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Objetivos: Describir la técnica utilizada para imputar la fecha de seroconversión al virus de la inmunodeficiencia humana (VIH) en cohortes de hemofílicos y validar su utilización en sujetos con fecha de seroconversión datada dentro de un intervalo de las cohortes del proyecto GEMES (Grupo Español Multicéntrico para el Estudio de Seroconvertores al VIH). Método: Se dispone de 632 hemofílicos procedentes de tres unidades de hemofilia identificados como VIH+ entre 1983 y 1985 (fechas de las primeras pruebas VIH+) y 1.092 individuos procedentes de 5 cohortes del proyecto GEMES con una ventana de seroconversión (tiempo entre pruebas VIH- y VIH+) menor de 3 años en los que se asume el punto medio (PM) como fecha de seroconversión. Se imputa la fecha de seroconversión para los dos grupos a partir de la estimación de la distribución de probabilidad de seroconversión que se obtiene mediante el algoritmo EM. Se utilizan dos métodos de imputación: uno a partir del valor esperado de la distribución estimada y otro de la media geométrica de 5 muestras aleatorias de la distribución estimada. Las imputaciones se han validado en las cohortes de no hemofílicos al comparar con el PM y el tiempo libre de sida y la supervivencia con las diferentes estimaciones de seroconversión. Resultados: La mediana de la seroconversión se sitúa en mayo de 1993 para los no hemofílicos y en 1982 para los hemofílicos. En las cohortes de no hemofílicos no se observan grandes diferencias entre las fechas de la seroconversión estimada como el punto medio y las medianas estimadas a partir de los dos métodos de imputación. Lo mismo ocurre en el caso de las cohortes de hemofílicos. No se observan diferencias en las estimaciones del tiempo libre de sida y supervivencia en ambos grupos de cohortes. Conclusiones: La imputación de la media geométrica de varias muestras aleatorias y la imputación de valor esperado proporcionan una buena estimación de la fecha de seroconversión frente al VIH que puede ser utilizada para estimar el tiempo libre de sida y la supervivencia en una cohorte de hemofílicos para los que se desconoce la fecha de seroconversión

Background: Although the consensus is that gender does not influence HIV progression, its relevance may depend on the setting.Aim: To study gender differences in HIV progression to AIDS and death from 1986 to 2001 in a cohort of injecting drug user (IDU) seroconverters in Spain.Methods: Risk of AIDS and death in persons infected for the same length of time were compared through Kaplan-Meier, allowing for late entry, and Cox regression adjusting for gender, age, and calendar period (before 1992, 1992-1995, 1996-1998, 1999-2001) fitted as time dependent covariates.Results: Of 929 IDU, 24.7% were women. Median seroconversion year was 1993.3 for men and women. 44% of women and 34% of men received antiretroviral therapy. Risk of AIDS was lower in women in univariate (hazard ratio (HR) 0.72; 95%CI:0.51 to 1.01) and multivariate analyses (HR 0.73 95%CI:0.52 to 1.03). A 46% reduction in risk of AIDS for period 1999-2001 compared with 1992-1995 was seen in both men and women (HR: 0.56 (95%CI:0.36 to 0.87). As for mortality, women's risk of death was lower univariately (HR 0.67 95%CI:0.45 to 0.99) although compared with 1992-95, men experienced a 34% reduction in mortality during 1999-2001 (HR 0.66 95%CI:0.40 to 1.01), which was not statistically significant in women.Conclusions: HIV progression was lower in female IDU before and after 1997 and their uptake of antiretroviral therapy was higher than male IDU. The inability to detect a reduction in mortality for women during 1999-2001 is probably attributable to lack of power. Differences in severity of addiction, drug using patterns, and competing cau es of death may explain these findings. [ABSTRACT FROM AUTHOR]

