Jesús Almeda

Response to combination antiretroviral therapy: variation by age.

Objective:To provide information on responses to combination antiretroviral therapy in children, adolescents and older HIV-infected persons. Design and setting:Multicohort collaboration of 33 European cohorts. Subjects:Forty-nine thousand nine hundred and twenty-one antiretroviral-naive individuals starting combination antiretroviral therapy from 1998 to 2006. Outcome measures:Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/μl (immunological response) and new AIDS/death were analysed using survival methods. Ten age strata were chosen: less than 2, 2–5, 6–12, 13–17, 18–29, 30–39 (reference group), 40–49, 50–54, 55–59 and 60 years or older; those aged 6 years or more were included in multivariable analyses. Results:The four youngest age groups had 223, 184, 219 and 201 individuals and the three oldest age groups had 2693, 1656 and 1613 individuals. Precombination antiretroviral therapy CD4 cell counts were highest in young children and declined with age. By 12 months, 53.7% (95% confidence interval: 53.2–54.1%) and 59.2% (58.7–59.6%) had experienced a virological and immunological response. The probability of virological response was lower in those aged 6–12 (adjusted hazard ratio: 0.87) and 13–17 (0.78) years, but was higher in those aged 50–54 (1.24), 55–59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults and reduced in those 60 years or older. Those aged 55–59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count. Conclusion:Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy CD4 cell counts, may place this group at increased clinical risk. The poorer virological responses in children may increase the likelihood of emergence of resistance.

Plasmodium falciparum multiple infections in Mozambique, its relation to other malariological indices and to prospective risk of malaria morbidity.

We describe the frequency of Plasmodium falciparum clones infecting individuals living in a rural area of southern Mozambique and analyse the relationship between multiplicity of infection, age and other malariometric indices, including prospective risk of clinical malaria. The genotyping was based on the use of restriction fragment length polymorphism–polymerase chain reaction (RFLP–PCR) analysis of P. falciparum merozoite surface protein 2 (msp2). We analysed 826 samples collected during five cross‐sectional surveys from residents of Manhiça ranging in age from 4 months to 83 years. We also determined the multiplicity of infection in samples obtained from 6‐month‐old infants (n = 79) and children <10 years (n = 158) who were then treated and followed prospectively for 1 year or 75 weeks, respectively. Multiplicity of infection did not vary significantly during the first year of life, but increased thereafter, and decreased during adulthood to the levels found in infants. With increasing multiplicity of infection, there was a statistically significant decrease in the risk of submicroscopic infections. There was also a significant correlation between multiplicity of infection and parasite density in infants, children <4 years of age and adults, suggesting that high densities increase the probability of discriminating more clones in complex infections. We found that the relationship between multiple infections and malaria morbidity is age‐dependent. In infants, the risk of subsequent episodes of clinical malaria was related to the parasite density but not to baseline multiplicity of infection. In older children, however, the more clones a child carried, the more likely they were to have a clinical malaria episode, and this was true after adjusting for parasite densities. This change in the association between multiplicity and risk of clinical malaria may indicate a shift in the host response to P. falciparum.

Malaria in southern Mozambique: Malariometric indicators and malaria case definition in Manhiça district

A total of 2057 children aged <10 years were selected at random from a demographic surveillance system and enrolled in 4 malariometric cross-sectional surveys in different seasons in Manhiça district in southern Mozambique. Plasmodium falciparum accounted for 90% of all malaria infections and the prevalence of asexual P. falciparum ranged from 13.7-21.7% at the end of the dry season to 30.5-34.0% at the end of rainy season. In order to determine the malaria attributable fraction (MAF) of fever, 1021 children from a nearby hospital acted as fever cases and from this separate case-control study the crude MAF was 36%, showing a marked age dependency. Plasmodium falciparum is the most common malaria species in Manhiça. This malaria-mesoendemic area has year-round transmission. The importance of other non-malarial fever-causing conditions among infants was highlighted. Malaria appeared to be a major contributory factor to anaemia in the area.

Ensayo clínico aleatorizado de prevención de caídas y malnutrición en personas de 85 años en la comunidad. Estudio OCTABAIX

INTRODUCTION People aged 85 years old and older constitute a growing population group. Falls and malnutrition are common in the elderly. OBJECTIVE To determine the effectiveness of an individualized multifactorial intervention to reduce falls and malnutrition in community-dwelling persons aged 85 years old. MATERIAL AND METHODS The OCTABAIX study is a randomized controlled clinical trial lasting 3 years in primary care in Costa de Ponent (seven primary care teams). Community-dwelling elders born in 1924 who agreed to participate in the study have been included. Three in-home visits will be made annually by a trained nurse or physician and will be complemented by two biannual analytical studies. Participants will be followed-up for hospitalizations, falls and weight using a monthly calendar. The specifically-designed algorithm to detect risk factors for falls and malnutrition will be used to provide recommendations and specific, standardized interventions for risk reduction in a randomly selected intervention group. Two face-to-face interventions will be carried out and telephone calls will be made to reinforce adherence. The control group will follow routine primary care recommendations. The primary outcome is a decline in the rate of falls and malnutrition. RESULTS The OCTABAIX study aims to reduce the incidence of falls and the risk of malnutrition in the 328 patients included. CONCLUSIONS The OCTABAIX study will help to determine the characteristics of persons aged 85 years old as well as the rate of falls and nutritional risk. The effectiveness of the measures adopted to reduce these geriatric syndromes will also be assessed.

