyes with PBS (71%) than with BS (88%), however this did not reach statistical significance (p=0.95, log-rank test). * two-sample t-test Conclusions: There were no significant differences at year one in success or complication rates between PBS and BS groups suggesting that simultaneous phacoemulsification does not have a marked (difference of >4mmHg) effect on tube function. IOP reduction and success were less in the PBS group, a larger sample (n=120) would be required to investigate if there is a 10% difference in IOP reduction between groups, however it is unclear if this would be a clinically significant difference to justify separate surgeries.

Prospective association of the SHARE-operationalized frailty phenotype with adverse health outcomes: evidence from 60+ community-dwelling Europeans living in 11 countries.

BACKGROUND: Among the many definitions of frailty, the frailty phenotype defined by Fried et al. is one of few constructs that has been repeatedly validated: first in the Cardiovascular Health Study (CHS) and subsequently in other large cohorts in the North America. In Europe, the Survey of Health, Aging and Retirement in Europe (SHARE) is a gold mine of individual, economic and health information that can provide insight into better understanding of frailty across diverse population settings. A recent adaptation of the original five CHS-frailty criteria was proposed to make use of SHARE data and measure frailty in the European population. To test the validity of the SHARE operationalized frailty phenotype, this study aims to evaluate its prospective association with adverse health outcomes. METHODS: Data are from 11,015 community-dwelling men and women aged 60+ participating in wave 1 and 2 of the Survey of Health, Aging and Retirement in Europe, a population-based survey. Multivariate logistic regression analyses were used to assess the 2-year follow up effect of SHARE-operationalized frailty phenotype on the incidence of disability (disability-free at baseline) and on worsening disability and morbidity, adjusting for age, sex, income and baseline morbidity and disability. RESULTS: At 2-year follow up, frail individuals were at increased risk for: developing mobility (OR 3.07, 95% CI, 1.02-9.36), IADL (OR 5.52, 95% CI, 3.76-8.10) and BADL (OR 5.13, 95% CI, 3.53-7.44) disability; worsening mobility (OR 2.94, 95% CI, 2.19- 3.93) IADL (OR 4.43, 95% CI, 3.19-6.15) and BADL disability (OR 4.53, 95% CI, 3.14-6.54); and worsening morbidity (OR 1.77, 95% CI, 1.35-2.32). These associations were significant even among the prefrail, but with a lower magnitude of effect. CONCLUSIONS: The SHARE-operationalized frailty phenotype is significantly associated with all tested health outcomes independent of baseline morbidity and disability in community-dwelling men and women aged 60 and older living in Europe. The robustness of results validate the use of this phenotype in the SHARE survey for future research on frailty in Europe.

Protocol for a systematic review on the extent of non-publication of research studies and associated study characteristics.

BACKGROUND: Methodological research has found that non-published studies often have different results than those that are published, a phenomenon known as publication bias. When results are not published, or are published selectively based on the direction or the strength of the findings, healthcare professionals and consumers of healthcare cannot base their decision-making on the full body of current evidence. METHODS: As part of the OPEN project (http://www.open-project.eu) we will conduct a systematic review with the following objectives:1. To determine the proportion and/or rate of non-publication of studies by systematically reviewing methodological research projects that followed up a cohort of studies that a. received research ethics committee (REC) approval,b. were registered in trial registries, orc. were presented as abstracts at conferences.2. To assess the association of study characteristics (for example, direction and/or strength of findings) with likelihood of full publication.To identify reports of relevant methodological research projects we will conduct electronic database searches, check reference lists, and contact experts. Published and unpublished projects will be included. The inclusion criteria are as follows:a. RECs: methodological research projects that examined the subsequent proportion and/or rate of publication of studies that received approval from RECs;b. Trial registries: methodological research projects that examine the subsequent proportion and/or rate of publication of studies registered in trial registries;c. Conference abstracts: methodological research projects that examine the subsequent proportion and/or rate of full publication of studies which were initially presented at conferences as abstracts.Primary outcomes: Proportion/rate of published studies; time to full publication (mean/median; cumulative publication rate by time).Secondary outcomes: Association of study characteristics with full publication.The different questions (a, b, and c) will be investigated separately. Data synthesis will involve a combination of descriptive and statistical summaries of the included methodological research projects. DISCUSSION: Results are expected to be publicly available in mid 2013.