Summary Background A study to evaluate the adherence to and appropriateness of anti-osteoporotic treatments in a cohort of men and women aged 50 and over participating in the ESOSVAL-R study. Methods/Design Design: An observational, longitudinal, prospective cohort study; Study subjects: Men and women aged 50 and over living in the Valencia Region (Spain) who initiated treatment between June 15, 2009, and June 15, 2011, in primary healthcare centers with electronic medical records; Data sources: The main data source will be electronic medical records. Measurement of results: Degree of compliance with and persistence of anti-osteoporotic treatments, and the proportion of patients with appropriate anti-osteoporotic treatment in accordance with the most relevant and high impact recommendations with clearly defined treatment algorithms in Spain (the Spanish National Health System guide (2010), the General Practitioners' Society (2007) and the General Directorate for Pharmacy and Medical Products of Madrid (2007)), and with the National Osteoporosis Foundation (NOF, 2010), and the International Osteoporosis Foundation guidelines (IOF, 2008); Analysis: 1.) Descriptive analysis of patients undergoing treatment and the treatments prescribed; 2.) Descriptive analysis of compliance with and persistence of anti-osteoporotic treatments; 3.) Analysis of factors associated with compliance with and persistence of treatments by Cox proportional hazard regression models, 4.) Descriptive analysis of appropriateness of treatment; 5.) Analysis of factors associated with the appropriateness of treatment by multilevel models (4 levels: patient, doctor, Basic Healthcare Zone/Primary Healthcare Center, and Health Area variables). Discussion ESOSVAL-AD will provide information regarding adherence to osteoporosis treatments and the factors associated with a higher or lower adherence (including the appropriateness of the treatment) in the Spanish context. A better understanding of this phenomenon and the interventions needed to address it would contribute to the increased effectiveness of therapeutic measures, a reduction in morbidity and mortality, and a corresponding reduction in healthcare costs.

Abstract Background Today, while there are effective drugs that reduce the risk of osteoporotic fracture, yet there are no broadly accepted criteria that can be used to estimate risks and decide who should receive treatment. One of the actual priorities of clinical research is to develop a set of simple and readily-available clinical data that can be used in routine clinical practice to identify patients at high risk of bone fracture, and to establish thresholds for therapeutic interventions. Such a tool would have high impact on healthcare policies. The main objective of the ESOSVAL-R is to develop a risk prediction scale of osteoporotic fracture in adult population using data from the Region of Valencia, Spain. Methods/Design Study design: An observational, longitudinal, prospective cohort study, undertaken in the Region of Valencia, with an initial follow-up period of five years; Subjects: 14,500 men and women over the age of 50, residing in the Region and receiving healthcare from centers where the ABUCASIS electronic clinical records system is implanted; Sources of data: The ABUCASIS electronic clinical record system, complemented with hospital morbidity registers, hospital Accidents & Emergency records and the Regional Ministry of Health's mortality register; Measurement of results: Incident osteoporotic fracture (in the hip and/or major osteoporotic fracture) during the study's follow-up period. Independent variables include clinical data and complementary examinations; Analysis: 1) Descriptive analysis of the cohorts' baseline data; 2) Upon completion of the follow-up period, analysis of the strength of association between the risk factors and the incidence of osteoporotic fracture using Cox's proportional hazards model; 3) Development and validation of a model to predict risk of osteoporotic fracture; the validated model will serve to develop a simplified scale that can be used during routine clinical visits. Discussion The ESOSVAL-R study will establish a prediction scale for osteoporotic fracture in Spanish adult population. This scale not only will constitute a useful prognostic tool, but also it will allow identifying intervention thresholds to support treatment decision-making in the Valencia setting, based mainly on the information registered in the electronic clinical records.

The article reports a study that describes changes in mortality rates and distribution of causes of death between 1987 and 2001 among a cohort of intravenous drug users (IDUs). Researchers conducted a cohort study of 6178 IDUs recruited between January 1990 and December 1996 in three AIDS prevention and information centres for voluntary counselling and testing in Valencia, Spain and followed up until November 2001. Researchers obtained sociodemographics, drug using behaviours and HIV status at study entry. Researchers concluded that the overall death rate has decreased since the introduction of highly active anti-retroviral therapy in 1997 in HIV positive patients because of the reduction in AIDS related deaths.

