The Influence of Gene Environment Interaction on the Risk of Cognitive Impairment: Reducing Sexual Risk Behaviors and Alcohol Use in HIV-infected Adults

Memory deficits and executive dysfunction are highly prevalent among HIV-infected adults. These conditions can affect their quality of life, antiretroviral adherence, and HIV risk behaviors. Several factors have been suggested including the role of genetics in relation to HIV disease progression. This dissertation aimed to determine whether genetic differences in HIV-infected individuals were correlated with impaired memory, cognitive flexibility and executive function and whether cognitive decline moderated alcohol use and sexual transmission risk behaviors among HIV-infected alcohol abusers participating in an NIH-funded clinical trial comparing the efficacy of the adapted Holistic Health Recovery Program (HHRP-A) intervention to a Health Promotion Control (HPC) condition in reducing risk behaviors. A total of 267 individuals were genotyped for polymorphisms in the dopamine and serotonin gene systems. Results yielded significant associations for TPH2, GALM, DRD2 and DRD4 genetic variants with impaired executive function, cognitive flexibility and memory. SNPs TPH2 rs4570625 and DRD2 rs6277 showed a risk association with executive function (odds ratio = 2.5, p = .02; 3.6, p = .001). GALM rs6741892 was associated with impaired memory (odds ratio = 1.9, p = .006). At the six-month follow-up, HHRP-A participants were less likely to report trading sex for food, drugs and money (20.0%) and unprotected insertive or receptive oral (11.6%) or vaginal and/or anal sex (3.2%) than HPC participants (49.4%, p

What Are Effective Program Characteristics of Self-Management Interventions in Patients With Heart Failure? : An Individual Patient Data Meta-analysis

Background To identify those characteristics of self-management interventions in patients with heart failure (HF) that are effective in influencing health-related quality of life, mortality, and hospitalizations. Methods and Results Randomized trials on self-management interventions conducted between January 1985 and June 2013 were identified and individual patient data were requested for meta-analysis. Generalized mixed effects models and Cox proportional hazard models including frailty terms were used to assess the relation between characteristics of interventions and health-related outcomes. Twenty randomized trials (5624 patients) were included. Longer intervention duration reduced mortality risk (hazard ratio 0.99, 95% confidence interval [CI] 0.97–0.999 per month increase in duration), risk of HF-related hospitalization (hazard ratio 0.98, 95% CI 0.96–0.99), and HF-related hospitalization at 6 months (risk ratio 0.96, 95% CI 0.92–0.995). Although results were not consistent across outcomes, interventions comprising standardized training of interventionists, peer contact, log keeping, or goal-setting skills appeared less effective than interventions without these characteristics. Conclusion No specific program characteristics were consistently associated with better effects of self-management interventions, but longer duration seemed to improve the effect of self-management interventions on several outcomes. Future research using factorial trial designs and process evaluations is needed to understand the working mechanism of specific program characteristics of self-management interventions in HF patients.

Factores de riesgo asociados al desarrollo de bacteriemia en pacientes adultos cirróticos hospitalizados

Introducción: La Bacteriemia en pacientes cirróticos es una causa importante de morbimortalidad, en gran parte favorecida por la especial vulnerabilidad de esta población ante procesos infecciosos. El objetivo fue determinar los factores asociados al desarrollo de bacteriemia primaria y secundaria en pacientes con Cirrosis, hospitalizados en la Fundación Cardioinfantil – Instituto de Cardiología entre 01 enero de 2010 y 31 enero de 2016. Materiales y Métodos: Estudio de casos y controles en pacientes mayores de 18 años con cirrosis hepática conocida o confirmada durante la hospitalización. Se realizó un análisis descriptivo, un análisis bivariado para determinar las diferencias entre los casos y los controles con respecto a las variables independientes un análisis de asociación mediante un modelo de regresión logística no condicional con variable dependiente bacteriemia. Los resultados se expresan en odds ratios con intervalos de confianza al 95%. Resultados: Las condiciones asociadas a bacteriemia como factores de riesgo fueron: Enfermedad renal crónica OR 9,1 (IC 95% 2,4-34), Escala Meld > 10 puntos OR 4,0 (IC 95% 2,-34), Infección previa OR 7,2 (IC 95% 2,1-24), presencia de catéter central OR 12,0 (IC 95% 1,8-80), presencia de sonda vesical OR 21,1 (IC 95% 1,6-276), estudio endoscópico OR 3,9 (IC 95% 1,1-14). Discusión: Factores relacionados con las condiciones clínicas del paciente evaluadas por las escalas Meld y Child-Pugh, el antecedente de infección previa y la presencia de dispositivos para monitorear el estado del paciente aumentan el riesgo de bacteriemia en pacientes hospitalizados con cirrosis.