Proposed recommendations for the management of HIV post-exposure prophylaxis after sexual, injecting drug or other exposures in Europe.

Post-exposure prophylaxis (PEP) is the standard of care for a healthcare worker (HCW) accidentally exposed to an HIV infected source person (occupational exposure), but this is not the case for non-occupational exposures. Very few national guidelines exist for the management of non-occupational exposures to HIV in Europe, contrarily to the occupational ones. The administration of non-occupational post-exposure prophylaxis (NONOPEP) for HIV may be justified by: a biological plausibility, the effectiveness of PEP in animal studies and occupational exposures in humans, efficacy in the prevention of mother to child HIV transmission, and cost effectiveness studies. These evidences, the similar risk of HIV transmission for certain non-occupational exposures to occupational ones, and the conflicting information about attitudes and practices among physicians on NONOPEP led to the proposal of these European recommendations. Participant members of the European project on HIV NONOPEP, funded by the European Commission, and acknowledged as experts in bloodborne pathogen transmission and prevention, met from December 2000 to December 2002 at three formal meetings and a two day workshop for a literature review on risk exposure assessment and the development of the European recommendations for the management of HIV NONOPEP. NONOPEP is recommended in unprotected receptive anal sex and needle or syringe exchange when the source person is known as HIV positive or from a population group with high HIV prevalence. Any combination of drugs available for HIV infected patients can be used as PEP and the simplest and least toxic regimens are to be preferred. PEP should be given within 72 hours from the time of exposure, starting as early as possible and lasting four weeks. All patients should receive medical evaluation including HIV antibody tests, drug toxicity monitoring and counseling periodically for at least 6 months after the exposure. NONOPEP seems to be a both feasible and frequent clinical practice in Europe. Recommendations for its management have been achieved by consensus, but some remain controversial, and they should be updated periodically. NONOPEP should never be considered as a primary prevention strategy and the final decision for prescription must be made on the basis of the patient-physician relationship. Finally, a surveillance system for these cases will be useful to monitor NONOPEP practices in Europe.

Clinical evaluation of an in-house IS6110 polymerase chain reaction for diagnosis of tuberculosis

Abstract The aim of this study was to clinically validate a heminested polymerase chain reaction (PCR) method, based on the IS6110 insertion segment of Mycobacterium tuberculosis complex, for the diagnosis of tuberculosis. Samples of pulmonary, extrapulmonary and blood origin were collected prospectively from 331 patients. All samples were processed to detect acid-fast bacilli by direct stain, culture and PCR. The gold standard comparison was a clinically based final case definition of tuberculosis corresponding to group 3 of the American Thoracic Societys classification system. The sensitivities of stain, culture and PCR were 41%, 65% and 59%, respectively. Overall specificity exceeded 97% for all techniques. The combination of PCR and direct stain achieved a sensitivity similar to that of culture alone. The PCR method detected 74 of 95 (78%) culture-positive results. In a hospital setting, PCR could be a useful, reliable tool for diagnosis of tuberculosis and may be introduced as a complementary routine diagnostic laboratory method.

Calidad de vida en nonagenarios: género, funcionalidad y riesgo nutricional como factores asociados

BACKGROUND AND OBJECTIVES The group of age showing a faster growth is the most elderly people. The objective of this study is to describe the health related quality of life in elderly subjects older than 89 year and to identify related factors. PATIENTS AND METHODS A cross-sectional study was done at the third year of a longitudinal study (NonaSantfeliu). We evaluated all survived patients who scored >19 in the Spanish version of the Mental State Examination (MEC). Sociodemographic data were collected, functional status was determined by Lawton-Brody and Barthel Index (BI) and cognition with MEC. Charlson score was used to measure comorbidity and the nutritional risk was evaluated by the short version of Mini Nutritional Assessment questionnaire (short-MNA). Euroqol-5D (EQ-5D) was used to assess health related quality of life. RESULTS The final sample was composed by 37 subjects, 25 women (68%) and 12 men, with a mean age of 94.32 (2.9) years. The mean score in EQ-5D was 0,51 (0,2) and the mean visual analogue self-rating scale (EQ-VAS) was 63 (2,9). Three variables: female gender (p=0,011; regression Beta coefficient : 18,99; IC 95%: 4,66-33,33 , poor BI score (p=0.010; regression Beta coefficient 0.38; IC 95%: 0.09-0.67) and high nutritional risk in short-MNA (p=0.001; regression Beta coefficient: 3.95; IC 95%: 2.50-5.41) were associated with quality of life in the multivariate analyses. CONCLUSION A good health quality of life in the oldest old people was observed in this study. Gender, functional status and nutritional risk were associated with quality of life in nonagenarians.