Objective: To compare spinal misalignment and execution time of 3 rescue maneuvers for casualties in traffic accidents., Materials and Methods: Biomechanical analysis using inertial sensors to measure the range of spinal misalignment and execution time of 3 maneuvers: 1) standard manual rescue (SMR); 2) rapid extrication device (RED); 3) extrication device (ED). The sample consisted of 117 rescue professionals (firefighters) from 14 Autonomous Communities in Spain. The total range of motion and the execution time of maneuvers were compared using ANOVA., Results: The highest range of cervical flexion-extension movement was recorded with RED (30° ± 9°). There were no statistically significant differences between SMR (21° ± 9°) and ED (21° ± 10°). In dorsal flexion-extension, the highest range of movement was with RED (36° ± 10°), followed by ED (30° ± 7°), with the lowest found for SMR (26° ± 11°). RED presented the least restriction of cervical (p < 0.001) and dorsal movement (p < 0.001). The quickest maneuver was SMR (average of 55″), followed by RED (average of 92″), with a considerable difference using ED (average of 225″) (p < 0.001)., Conclusion: The standard manual rescue maneuver (SMR) generated the smallest range of spinal movement and also required the shortest execution time., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ANA NICOLAS CARRILLO reports financial support was provided by Spanish Society of Emergency Medicine (SEMES). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To compare the results of two ovarian stimulation protocols for IVF in patients at risk of poor ovarian response: corifollitropin alfa followed by hp-hMG versus daily administration of hp-hMG. We intended to demonstrate the non-inferiority of the protocol with corifollitropin alfa., Study Design: This is a prospective, randomized, non-inferiority, controlled study. We compared two ovarian stimulation protocols for IVF in 234 patients, under 40 years of age and at risk of poor ovarian response. First protocol was a single injection of 150 μg corifollitropin alfa and the second, a daily injection of 300 IU of hp-hMG during the first week of ovarian stimulation. In both groups, if necessary, a daily injection of 300 IU of hp-hMG was dispensed until the criteria for hCG administration are met. For the primary and secondary outcomes, results were analysed by using a one-sided chi-square test or a Fisher exact test, as appropriate, with a level of significance of 0.05. For continuous variables, parametric (independent t-test) or non-parametric (Mann-Whitney test) tests were used depending on the normality of the distribution. Statistical significance was set at P < 0.05., Results: The ongoing pregnancy rate, live birth rate (15.2 vs 20.2) (P = 0.33), and the cumulative live birth rate (15.2 vs 22.0) (P = 0.19) per started cycle did not show significant differences between the corifollitropin alfa and hp-hMG groups, and the difference estimated between treatments was -5% [95% CI: (-15.1, 5.0)]., Conclusions: It was not possible to probe non-inferiority of the protocol with corifollitropin alfa followed by hp-hMG compared to hp-hMG in patients at risk of poor ovarian response undergoing ICSI., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Pharmacological secondary prevention in patients after an acute coronary syndrome (ACS) has contributed substantially to reductions in cardiovascular morbidity and mortality and, overall, has undergone important improvements in recent years. Nevertheless, there is still a considerable adherence gap and opportunity for improvement., Objective: To assess, in a cohort of patients who survived an ACS, adherence to commonly prescribed secondary prevention drugs, factors associated to adherence, and variations among health care delivery areas., Methods: We combined the medical and pharmacy databases from a regional public health service in Valencia, Spain, to construct a population-based cohort of patients discharged alive after an emergency admission for an ACS to any hospital of the Valencia Health Agency in 2008. We evaluated medication adherence by determining the proportion of days covered (PDC) for each therapeutic group (antiplatelet agents, beta-blockers, angiotensin antagonists, and statins) in the 9 months following hospital discharge. Fully adherent patients were defined as those having enough treatment to cover 75% (PDC75) of the follow-up period., Results: The study cohort consisted of 7,462 patients. PDC75 was reached by 69.9% of patients taking antiplatelet agents, 43.3% taking beta-blockers, 45.4% taking angiotensin antagonists, and 58.8% taking statins. Approximately 18% of patients did not reach PDC75 with any treatment, while 47.6% did so for 3 or more therapeutic groups. Lower adherence was found in diagnoses other than myocardial infarction. Other factors associated with nonadherence were older age, women, having copayment, foreign born, and most comorbidities (except for hypertension and hyperlipidemia, which were inversely associated, and diabetes and peripheral disease, which were not significantly associated). Health care delivery areas showed certain variability in their performance on these adherence measures that remained after the adjustment for covariates, although confidence intervals overlapped except between areas at the extremes., Conclusions: The proportion of fully adherent patients remains suboptimal, and important improvements are still possible in secondary prevention of ischemic heart disease. The combination of electronic health information systems may be very useful for monitoring adherence and evaluating the effectiveness of adherence and other quality improvement interventions.