Características y perfil microbiológico de pacientes con colecistitis moderada y severa en Mederi de 2014 a 2016

Introducción: Las guías de Tokyo de 2013 lograron un consenso respecto al manejo antibiótico de la infección biliar. Sus recomendaciones están sustentadas en estudios internacionales de la epidemiología bacteriana, pero también recalcan la importancia de conocer la microbiología local para ajustar las guías de manejo. Materiales y métodos: Se diseñó un estudio descriptivo tipo serie de casos de pacientes tratados por colecistitis aguda moderada y severa en Méderi Hospital Universitario Mayor (HUM), describiendo los aislamientos microbiológicos y perfiles de resistencia de los cultivos de bilis tomados durante la cirugía. Resultados: Se analizaron 131 pacientes con una edad promedio de 63 años, la mayoría sin comorbilidades médicas. Se encontró un 48% de positividad en los cultivos, predominantemente enterobacterias siendo la más frecuente Escherichia coli, seguida de especies de Klebsiella y de Enterococcus. Los perfiles de resistencia evidenciaron un 93% de multisensibilidad antibiótica y se aislaron 4 microorganismos multirresistentes. No se encontraron diferencias en comorbilidades, alteraciones paraclínicas, presencia de síndrome biliar obstrutivo, pancreatitis o instrumentación previa de la vía biliar entre los pacientes con cultivo positivo y negativo. Conclusiones: Los resultados concuerdan con los reportes internacionales en cuanto a la flora bacteriana aislada, pero los perfiles de resistencia evidenciados en esta serie son diferentes a los que sustentan las guías de manejo de Tokio revisadas en 2013. Este hallazgo obliga a ajustar las guías de manejo institucionales con base en la epidemiología local.

Propiedades psicométricas de los instrumentos para la medición de la actividad física en adultos con discapacidad física relacionada con lesión de médula espinal: una revisión sistemática

Objetivo: Evaluar las propiedades psicométricas de los instrumentos para la medición de la actividad física en adultos de 18-65 años con discapacidad física por lesión de médula espinal. Materiales y métodos: Revisión sistemática. Las bases de datos de Medline, Scopus, Web of Science y 19 revistas especializadas fueron consultadas durante once días entre abril de 2015 y febrero de 2016 para identificar estudios originales de validación, sin límite de tiempo y que estuvieran publicados en español, francés y/o inglés. La calidad metodológica de los instrumentos de medición se evaluó usando las diferentes cajas de propiedades de la lista COSMIN. Resultados: Se identificaron 9229 referencias, de las cuales sólo 12 cumplieron los criterios de inclusión, dando como resultado 13 instrumentos de medición. Se evaluaron seis propiedades psicométricas. La propiedad más común fue la confiabilidad, además se observó que la calidad metodológica de los estudios incluidos no representa los resultados de las propiedades psicométricas de los instrumentos de medición. La calidad metodológica de los instrumentos para la evaluación de la actividad física en población con lesión medular espinal es “baja” para propiedades como consistencia interna, error de medición, sensibilidad, validez de criterio (con excepción del WISCI II que tiene buena validez) y excelente para validez de contenido y fiabilidad. Conclusión: Se ha encontrado que instrumentos empleados hasta el presente en la medición de la actividad física en población con discapacidad física relacionada con lesión de médula espinal han sido creados para otros tipos de discapacidad y otros instrumentos deben ser validados en futuros estudios.