Physicians’ and patients’ adherence to antiretroviral prophylaxis after sexual exposure to HIV: results from South-Eastern France

Abstract French national guidelines for the management of HIV non-occupational post-exposure (nPEP) were issued in 1998 and updated in 2003. NPEP is available and free of charge in all emergency or AIDS care units of French hospitals. A regional survey was carried out to study physicians’ adherence to national guidelines, and determinants of adherence to nPEP follow-up in individuals sexually exposed to HIV. The survey was based on retrospective data collection of all consultations for nPEP made in the three AIDS information centers in South-Eastern France (January 2001–December 2002). Information included personal data, type of exposure, and treatment at the first visit after exposure and during follow-up. Exposures were classified into high risk (treatment highly recommended), moderate risk (treatment possibly recommended) and negligible risk (treatment never recommended) categories, according to the level of HIV risk of sexual transmission as indicated by the French national nPEP guidelines. Among the 910 sexual exposures, 56%, 37%, and 4% were classified as cases with high, moderate, and no risk respectively. NPEP was prescribed to 85% of cases. HIV risk of sexual exposure was significantly associated with nPEP receipt though more than half of the cases with negligible risk received nPEP. Independent characteristics associated with non-adherence to nPEP follow-up were younger age, being referred to hospital by a physician, sexual exposure with a casual partner or sexual assault, and “moderate risk” exposure. Better information should be provided to physicians prescribing nPEP to limit over-prescription while new strategies should be implemented to improve follow-up of individuals receiving nPEP, especially those who are younger or survivors of sexual assault.

Evaluation of a combined strategy directed towards health-care professionals and patients with chronic obstructive pulmonary disease (COPD): information and health education feedback for improving clinical monitoring and quality-of-life.

BackgroundChronic obstructive pulmonary disease (COPD) is a health problem that is becoming increasingly attended-to in Primary Care (PC). However, there is a scarcity of health-care programs and studies exploring the implementation of Clinical Practice Guidelines (CPG). The principal objective of the present study is to evaluate the effectiveness of a combined strategy directed towards health-care professionals and patients to improve the grade of clinical control and the quality-of-life (QoL) of the patients via a feedback on their state-of-health. A training plan for the health-care professionals is based on CPG and health education.Method/DesignMulti-centred, before-after, quasi experimental, prospective study involving an intervention group and a control group of individuals followed-up for 12 months. The patients receive attention from urban and semi-urban Primary Care Centres (PCC) within the administrative area of the Costa de Ponent (near Barcelona). All the pacients corresponding to the PCC of one sub-area were assigned to the intervention group and patients from the rest of sub-areas to the group control. The intervention includes providing data to the health-care professionals (clinician/nurse) derived from a clinical history and an interview. A course of training focused on aspects of CPG, motivational interview and health education (tobacco, inhalers, diet, physical exercise, physiotherapy). The sample random includes a total of 801 patients (≥ 40 years of age), recorded as having COPD, receiving attention in the PCC or at home, who have had at least one clinical visit, and who provided written informed consent to participation in the study. Data collected include socio-demographic characteristics, drug treatment, exacerbations and hospital admissions, evaluation of inhaler use, tobacco consumption and life-style and health-care resources consumed. The main endpoints are dyspnoea, according to the modified scale of the Medical Research Council (MRC) and the QoL, evaluated with the St Georges Respiratory Questionnaire (SGRQ). The variables are obtained at the start and the end of the intervention. Information from follow-up visits focuses on the changes in life-style activities of the patient.DiscussionThis study is conducted with the objective of generating evidence that shows that implementation of awareness programs directed towards health-care professionals as well as patients in the context of PC can produce an increase in the QoL and a decrease in the disease exacerbation, compared to standard clinical practice.Trial RegistrationClinical Trials.gov Identifier: NCT00922545;

Missed opportunities for HIV testing of patients diagnosed with an indicator condition in primary care in Catalonia, Spain

Objective To estimate the prevalence of HIV testing among patients diagnosed with an indicator condition (IC) for HIV, seen in primary care (PC) in Catalonia, and to estimate the prevalence of HIV infection among those patients. Design Cross-sectional and population-based study in patients aged between 16 and 65 diagnosed with an IC within PC in Catalonia. Methods Data used in this study were extracted from a large population-based public health database in Spain, the Information System for the Development of Research in Primary Care (SIDIAP). All participants registered in SIDIAP from 1 January 2010 to 31 August 2012 and with a diagnosis of an IC were screened to identify those with an HIV test within the following 4 months. Results 99 426 patients were diagnosed with an IC during the study period. In these patients, there were 102 647 episodes in which at least one IC was diagnosed. An HIV test was performed within 4 months in only 18 515 of the episodes in which an IC was diagnosed (18.5%). The prevalence of HIV infection was 1.46%. Women (OR 1.35, 95% CI 1.30 to 1.39), people aged 50 or over (OR 2.85, 95% CI 2.69 to 3.00) and patients having a single IC (OR 3.59. 95% CI 3.20 to 4.03) had the greatest odds of not having an HIV test. Conclusions The study highlights the persistence of missed opportunities for HIV testing within PC in Catalonia. Urgent engagement with PC professionals is required in order to increase HIV testing and prevent late HIV diagnoses.