Objectives: To explore the utility of combining health information systems from the Valencia Health Agency to characterize folate supplementation in pregnant women in the autonomous region of Valencia (Spain)., Methods: The cohort comprised women who gave birth during 2009 in hospitals within the Valencian Health Agency. These women were retrospectively followed-up using ABUCASIS electronic medical records and the GAIA electronic prescription system to identify folate consumption in the 3 months before and after conception., Results: In 2009, there were 38,069 births in hospitals of the Valencian Health Agency, of which 37,040 (97.3%) were included for analysis. In 34% of women, at least one folate dispensation was registered with an official prescription form within the periconceptional period (6.6% in the 3 months prior to conception). Dispensation with an official prescription form was associated with older women, free pharmaceutical prescriptions, birth in Spain, antiepileptic medications, and a diagnosis of diabetes. Eight percent of women (23.6% of the folate-treated women) received folates at high doses., Conclusions: Folate consumption during pregnancy is systematically under-registered by healthcare information systems because health professionals do not use the official prescription form for prescription and dispensation. Database linkage is an inadequate approach to assess folic acid supplementation during pregnancy., (Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.)

INTRODUCTION. Traumatic brain injuries (TBI) are a major cause of morbidity and mortality in children and adolescents but there are hardly any studies on the incidence and temporal evolution. AIM. To describe recent trends (2002-2009) in the incidence of hospitalization for TBI in children and adolescents in the region of Valencia. PATIENTS AND METHODS. Emergency admissions were identified in hospitals in the Valencian Health Agency from patients aged 0-19 years with a diagnosis of TBI (codes of the International Classification of Diseases 800, 801, 803, 804 and 850 to 854) during 2002 to 2009. The severity was classified using the fifth digit of these codes and the crude and standardized rates per 100,000 children were estimated stratified by age, sex and severity. RESULTS. From 2002 to 2009 a total of 5,504 TBI in children up to age of 19 years were hospitalized (mild: 92.9%; moderate to severe: 7.1%). In-hospital mortality was 0.6% for mild TBI and 15.7% for moderate-severe. Crude rates of mild head injury per 100,000 children fell from 85.9 to 55.4 in 2002-2009 (boys: 114.1 to 68.3, girls: 56.1 to 41.8), especially in the 15-19 years. For moderate-severe TBI, rates decreased from 5.73 to 2.78 per 100,000 in 2002-2009 (boys: 8.69 to 3.67; girls: 2.59 to 1.84). CONCLUSIONS. The incidence of pediatric TBI in the Valencia region has decreased significantly in the period 2002-2009, but their medical, legal, societal and family consequences still represents a substantial burden.

