Assessment of an outreach street-based HIV rapid testing programme as a strategy to promote early diagnosis: a comparison with two surveillance systems in Spain, 2008-2011.

We assess the added value of a multisite, street-based HIV rapid testing programme by comparing its results to pre-existing services and assessing its potential to reduce ongoing transmission. Between 2008 and 2011, 8,923 individuals underwent testing. We compare outcomes with those of a network of 20 sexually transmitted infections (STI)/HIV clinics (EPI-VIH) and the Spanish National HIV Surveillance System (SNHSS); evaluate whether good visibility prompts testing and assess whether it reaches under-tested populations. 89.2% of the new infections were in men who have sex with men (MSM) vs 78.0% in EPI-VIH and 56.0% in SNHSS. 83.6% of the MSM were linked to care and 20.9% had <350 CD4 HIV prevalence was substantially lower than in EPI-VIH. 56.5% of the HIV-positive MSM tested because they happened to see the programme, 18.4% were previously untested and 26.3% had their last test ≥2 years ago. The programme provided linkage to care and early diagnosis mainly to MSM but attendees presented a lower HIV prevalence than EPI-VIH. From a cost perspective it would benefit from being implemented in locations highly frequented by MSM. Conversely, its good visibility led to reduced periods of undiagnosed infection in a high proportion of MSM who were not testing with the recommended frequency.

Quality of life in a community sample of young cocaine and/or heroin users: the role of mental disorders.

PURPOSE: Drug addiction and psychiatric disorders are frequently concomitant; however, few studies have investigated the impact of psychiatric disorders other than substance use disorder (SUD) on health-related quality of life (HRQoL) in drug users not in treatment. We studied the association of psychiatric disorders other than SUD with HRQoL in a street-recruited sample of cocaine and/or heroin users. METHODS: It is a cross-sectional study involving 287 young users of cocaine and/or heroin in Barcelona, Spain. HRQoL was assessed with the Nottingham health profile (NHP). Patterns of drug use and mental disorders were assessed using the Spanish version of the psychiatric research interview for substance and mental disorders IV, and degree of dependence through the severity of dependence scale (SDS). The association of mental disorders with HRQoL was assessed through a Tobit regression analysis. RESULTS: The overall NHP score was 23.9 (SD = 20.5, range 0-91.7). Sixty-one percent of the sample had two or more SUDs; 22 % had at least one non-SUD Axis I disorder (anxiety, mood, psychotic, or eating disorder); and 27.2 % had a borderline personality disorder (BPD) and/or antisocial personality disorder. Variables negatively associated with the global NHP score were psychosis [transformed beta coefficient: 15.23; 95 % confidence interval [CI] 4.48-25.97], BPD (9.55; 95 % CI 2.95-16.15), severity of dependence (8.12; 95 % CI 3.37-12.87), having two or more SUDs (for two or three SUDs: 6.83; 95 % CI 2.08-11.59) (>3 SUDs: 7.70; 95 % CI 1.72-13.68) and the intravenous use of some substance (10.20; 95 % CI 6.00-14.40). CONCLUSION: HRQoL among street-recruited illegal substance users was impaired, particularly among those with psychiatric comorbidity, psychosis, and BPD being especially relevant.

Cocaine use and risk of stroke: a systematic review.

BACKGROUND: Both cocaine use and strokes impact public health. Cocaine is a putative cause of strokes, but no systematic review of the scientific evidence has been published. METHODS: All relevant bibliographic-databases were searched until January 2014 for articles on the epidemiological association between cocaine use and strokes. Search strings were supervised by expert librarians. Three researchers independently reviewed studies for inclusion and data extraction following STROBE recommendations. Quality appraisal included study validity and bias. Both ischemic and hemorrhagic strokes were considered. RESULTS: Of 996 articles, 9 were selected: 7 case-control studies (CCS) and 2 cross-sectional (CSS) studies. One CCS (aOR=6.1; 95% CI: 3.3-11.8) and one CSS (aOR=2.33; 95% CI: 1.74-3.11) showed an association between cocaine and hemorrhagic strokes. The latter study also found a positive relationship with ischemic stroke (aOR=2.03; 95% CI: 1.48-2.79). Another CCS found the exposure to be associated with stroke without distinguishing between types (aOR=13.9; 95% CI: 2.8-69.4). One forensic CCS found that deaths with cocaine-positive toxicology presented a 14.3-fold (95% CI: 5.6-37) and 4.6-fold (95% CI: 2.5-8.5) increased risk of atherosclerosis compared to opioid-related deaths and hanging-deaths respectively. One CCS did not provide an aOR but found a statistically significant association between cocaine and hemorrhagic stroke. Three CCS and one CSS did not find any relationship between cocaine and strokes. Inadequate control for confounding was not uncommon. CONCLUSIONS: Epidemiological evidence suggests that cocaine use increases the risk of stroke. Larger, more rigorous observational studies, including cohort approaches, are needed to better quantify this risk, and should consider stroke type, hypertension variation, frequency/length of cocaine use, amphetamines co-use, and other factors.