Clinical Phenotype and Genetic Epidemiology of Schizophrenia in a Finnish Isolate

This study is part of the joint project "The Genetic Epidemiology and Molecular Genetics of schizophrenia in Finland" between the Departments of Mental Health and Alcohol Research, and Molecular Medicine at the National Public Health Institute. In the study, we utilized three nationwide health care registers: 1) the Hospital Discharge Register, 2) the Free Medication Register, and 3) the Disability Pension Register, plus the National Population Register, in order to identify all patients with schizophrenia born from 1940 to 1976 (N=33,731) in Finland, and their first degree-relatives. 658 patients with at least one parent born in a homogeneous isolate in northeastern Finland were identified, as well as 4904 familial schizophrenia patients with at least two affected siblings from the whole country. The comparison group was derived from the Health 2000 Study. We collected case records and reassessed the register diagnosis. Were contacted the isolate patients and a random sample of patients from the whole country to make diagnostic clinical interviews and to assess the negative and positive symptoms and signs of schizophrenia. In addition to these patients, we interviewed siblings who were initially healthy according to the Hospital Discharge Register. Of those with a register diagnosis of schizophrenia, schizoaffective or schizophreniform disorder, 69% received a record-based consensus diagnosis and 63% an interview-based diagnosis of schizophrenia. Patients with schizophrenia having first-degree relatives with psychotic disorder had more severe affective flattening and alogia than those who were the only affected individuals in their family. The novel findings were: 1) The prevalence of schizophrenia in the isolate was relatively high based on register (1.5%), case record (0.9-1.3%), and interview (0.7-1.2%) data. 2) Isolate patients, regardless of their familial loading for schizophrenia, had less delusions and hallucinations than the whole country familial patients, which may be related to the genetic homogeneity in the isolate. This phenotype encourages the use of endophenotypes in genetic analyses instead of diagnoses alone. 3) The absence of register diagnosis does not confirm that siblings are healthy, because 7.7% of siblings had psychotic symptoms already before the register diagnoses were identified in 1991. For genetic research, the register diagnosis should therefore be reassessed using either a structured interview or a best- estimate case note consensus diagnosis. Structured clinical interview methods need be considered also in clinical practice.

Clinical and technical factors associated with skin intrinsic fluorescence in subjects with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications(EDIC) studies have established multiyear mean hemoglobin A1c (HbA1c) as predictive of microvascular complications in persons with type 1 diabetes. However, multiyear mean HbA1c is not always available in the clinical setting. Skin advanced glycation end products (AGEs) are thought to partially reflect effects of hyperglycemia over time, and measurement of skin AGEs might be a surrogate for multiyear mean HbA1c. As certain AGEs fluoresce and skin fluorescence has been demonstrated to correlate with the concentration of skin AGEs, noninvasive measurement by skin intrinsic fluorescence(SIF) facilitates the exploration of the association of mean HbA1c and other clinical/technical factors with SIF using the detailed phenotypic database available in DCCT/EDIC.

Modern-day clinical course of type 1 diabetes mellitus after 30 years' duration:the diabetes control and complications trial/epidemiology of diabetes interventions and complications and Pittsburgh epidemiology of diabetes complications experience (1983-2005)

Clinical treatment goals of type 1 diabetes mellitus (T1DM) have changed since the Diabetes Control and Complications Trial (DCCT) demonstrated reduced long-term complications with intensive diabetes therapy. There have been few longitudinal studies to describe the clinical course of T1DM in the age of intensive therapy. Our objective was to describe the current-day clinical course of T1DM.

Achalasia: A review of clinical diagnosis, epidemiology, treatment and outcomes

Achalasia is a neurodegenerative motility disorder of the oesophagus resulting in deranged oesophageal peristalsis and loss of lower oesophageal sphincter function. Historically, annual achalasia incidence rates were believed to be low, approximately 0.5-1.2 per 100000. More recent reports suggest that annual incidence rates have risen to 1.6 per 100000 in some populations. The aetiology of achalasia is still unclear but is likely to be multi-factorial. Suggested causes include environmental or viral exposures resulting in inflammation of the oesophageal myenteric plexus, which elicits an autoimmune response. Risk of achalasia may be elevated in a sub-group of genetically susceptible people. Improvement in the diagnosis of achalasia, through the introduction of high resolution manometry with pressure topography plotting, has resulted in the development of a novel classification system for achalasia. This classification system can evaluate patient prognosis and predict responsiveness to treatment. There is currently much debate over whether pneumatic dilatation is a superior method compared to the Heller's myotomy procedure in the treatment of achalasia. A recent comparative study found equal efficacy, suggesting that patient preference and local expertise should guide the choice. Although achalasia is a relatively rare condition, it carries a risk of complications, including aspiration pneumonia and oesophageal cancer. The risk of both squamous cell carcinoma and adenocarcinoma of the oesophagus is believed to be significantly increased in patients with achalasia, however the absolute excess risk is small. Therefore, it is currently unknown whether a surveillance programme in achalasia patients would be effective or cost-effective.