Objectives: To analyse the effect of educational level on the progression from HIV seroconversion to highly active antiretroviral therapy (HAART) requirement, HAART initiation, AIDS and death from any cause at different periods of the HIV epidemic in Spain., Methods: Open, prospective, multicentre cohort of HIV seroconverters set up in 1983. The risk of progression was calculated by the multiple decrements method. Effect of educational level was estimated by Fine and Gray model, adjusting for sex, HIV transmission category, age and method to estimate seroconversion. Calendar period was introduced as a variable that could change over time (<1997; 1997-2003; >2003)., Results: Up to 2009, 989 HIV seroconverters with information on educational level were identified. Some 52% and 48% had a low and a high educational level respectively. Persons with higher education had 32% lower risk of death (HR: 0.68; 95% CI 0.45 to 1.03). Regarding progression to AIDS, educational level had no effect in the pre-HAART era (HR: 1.47; 95% CI 0.91 to 2.38), but did show an effect in the period 1997-2003 (HR: 0.58; 95% CI 0.34 to 0.99), which was accentuated after 2004 (HR: 0.26; 95% CI 0.10 to 0.68). No difference was found in time to HAART requirement or initiation., Conclusions: Results suggest that, despite similar access to HAART, persons with low educational level are at increased risk of HIV disease progression, highlighting the impact of social inequities on health. The availability of more effective treatments over time will strengthen the protective effect of higher education on the development of AIDS.

Introduction: Several observational studies support the protective effect of combined antiretroviral therapy (cART) on time to first AIDS-defining event, but the effect on multiple AIDS defining illnesses remains unclear.The aim of this study is to analyse whether the protective effect of cART persists beyond the first AIDS-defining illness., Material and Methods: A total of 1938 subjects from GEMES seroconverter cohort have been included. To analyse cART effectiveness, calendar time has been divided into three periods according to antiretroviral availability. A population-averaged proportional hazard model with staggered entries that counted the gap time, and had event-specific baseline risks, was fitted., Results: During follow-up, 1524 (78.6%), 259 (13.4%), 83 (4.3%) and 72 (3.7%) subjects incurred 0, 1, 2, and 3 or more AIDS-defining illnesses, respectively. After adjustment for sex, age at seroconversion and exposure category, the Relative Risk (RR) of AIDS in the cART period was 0.38 (95%CI 0.30-0.48) compared with the 1992-95 period. The RR of the first, second and third AIDS-defining illness in the cART period were 0.40 (95% CI: 0.32-0.50), 0.27 (95% CI: 0.15-0.50) and 0.41 (95% CI: 0.18-0.96) respectively, relative to the reference calendar period when we allowed the odds ratios to vary by the number of prior AIDS-defining events. The relative risk of AIDS, taking all events into account, was 0.32 (95% CI: 0.25-0.40). Intravenous drug users have a higher risk of developing a first episode of AIDS than homosexuals, RR: 2.14 (95% CI: 1.48-3.10)., Conclusions: Results indicate that the relative effect of cART appears to be both protective and stable over multiple AIDS-defining illnesses. Analysis of multiple AIDS-defining illnesses improves the precision of the estimated relative risk., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Objective: To analyze whether the effectiveness of combined antiretroviral therapy in delaying progression to AIDS and death is affected by social inequities in a cohort of HIV-positive injecting drug users (IDUs)., Methods: A cohort of 3,122 HIV-positive IDUs identified in the AIDS Information and Prevention Centers of the autonomous region of Valencia was analyzed, with further follow-up in 1,876. Progression to AIDS and death after seroconversion were calculated by Kaplan-Meier estimation according to sociodemographic variables (age, sex, education, marital status, length of addiction). Cox regression models were also fitted., Results: No significant differences were observed according to the variables considered when analyzing time to AIDS development. Evaluation of survival time revealed that individuals with further follow-up showed an excess of mortality (HR = 1.35; 95%CI: 0.20-1.54). For individuals without follow-up, mortality risk was reduced in those with secondary school education (HR = 0.51; 95%CI: 0.35-0.74) and with university education (HR = 0.41; 95%CI: 0.18-0.93) compared with those with no education. When individuals with follow-up were analyzed, the differences lost significance for those with secondary school education (HR = 0.92; 95%CI: 0.72-1.19) and university education (HR = 0.62; 95%CI: 0.35-1.11)., Conclusions: The mortality excess found in IDUs with lower educational levels, especially among those not seeking healthcare in the initial period after being identified as HIV-positive, highlights the need for interventions aimed at facilitating access to health systems, especially among the socially disadvantaged.