A systematic review of evidence on the association between cocaine use and seizures.

BACKGROUND: Institutional monographs/medical textbooks mention seizures as a neurological complication of cocaine, but no systematic reviews (SRs) have been published on this issue. We aimed to conduct a SR of the literature on the relationship between cocaine use and seizures and to summarize the biological plausibility of that relationship. METHODS: The pathophysiological mechanisms that may underlie an association between cocaine and seizures were summarized; a SR was then performed using three databases (EMBASE, Medline, PsycINFO) and the Cochrane-library to search for published papers (1980-2012) aimed at quantifying the associations between cocaine use and seizures. The inclusion criteria for selection were: articles based on clinical trials, cohort, case-control (CC) or cross-sectional (CS) studies, participants ≥ 14 years old and not pregnant, and use of cocaine in the last 72 h. Information was extracted, evaluated and cross-checked independently by two researchers. RESULTS: Of the 1243 potentially relevant articles initially identified; one CC and 22 CS studies were finally selected. The CC study did not find cocaine use to be a risk-factor for seizures. In addition to the limitations of the CS design, these studies had important methodological weaknesses and biases. CONCLUSIONS: Despite its biological plausibility, no rigorous scientific evidence supports a causal relationship between cocaine use and seizures. The misinterpretation of the role of cocaine may have important implications in medical services. Well-conducted studies are urgently needed.

[Evolution of the need and coverage of syringe exchange programs in Spanish prisons, 1992-2009: A revised estimation]. / Evolución de la necesidad y cobertura de los programas de intercambio de jeringuillas en las prisiones españolas, 1992-2009: Una estimación corregida.

INTRODUCTION: The objective of this paper is to amend the bias included in our previous work, presenting a corrected estimation of the need and coverage of syringes/needles in Spanish prisons between 1992 and 2009. METHODS: Data on the provision of the needles exchange programs (NEPs) in prison is taken from official publications. The need was calculated by applying multiplicative methods to secondary data from several sources. Coverage was estimated as the quotient between provision and need and the difference between these magnitudes. The detected need estimate bias has been corrected. RESULTS: NEP's in prisons started in 1997. Their maximum coverage reached 36% in 2005, which is much higher than the initially estimated value. However, it decreased by half in the next four years, reaching 17.4% in 2009. CONCLUSION: The remarkable coverage reached by these programmes must be valued, but more recent evolution leads us to emphasize the need to be imaginative so that new epidemiological and economic circumstances do not lead to their disappearance.

[Evolution of the need and coverage of opioid substitution treatments and needle exchange programmes in Spanish prisons, 1992-2009]. / Evolución de la necesidad y cobertura de los programas de tratamiento con sustitutivos opioides e intercambio de jeringas en las prisiones españolas, 1992-2009.