Molecular Epidemiology of Escherichia coli isolates from Environmental, Food and Clinical Sources

In the present study diversity of E. coli in the water samples of Cochin estuary were studied for a period of 3 years ranging from January 2010- December 2012. The stations were selected based on the closeness to satellite townships and waste input. Two of the stations (Chitoor and Thevara) were fixed upstream, two in the central part of the estuary namely Bolgatty and Off Marine Science Jetty, and one at the Barmouth. Diversity was assessed in terms of serotypes, phylogenetic groups and genotypes. Two groups of seafood samples such as fish and shellfish collected from the Cochin estuary were used for isolation of E. coli. One hundred clinical E. coli isolates were collected from one public health centre, one hospital and five medical labs in and around Cochin City, Kerala. From our results it was clear that pathogen cycling is occurring through food, water and clinical sources. Pathogen cycling through food is very common and fish and shellfish that harbour these strains might pose potential health risk to consumer. Estuarine environment is a melting pot for various kinds of wastes, both organic and inorganic. Mixing up of waste water from various sources such as domestic, industries, hospitals and sewage released into these water bodies resulting in the co-existence of E. coli from various sources thus offering a conducive environment for horizontal gene transfer. Opportunistic pathogens might acquire genes for drug resistance and virulence turning them to potential pathogens. Prevalence of ExPEC in the Cochin estuary, pose threat to people who use this water for fishing and recreation. Food chain also plays an important role in the transit of virulence genes from the environments to the human. Antibiotic resistant E. coli are widespread in estuarine water, seafood and clinical samples, for reasons well known such as indiscriminate use of antibiotics in animal production systems, aquaculture and human medicine. Since the waste water from these sources entering the estuary provides selection pressure to drug resistant mutants in the environment. It is high time that the authorities concerned should put systems in place for monitoring and enforcement to curb such activities. Microbial contamination can limit people’s enjoyment of coastal waters for contact recreation or shellfish-gathering. E. coli can make people sick if they are present in high levels in water used for contact recreation or shellfish gathering. When feeding, shellfish can filter large volumes of seawater, so any microorganisms present in the water become accumulated and concentrated in the shellfish flesh. If E. coli contaminated shellfish are consumed the impact to human health includes gastroenteritis, urinary tract infections (UTIs), and bacteraemia. In conclusion, the high prevalence of various pathogenic serotypes and phylogenetic groups, multidrug-resistance, and virulence factor genes detected among E. coli isolates from stations close to Cochin city is a matter of concern, since there is a large reservoir of antibiotic resistance genes and virulence traits within the community, and that the resistance genes and plasmid-encoded genes for virulence were easily transferable to other strains. Given the severity of the clinical manifestations of the disease in humans and the inability and/or the potential risks of antibiotic administration for treatment, it appears that the most direct and effective measure towards prevention of STEC and ExPEC infections in humans and ensuring public health may be considered as a priority.

Trauma and envenoming caused by stingrays and other fish in a fishing community in Pontal do Paranapanema, state of São Paulo, Brazil: epidemiology, clinical aspects, and therapeutic and preventive measures

INTRODUÇÃO: Os acidentes causados por peixes são comuns em comunidades de pescadores fluviais no Brasil, sendo acidentes ocupacionais na maioria das vezes. Estas populações não têm informações dos mecanismos de trauma e envenenamento. MÉTODOS: Através de um questionário aplicado aos pescadores, foram obtidos dados clínicos e epidemiológicos sobre acidentes em Rosana, Pontal do Paranapanema, Estado de São Paulo, Brasil. Estes dados foram analisados e convertidos em um programa de prevenção e tratamento de acidentes através de um folheto de fácil assimilação RESULTADOS: Trinta e nove pescadores responderam o questionário. Todos os pacientes apresentaram ferimentos causados por algum peixe. Dos peixes mencionados, mandijubas (Pimelodus maculatus) foram os mais associados aos ferimentos, mas outros também causaram traumas. em relação às arraias, seis pescadores tinham sido envenenados. Dor intensa e úlceras foram os principais sintomas. Aproximadamente metade dos acidentados usou apenas medidas de tratamentos populares. CONCLUSÕES: Os pescadores apresentaram acidentes múltiplos por mandis, que são peçonhentos e causam dor intensa, assim como traumas por outros peixes, como surubins, traíras, corvinas de água doce e piranhas. Cerca de 16% dos entrevistados apresentaram envenenamento por arraias. Nossos dados e experiência prévia permitiram a criação de um folheto de fácil assimilação pelas populações locais que pode ajudar os pescadores de forma efetiva, em uma área extremamente carente de serviços de saúde e prevenção de doenças. Esta iniciativa é aplicável a toda a bacia do Rio da Prata, área extensa e de fauna similar.