Aims: To monitor changes in cause-specific mortality before and after 1997 according to human immunodeficiency virus (HIV) serological status in a cohort of injecting drug users (IDUs) observed for a 17-year period (1987--2004)., Design: Community-based prospective cohort study of IDUs recruited in three acquired immunodeficiency virus (AIDS) prevention centres (1987--96) and followed-up until to 2004., Methods: We obtained annual overall mortality rates and mortality rates by specific causes according to HIV status. Poisson regression models were adjusted to compare mortality rates between calendar periods. Significant changes in slope trends were evaluated by join-point regression. Disease-specific mortality rates were estimated using competing risk models., Findings: From 7186 IDUs recruited (80677.218 person-years), 1589 deaths were observed with an overall mortality rate of 19.7 per 1000 person-years (95% CI, 18.8-20.7). This rate decreased from 22.9 per 1000 (95% CI, 21.4-24.7) before 1997 to 17.4 per 1000 (95% CI, 16.3-18.6) after 1997 [relative risk (RR) 0.83; 95% confidence interval (CI), 0.75-0.92]. Risk of death for HIV-positive was four times higher than for HIV-negative (RR 4.08; 95% CI, 3.63-4.58). Among HIV-positive individuals a significantly decreased change point in trend was found in 1997 for both total and AIDS mortality. HIV-negative individuals showed a similar pattern for drug overdose, suicide and accident mortality. Both groups showed an increase in proportional mortality by liver-related causes, cardiovascular diseases and cancer. Furthermore, a progressively increasing trend was observed for the three causes. However, there were no significant differences according to serological groups., Conclusions: Cardiovascular and cancer mortality are increasing among IDUs, but the increases are not related to HIV infection. We have not found a link between highly active antiretroviral therapy (HAART) introduction and increases in mortality for specific causes.

Objective: To analyse incidence and determinants of tuberculosis in HIV-seroconverters before and after the introduction of HAART., Methods: Data from a multicenter cohort study of 2238 HIV-seroconverters between the 1980s and 2004 were analysed and censored by December 2004. Calendar year at risk intervals were pre-1992, 1992-1996 and 1997-2004. Incident tuberculosis was calculated as cases per 1000 person-years (p-y). Survival analyses using Kaplan-Meier and multivariate Cox regression allowing for late-entry were used. Proportional hazards assumptions were checked with tests based on Schoenfeld residuals., Results: Overall, 173 (7.7%) patients developed tuberculosis over 23 698 p-y at a rate of 7.3 cases per 1000 p-y [95% confidence interval (CI), 6.3-8.5]. Incident tuberculosis was higher in intravenous drug-users (IDUs), 12.3 per 1000 p-y compared with persons infected sexually, 3.8 per 1000 p-y (P < 0.001), and persons with clotting disorders (PCD), 2.7 per 1000 p-y (P < 0.001). A decreasing tuberculosis incidence trend was observed from 1995 in all categories. Highest tuberculosis rates, 44 per 1000 p-y, were observed prior to 1997 in IDUs infected with HIV for 11 years. In multivariable analyses women were less likely to develop tuberculosis [relative hazard (RH), 0.62; 95% CI, 0.41-0.96; P < 0.05) and IDUs were more likely to develop tuberculosis (RH, 3.0; 95% CI, 1.72-5.26, P < 0.001). In the HAART era, the hazard of developing tuberculosis was 70% lower (RH, 0.31; 95% CI, 0.17-0.54; P < 0.001). Before 1997, the risk of tuberculosis increased with time since HIV seroconversion, whereas it remained nearly constant in the HAART era., Conclusions: Since the mid-1990s important decreases in tuberculosis have been observed in HIV-seroconverters that probably reflect the impact of both HAART and tuberculosis control programmes.