INTRODUCTION: Spain is one of the few countries to have widely implemented opioid substitution treatments (OST) and needle exchange programmes (NEP) for drug users in prison. We analyze the evolution of the need, coverage and the timeliness of these interventions in Spain between 1992 and 2009. METHODS: Data on the provision of interventions is taken from official publications. The need was calculated by applying multiplicative methods to secondary data from several sources. Coverage was estimated as the quotient between provision and need. Temporal opportunity was estimated by observing the gap between the acme of the incidence of consumption, of HIV infection or need and the curve of provision. RESULTS: OST's began to be implemented in 1992. In 2002 they reached their maximum coverage (63.8%) and subsequently stabilized. NEP's started in 1997. Their maximum coverage reached 20.7% in 2006, but halved in a period of two years. The delay between the epidemic acme and the need and maximum intervention coverage was of 8-25 years. CONCLUSIONS: OST and NEP introduction in Spanish prisons was a great advance, but the delay in their implementation and the low level of NEP coverage could have limited their potential impact on the improvement of the health of incarcerated drug users. The decline of NEP coverage in recent years is a cause of major concern for the evolution of HIV and Hepatitis C epidemics.

Depression among regular heroin users: the influence of gender.

The aim of this study was to determine the prevalence of recent (last 12 months) depression in regular young heroin users and to ascertain factors associated with depression in this population, broken down by gender. A sample of 561 participants completed a cross-sectional survey. Eligibility criteria were: age 30 years or younger, and having used heroin for at least 12 days in the last 12 months and at least one day in the last 3 months. Participants were recruited outside of health-care facilities in the cities of Barcelona, Madrid and Seville by targeted sampling and chain referral methods. Depression was assessed using the World Mental Health Composite International Diagnostic Interview. The prevalence of recent depression was 22.3% (35.2% among women and 17.3% among men, p<0.001). In the multivariate analysis, the factors positively associated with recent depression in the whole sample were female gender, age 25 or less, inability to work due to health problems and high risk consumption of alcohol. Among woman, the related variables were age 25 or less, cocaine dependence in the last 12 months, and alcohol consumption in that period. Among men, employment status was the only related variable. Analysis of an overall sample without the gender breakdown may hide important differences in the factors associated with depression in men and women. Both prevention and treatment of depression should rely on specific gender analysis.

Allergy to low dose sugammadex.

We describe the case of a fit 17-year-old man who developed a severe allergic reaction to a low clinical dose of sugammadex (3.2 mg kg(-1) , 200 mg intravenously), 1 min after its administration. This was manifest by an intense erythema over the anterior part of the thorax, severe lip and palpebral oedema and bilateral wheeze. On later investigation, the patient had a positive skin prick test to sugammadex (5-mm diameter response, with a negative saline control and positive histamine control of 5 mm) and no response to any other drug tested. Other diagnostic tests supported a diagnosis of allergic reaction to sugammadex.

Donor-specific antibody detection: comparison of single antigen assay and Luminex crossmatches.

Luminex bead-based assays are routinely used in the study of anti-human leukocyte antigen (HLA) donor-specific antibodies (DSA). Single antigen (SA) assays use beads coated with recombinant antigens whereas Luminex crossmatch (Xm-DSA) tests consist of beads coated with isolated donor-specific HLA molecules. The aim of this study was to compare these techniques used to detect DSA. A total of 24 sera recognizing different HLA class I (seven anti-HLA-A and seven anti-HLA-B) as well as class II (seven anti-HLA-DR and three anti-HLA DQ) specificities by complement dependent cytotoxicity were included in the study. These sera were used undiluted and in serial dilutions to perform both class I and II SA and Xm-DSA assays. In the case of Xm-DSA the same serum was checked with different lysates. A total of 42 lysates were used to perform a total of 61 crossmatches: 42 to detect anti-class I and 19 to detect anti-class II antibodies. The maximum positive dilution was higher for SA in 76% of the class I and in 90% of the class II crossmatches. Those cases with a higher sensitivity of the Xm-DSA could not be explained by a larger number of antigen targets.

No association of TAP and LMP genetic polymorphism in human brucellosis and its complications.

Molecules involved in antigen processing (LMP) and peptide transport (TAP) are coded by polymorphic genes. This polymorphism may influence the peptide antigen selection process and play a role in the pathogenesis of human brucellosis. We studied the polymorphism of the antigen processing and transport genes (LMP and TAP) in 61 patients with human brucellosis and 102 controls from southern Spain. We found no differences in the frequencies of the LMP and TAP genotypes between the patients and the controls. Study of the patients with and without focal or complicated forms showed a significant increase in the TAP2A/TAP2F genotype in those with focal forms compared with those without focal forms (16% vs 0%, p = 0.02), though this difference lost its significance after correction for the number of comparisons. This study suggests that larger studies will be needed to confirm or rule out the possible association of the TAP2A/TAP2F genotype or other possible associations with focal forms of brucellosis.