Epidemiology, clinical signs, histopathology and molecular characterization of canine leproid granuloma: a retrospective study of cases from Brazil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Piranha Attacks on Humans in Southeast Brazil: Epidemiology, Natural History, and Clinical Treatment, with Description of a Bite Outbreak

There are many tales describing ferocious schools of piranha attacking humans, but there are few scientific data supporting such behavior. The very few documented instances of humans attacked and eaten by piranha schools include 3 that occurred after death by other causes (eg, heart failure and drowning). These predaceous fishes, however, do occasionally injure bathers and swimmers in lakes and rivers. The characteristic profile of most injuries is a single bite per victim, generally related to the fish defending its brood. This paper describes an outbreak of piranha bites in a dammed river portion in southeast Brazil. The outbreak was caused by the speckled piranha, Serrasalmus spilopleura, a widespread species which benefits from the growing tendency of damming rivers all over Brazil. This article focuses on the epidemiological and clinical aspects of the injuries, as well as on piranha biology, to gain a better understanding of the natural history of bite outbreaks.

Chapter I: Definitions, epidemiology, clinical presentation and prognosis

The concept of chronic critical limb ischaemia (CLI) emerged late in the history of peripheral arterial occlusive disease (PAOD). The historical background and changing definitions of CLI over the last decades are important to know in order to understand why epidemiologic data are so difficult to compare between articles and over time. The prevalence of CLI is probably very high and largely underestimated, and significant differences exist between population studies and clinical series. The extremely high costs associated with management of these patients make CLI a real public health issue for the future. In the era of emerging vascular surgery in the 1950s, the initial classification of PAOD by Fontaine, with stages III and IV corresponding to CLI, was based only on clinical symptoms. Later, with increasing access to non-invasive haemodynamic measurements (ankle pressure, toe pressure), the need to prove a causal relationship between PAOD and clinical findings suggestive of CLI became a real concern, and the Rutherford classification published in 1986 included objective haemodynamic criteria. The first consensus document on CLI was published in 1991 and included clinical criteria associated with ankle and toe pressure and transcutaneous oxygen pressure (TcPO(2)) cut-off levels <50 mmHg, <30 mmHg and <10 mmHg respectively). This rigorous definition reflects an arterial insufficiency that is so severe as to cause microcirculatory changes and compromise tissue integrity, with a high rate of major amputation and mortality. The TASC I consensus document published in 2000 used less severe pressure cut-offs (≤ 50-70 mmHg, ≤ 30-50 mmHg and ≤ 30-50 mmHg respectively). The thresholds for toe pressure and especially TcPO(2) (which will be also included in TASC II consensus document) are however just below the lower limit of normality. It is therefore easy to infer that patients qualifying as CLI based on TASC criteria can suffer from far less severe disease than those qualifying as CLI in the initial 1991 consensus document. Furthermore, inclusion criteria of many recent interventional studies have even shifted further from the efforts of definition standardisation with objective criteria, by including patients as CLI based merely on Fontaine classification (stage III and IV) without haemodynamic criteria. The differences in the natural history of patients with CLI, including prognosis of the limb and the patient, are thus difficult to compare between studies in this context. Overall, CLI as defined by clinical and haemodynamic criteria remains a severe condition with poor prognosis, high medical costs and a major impact in terms of public health and patients' loss of functional capacity. The major progresses in best medical therapy of arterial disease and revascularisation procedures will certainly improve the outcome of CLI patients. In the future, an effort to apply a standardised definition with clinical and objective haemodynamic criteria will be needed to better demonstrate and compare the advances in management of these patients.