Objectives: Standard methods to evaluate population effectiveness of treatments in observational studies have important limitations to appropriately adjust for time-dependent confounders. In this paper, we describe a recently developed methodological approach, marginal structural models (MSM), and use it to estimate the effectiveness of highly active antiretroviral therapy (HAART) on AIDS or death incidence., Subjects and Methods: We analyzed all subjects followed after 1997 as part of the GEMES project (comprised by several cohorts of HIV seroconverters in Spain) and who had not used HAART before the start of follow-up. To estimate the effect of HAART on AIDS or death incidence, we estimated the parameters of a marginal structural Cox model by fitting an inverse probability weighted logistic regression model. The estimation of the weights was based on CD4 count, time since seroconversion, sex, age, transmission category and previous treatment., Results: 917 eligible subjects were followed for an average of 3.4 years and we observed 139 events. 42.1% of the participants received HAART during the study. The estimated rate ratio was 1.01 (95% confidence interval [CI], 0.68-1.49) using a Cox model without covariates and 0.90 (95% CI, 0.61-1.32) using a Cox model with time-dependent covariates. The causal rate ratio estimated for MSM was 0.74, (95% CI, 0.49-1.12)., Conclusions: The beneficial effect of HAART estimated by the MSM, but largely missed by conventional methods, is consistent with the findings of previous randomized studies. The MSM appropriately adjusted for the time-dependent covariate CD4 count, which is both a time-varying confounder and is affected by prior treatment.

Objective: To study trends in progression to AIDS, all-cause mortality, and cause-specific mortality (AIDS-related, liver disease, and hemorrhagic complications) over calendar periods with different exposure to highly active antiretroviral therapy (HAART) in a cohort of hemophiliacs in Spain, taking into account the competing risks of the causes of death., Methods: Multicenter cohort of HIV-infected hemophiliacs. HIV seroconversion was estimated using mathematic techniques for interval-censored data from 1979 through 1985. Rates of AIDS and cause-specific death were calculated by Poisson regression, allowing for late entry, for the periods 1985 through 1992, 1993 through 1996, 1997 through 2000 (early HAART), and 2001 through 2003 (late HAART), also allowing for competing risks., Results: Of 585 subjects, 44% were younger than 15 years of age, 82% had severe hemophilia, 86% had type A hemophilia, and the median seroconversion date was October 1982. Calendar period and age at HIV seroconversion strongly influenced AIDS and death rates. Compared with 1993 through 1996, decreases of 75% (relative risk [RR] = 0.25, 95% confidence interval [CI]: 0.14 to 0.43) and 72% (RR = 0.28, 95% CI: 0.12 to 0.63) in the RR of AIDS were observed in early and late HAART. For all-cause mortality, 72% (RR = 0.28, 95% CI: 0.18 to 0.42) and 83% (RR = 0.17, 95% CI: 0.09 to 0.33) decreases were observed by 1997 through 2000 and 2001 through 2003. For liver-related deaths, increases were observed in the late-HAART period (RR = 2.80, 95% CI: 0.94 to 8.36) compared with 1993 through 1996, but using competing risks, this RR was substantially reduced (RR = 1.70, 95% CI: 0.57 to 5.04)., Discussion: Major reductions in AIDS and death rates were observed from 1997 to 2003 in hemophiliacs. These survival improvements are largely attributable to decreases in AIDS-related deaths and have been accompanied by increases in liver disease death rates, which are overestimated if competing risks are not taken into account.

Progression to AIDS and death for 1129 HIV seroconverters from the GEMES cohort were analysed by calendar period (1996-1997, 1998-1999, 2000 onwards). A further hazard reduction was observed for a later period for both. Intravenous drug users (IDU) had a faster progression. The results highlighted the importance of monitoring the effectiveness of highly active antiretroviral therapy and to improve public health strategies directed to IDU to reduce inequity in HIV infection care.