Usefulness of a quantitative real-time PCR assay using serum samples to discriminate between inactive, serologically positive and active human brucellosis.

Diagnosis of brucellosis can be difficult in certain scenarios where conventional microbiological techniques have important limitations. The aim of this study was to develop a LightCycler Quantitative PCR assay in serum samples to discriminate between active and past brucellosis. In total, 110 serum samples from 46 brucellosis patients and 64 controls, including persons who had recently been treated for brucellosis, asymptomatic persons exposed to brucellosis, and patients with febrile syndromes involving a differential diagnosis with brucellosis, were studied. Brucella spp.-specific sequences of the PCR primers and probe were selected from the gene encoding an immunogenic membrane protein of 31 kDa (BCSP31). The analytical sensitivity was 1 x 10(1) fg of Brucella DNA. The mean threshold cycles for brucellosis patients and controls were 31.8 +/- 1.7 and 35.4 +/- 1.1, respectively (p <0.001). The best cut-off for bacterial DNA load was 5 x 10(3) copies/mL. At this cut-off, the area under the receiver operating characteristic curves was 0.963 (95% CI 0.920-1.005), with a sensitivity of 93.5% and a specificity of 98.4%. Under the assay conditions, the LightCycler Quantitative PCR in serum samples seems to be highly reproducible, rapid, sensitive and specific. It is therefore a useful method for both the initial diagnosis and the differentiation between past and active brucellosis.

[Exposure to environmental tobacco smoke at home increases the need for medical attention for respiratory diseases in childhood]. / La exposición al humo de tabaco en el hogar aumenta la frecuentación por patología respiratoria en la infancia.

OBJECTIVES: Children are highly vulnerable to damage from passive smoking as they are unable to avoid environmental tobacco, if present. Some reports have suggested that domestic exposure to environmental tobacco smoke can increase respiratory diseases in children. The aim of this study was to assess whether domestic passive smoking is associated with new respiratory events. METHODS: A descriptive, retrospective study was performed of 410 children aged less than 14 years old. The variables studied were: a) smokers in the household, b) the number of cigarettes smoked per day, c) school attendance, d) the number of siblings, e) previous respiratory diseases among parents and siblings, f) maternal smoking in pregnancy, and g) the number of respiratory events recorded in the previous year. Univariate, bivariate and multivariate analyses were performed. RESULTS: A total of 50.2 % of the children cohabited with smokers at home. The mean number of upper respiratory tract events per child living in environments free of tobacco smoke was 2.53 versus 3.52 when one of the household members smoked. For respiratory disease as a whole, an inverse association with age was found [OR = 0.83; (95 % CI: 0.76-0.90)] and a direct association was found with maternal smoking [OR = 4.56 (95 % CI; 1.84-11.34)]. With upper respiratory tract disease, the OR was 1.4 if the mother smoked 11-20 cigarettes/day, and was 1.9 if the number of cigarettes was > 20. With lower respiratory diseases, the odds ratio was 3.48 (95 % CI; 2.07-6.06) if the mother smoked. CONCLUSIONS: Fifty percent of the children studied were exposed to environmental tobacco smoke in the home. Younger children were at higher risk. The major risk factor for respiratory disease was maternal smoking and the risk increased with the number of cigarettes smoked. Health education is essential to protect children from tobacco smoke exposure.

Polymorphism of the transmembrane region of the MICA gene and human brucellosis.

We investigated the polymorphism of the transmembrane region of the MICA gene (major histocompatibility complex class I chain-related gene A) in relation to susceptibility to human brucellosis. We typed 114 patients with brucellosis and 121 healthy controls for MICA transmembrane polymorphism with polymerase chain reaction methods combined with fluorescent technology. We found a significant decrease in the frequency of the MICA-A4 allele in the patients with brucellosis compared with the controls (4.4% vs 10.3%, Pc = 0.03). The frequency of the MICA-A5 allele was increased in the group of patients with focal complications (15% vs 38%, Pc = 0.004). Our data suggest the MICA-A4 allele shows a tendency to be protective against infection by Brucella melitensis. Furthermore, the MICA-A5 allele appears to confer susceptibility to focal forms in patients with brucellosis.

Prevalence of HIV infection among young adult injecting and non-injecting heroin users in Spain in the era of harm reduction programmes: gender differences and other related factors.

The aims were to assess the prevalence of HIV infection among young adult heroin users, including injecting heroin users (IHUs) and non-injecting heroin users (NIHUs), and to explore the differences by gender and other factors. The design was a cross-sectional cohort study between April 2001 and December 2003, which included 961 current heroin users (HU), aged 18-30 years: 422 in Madrid, 351 in Barcelona and 188 in Seville; 621 were IHUs and 340 were NIHUs. All were street-recruited by chain referral methods. Face-to-face interviews were conducted using a structured questionnaire with computer-assisted personal interviewing (CAPI). Samples for HIV testing (dried blood spot) were collected and tested with ELISA and Western Blot. Bivariate, logistic regression, and classification and regression tree analyses were performed. The overall prevalence of HIV infection among IHUs was 25.8% (95% CI 22.3-29.3) [32.4% (95% CI 26.6-38.1) in Madrid, 20.5% (95% CI 15.6-25.4) in Barcelona, and 20.6% (95% CI 9.8-31.4) in Seville], whereas in NIHUs it was 4.0% (95% CI 2.1-6.7), with no differences among cities. The prevalence was significantly higher in women than in men in NIHUs (10.9%, 95% CI 4.3-17.5 vs. 1.7%, 95% CI 0.5-4.2) and was non-significantly higher in IHUs (30.4%, 95% CI 23.0-37.8 vs. 24.1%, 95% CI 20.1-28.1). HIV prevalence in short-term IHUs was 12.9% (CI 8.8-17.02), with no differences among cities. In the logistic analysis, the variables associated with infection in IHUs were ever having injected with used syringes (OR 3.4, 95% CI 2.2-5.3), ever having been in prison (OR 2.6, 95% CI 1.6-4.0), and heroin as the first drug injected at least weekly (OR 2.3, 95% CI 1.1-4.5). Factors positively associated with HIV infection in NIHUs were female sex (OR 8.7, 95% CI 2.6-29.2) and age >25 years (OR 3.1, 95% CI 0.9-11.1), while primary educational level was inversely associated (OR 0.26, 95% CI 0.1-0.9). Although there are important geographic differences, HIV prevalence in IHUs remains high, even in short-term IHUs, whereas it was almost six times lower in NIHUs. The prevalence in women is higher than in men, particularly among NIHUs. A wide range of preventive strategies should be developed, aimed primarily at empowering women to negotiate safe sex.

Tolerogenic response: allorecognition pathways.

The induction of immune tolerance in transplant recipients has been sought for many years but only a fundamental understanding of the immunological mechanisms underlying graft rejection will allow manipulation of the anti-graft immune response. In general, acute rejection is better understood and treated than chronic rejection, as they occur through partially different mechanisms. It is now generally accepted that recognition of same-species, non-self antigens (allorecognition) occurs through at least two different mechanisms, the direct and indirect pathways. In the direct pathway, donor MHC molecules on the surface of donor antigen-presenting cells (APCs) are recognised directly by the recipient's T cells. This mechanism is so immediate that it seems to be primarily involved in acute graft rejection. Since APCs of donor origin are depleted with time a second mechanism, the indirect pathway, takes over to cause chronic rejection, in which foreign MHC molecules are internalised, partially digested and presented as peptides to recipient T cells. Nonetheless, a number of studies are only fully understood when a third proposed allorecognition mechanism is taken into account. This is the semi-indirect pathway, as discussed in this short report.

[Functional ability and social-care problems of the elderly in the Cáceres health area]. / Capacidad funcional y problemas socioasistenciales de los ancianos del área de salud de Cáceres.