Objective: To assess the impact of HIV and hepatitis C virus (HCV) infection on long-term mortality in injecting drug users (IDU)., Design: Community-based prospective cohort study., Methods: Mortality data from follow-up in clinical sites and the Mortality Registry by December 2002 were collected for 3247 IDU who attended three centres for voluntary counselling and testing for HIV/AIDS, HCV and hepatitis B virus (HBV) in 1990-1996. Mortality rates by Poisson regression were adjusting for age, sex, duration of drug use, education, HBV and calendar period (1990-1997 and 1998-2002)., Results: Overall, 11.2% were HIV/HCV negative, 43.7% positive only for HCV and 45.1% positive for both. During 26 772 person-years of follow-up, 585 deaths were detected (2.19/100 person-years). Before 1997, HIV/HCV-positive subjects had a five-fold increase in risk of death [relative risk (RR), 5.4; 95% confidence interval (CI), 2.5-11.4] compared with those negative for both; after 1997, a three-fold increase was observed (RR, 2.7; 95% CI, 1.7-4.2). Being HCV positive/HIV negative was not associated with an increase in the risk of death either before (RR, 1.3; 95% CI, 0.6-2.9) or after (RR, 1.2; 95% CI, 0.8-1.9) 1997 compared with HCV/HIV negative. While increases in mortality were seen in those HCV/HIV negative (RR, 1.6; 95% CI, 0.7-3.7) and those only positive for HCV (RR, 1.5; 95% CI, 1.0-2.1), a 20% reduction among coinfected IDUs was observed after 1997 (interaction P = 0.033)., Conclusions: HCV/HIV coinfection has had a large impact on mortality in IDU. After 1997, mortality increased in HIV negative/HCV positive subjects and decreased in HIV positive/HCV positive.

Background: In cohort or longitudinal studies, subjects are recruited some time after the beginning of the problem, as in HIV infection. The aim of this paper is to show several imputation techniques of the beginning of follow up and evaluate its use in the framework of a study of HIV progression., Methods: Three subcohorts of HIV+ subjects recruited in Valencia and Castellón CIPS up to 1996 are available. Seroconversion date was estimated for 244 Seroincidents, 887 seroprevalents with CD4 measurements and 337 without CD4 measurements. For seroincidents midpoint between last HIV- and first HIV+ visits was considered. For prevalent with CD4 serocon version date was imputed from 5 random samples of a progression model of infection to a CD4 level. For prevalent without CD4 seroconversion date was imputed from 5 random samples of HIV incidence density obtained from the other subcohorts. The imputation was repeated 500 times, assigning the seroconversion date as the median of imputations and obtaining confidence limits from 5 and 95 percentiles. Imputation validity was tested comparing time to AIDS and death for each one of the 3 groups., Results: 443 and 405 deaths were observed among the 1468 subjects. Median of seroconversion was January 1993 for incidents, January 1991 for prevalents with CD4 and November 1988 for prevalents without CD4. The latest group showed a worse survival and AIDS free time compared to the other two cohorts., Conclusions: The imputation tools used showed their usefulness to reduce the survival bias in observational studies. Their generalization depends on the viability of incident cohorts, the availability of a progression marker or a origin on time.

Objectives: To describe the methods used to impute HIV seroconversion date in the haemophiliac cohorts from GEMES project and to validate its use., Method: 632 haemophiliacs coming from three hemophilia units identified as HIV+ and 1.092 individuals coming from 5 project GEMES cohorts with a seroconversion window (time among test HIV and HIV+) less than 3 years where mid point (PM) was assumed as seroconversion date. For both groups, seroconversion date was imputed after estimating the probability distribution of seroconversion by means of the EM algorithm. Two imputation methods are used: one obtained from the expected value and the other from the geometric mean of 5 random samples. from the estimated distribution. Imputations have been validated in the non haemophiliacs cohorts comparing with the PM seroconversion date. Also AIDS free time and survival from the different seroconversion imputed dates were compared., Results: Median seroconversion date is located in May of 1993 for the non haemophiliacs and in 1982 for the haemophiliacs. Not big differences are observed among the imputed seroconversion dates and the mid-point seroconversion date in the non-haemophiliac cohorts. Similar results are found for the haemophiliac cohorts. Also no differences are observed in the estimated AIDS-free time for both groups of cohorts., Conclusions: Geometric mean imputation from several random samples provides a good estimate of the HIV seroconversion date that can be used to estimate AIDS-free time and survival in haemophiliac cohorts where seroconversion date is ignored.