OBJECTIVE: To describe the social environment and to identify the health problems and the functional and mental ability of the elderly in the community. DESIGN: Cross-sectional, observational study by means of a questionnaire. PATIENTS: 228 people over 71 and not living in an institution. SETTING: Cáceres Health Area. MAIN MEASUREMENTS: Questionnaire on social and demographic details, main pathologies, social assessment (Gijón scale), functional assessment (Barthel and Lawton-Brody scales), mental assessment (Pfeiffer test), geriatric problems and visits from health professionals. RESULTS: 67% of the 228 people in the sample were women, with an average age of 79. Comorbidity, present in over 70% of the elderly, was significantly related to multi-medication, falls, hospital admission, depression and insomnia. The most common social and family situation was of a person living with his/her partner (38.3%; CI, 6.31) or children, in a dwelling with architectural barriers (43.0%; CI, 6.43), with a good relationship to his/her social surroundings (61.0%; CI, 6.33). The Barthel test showed a significant relationship with all the geriatric problems declared. The Pfeiffer test showed a relationship with falls (t=3.10; P=.00214), with hearing problems (t=1.98; P=.048), with incontinence (t=3.59; P=.0040) and constipation (t=2.64; P=.0086). The Lawton-Brody test was related, in women, with falls (t=4.27; P=.00034), admissions (t=2.02; P=.044), constipation and sight and hearing problems; and in men, with depression and incontinence. CONCLUSIONS: Elderly people in the Cáceres Health Area showed good functional ability in their basic daily tasks, less ability in instrumental activities and high comorbidity.

Metabolic flux analysis of pykF gene knockout Escherichia coli based on 13C-labeling experiments together with measurements of enzyme activities and intracellular metabolite concentrations.

Metabolic flux analysis based on 13C-labeling experiments followed by the measurement of intracellular isotope distribution using both 2D NMR and GC-MS was carried out to investigate the effect of pyruvate kinase (pyk) gene knockout on the metabolism of Escherichia coli in continuous culture. In addition, the activities of 16 enzymes, and the concentrations of 5 intracellular metabolites, were measured as a function of time in batch culture as well as continuous culture. It was found that flux through phosphoenol pyruvate carboxylase and malic enzyme were up-regulated in the pykF- mutant as compared with the wild type, and acetate formation was significantly reduced in the mutant. In addition, flux through the phosphofructose kinase pathway was reduced and that through the oxidative pentose phosphate (PP) pathway increased in the mutant. This was evidenced by the corresponding enzyme activities, and the increase in the concentrations of phosphoenol pyruvate, glucose-6-phosphate and 6-phosphogluconate, etc. It was also found for continuous cultivation that the enzyme activities of the oxidative PP and Entner-Doudoroff pathways increased as the dilution rate increased for the pykF- mutant. To clarify the metabolism quantitatively, it was found to be quite important to integrate the information on intracellular metabolic flux distribution, enzyme activities and intracellular metabolite concentrations.

Polymorphisms of the interferon gamma and interleukin 10 genes in human brucellosis.

We genotyped 83 patients with brucellosis and 101 controls to determine the influence of polymorphisms of the interferon gamma (IFNG) and interleukin 10 (IL10) genes on protection against, or susceptibility to, human brucellosis and its complications. The results showed a significant increase in the IFNG +874A/A genotype in patients compared with controls (34% vs. 19%) (P = 0.023, odds ratio = 2.17, 95% confidence interval 1.05-4.51). No significant differences were detected in the frequency distribution of the IL10 genotypes between patients and controls. Similarly, no significant differences were observed in the genotype frequencies of either of the two cytokines between complicated and non-complicated forms of brucellosis. Persons who are homozygous for the IFNG +874A allele may have a higher risk of contracting brucellosis.

Lessons from the history of the human immunodeficiency virus/acquired immunodeficiency syndrome epidemic among Spanish drug injectors.

In Spain, approximately 10 years passed between the time when human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) harm-reduction programs should have been developed with sufficient coverage to have an optimum impact on public health (before the HIV/AIDS epidemic's explosion in 1984) and the date of their actual implementation. This delay yielded an enormous cost for the country. The introduction of the virus in drug injector networks during a period of widespread diffusion of heroin injection and the lack of political awareness of the growing problem were 2 important factors that contributed to the important diffusion of the HIV infection among Spanish injection drug users. Lessons can be learned that may be of great interest in countries or territories facing similar challenges now and in the future.