Parasite load and risk factors for poor outcome among children with visceral leishmaniasis. A cohort study in Belo Horizonte, Brazil, 2010-2011

Clinical and laboratory risk factors for death from visceral leishmaniasis (VL) are relatively known, but quantitative real-time polymerase chain reaction (qPCR) might assess the role of parasite load in determining clinical outcome. The aim of this study was to identify risk factors, including parasite load in peripheral blood, for VL poor outcome among children. This prospective cohort study evaluated children aged ≤ 12 years old with VL diagnosis at three times: pre-treatment (T0), during treatment (T1) and post-treatment (T2). Forty-eight patients were included and 16 (33.3%) met the criteria for poor outcome. Age ≤ 12 months [relative risk (RR) 3.51; 95% confidence interval (CI) 1.89-6.52], tachydyspnoea (RR 3.46; 95% CI 2.19-5.47), bacterial infection (RR 3.08; 95% CI 1.27-7.48), liver enlargement (RR 3.00; 95% CI 1.44-6.23) and low serum albumin (RR 7.00; 95% CI 1.80-27.24) were identified as risk factors. qPCR was positive in all patients at T0 and the parasite DNA was undetectable in 76.1% of them at T1 and in 90.7% at T2. There was no statistical association between parasite load at T0 and poor outcome.

Obesity trends and body mass index changes after starting antiretroviral treatment : the Swiss HIV Cohort Study

BACKGROUND: The factors that contribute to increasing obesity rates in human immunodeficiency virus (HIV)-positive persons and to body mass index (BMI) increase that typically occurs after starting antiretroviral therapy (ART) are incompletely characterized. METHODS: We describe BMI trends in the entire Swiss HIV Cohort Study (SHCS) population and investigate the effects of demographics, HIV-related factors, and ART on BMI change in participants with data available before and 4 years after first starting ART. RESULTS: In the SHCS, overweight/obesity prevalence increased from 13% in 1990 (n = 1641) to 38% in 2012 (n = 8150). In the participants starting ART (n = 1601), mean BMI increase was 0.92 kg/m(2) per year (95% confidence interval, .83-1.0) during year 0-1 and 0.31 kg/m(2) per year (0.29-0.34) during years 1-4. In multivariable analyses, annualized BMI change during year 0-1 was associated with older age (0.15 [0.06-0.24] kg/m(2)) and CD4 nadir <199 cells/µL compared to nadir >350 (P < .001). Annualized BMI change during years 1-4 was associated with CD4 nadir <100 cells/µL compared to nadir >350 (P = .001) and black compared to white ethnicity (0.28 [0.16-0.37] kg/m(2)). Individual ART combinations differed little in their contribution to BMI change. CONCLUSIONS: Increasing obesity rates in the SHCS over time occurred at the same time as aging of the SHCS population, demographic changes, earlier ART start, and increasingly widespread ART coverage. Body mass index increase after ART start was typically biphasic, the BMI increase in year 0-1 being as large as the increase in years 1-4 combined. The effect of ART regimen on BMI change was limited.

Increased risks of early sexual initiators: time makes a difference.

BACKGROUND: Years since onset of sexual intercourse (YSSI) is a rarely used variable when studying adolescents- sexual outcomes. The aim of this study is to evaluate the influence of YSSI on the adverse sexual outcomes of early sexual initiators.METHODS: Data were drawn from the 2002 Swiss Multicenter Adolescent Survey on Health database, a nationally representative cross-sectional survey including 7429 adolescents in post mandatory school aged 16-20 years. Only adolescents reporting sexual intercourse (SI) were included (N=4388; 45% females) and divided by age of onset of SI (early initiators, age<16: N=1469, 44% females; and late initiators, age?16: N=2919, 46% females). Analyses were done separately by gender. Groups were compared for personal characteristics at the bivariate level. We analyzed three sexual outcomes (?4 sexual partners, pregnancy and non-use of condom at last SI) controlling for all significant personal variables with two logistic regressions first using age, then YSSI as one of the confounding variables. Results are given as adjusted odds ratios (aOR) using lSI as the reference category.RESULTS: After adjusting for YSSI instead of age, negative sexual outcomes among early initiators were no longer significant, except for multiple sexual partners among females, although at a much lower level. Early initiators were less likely to report non-use of condom at last SI when adjusting for YSSI (females: aOR=0.59 [0.44-0.79]; p<0.001; males aOR=0.71 [0.50-1.00]; p=0.053).CONCLUSION: YSSI is an important explanatory variable when studying adolescents- sexuality and needs to be included in future research on adolescents- sexual health.

Preparation of bacterial DNA template by boiling and effect of immunoglobulin G as an inhibitor in real-time PCR for serum samples from patients with brucellosis.

Real-time PCR is a widely used tool for the diagnosis of many infectious diseases. However, little information exists about the influences of the different factors involved in PCR on the amplification efficiency. The aim of this study was to analyze the effect of boiling as the DNA preparation method on the efficiency of the amplification process of real-time PCR for the diagnosis of human brucellosis with serum samples. Serum samples from 10 brucellosis patients were analyzed by a SYBR green I LightCycler-based real-time PCR and by using boiling to obtain the DNA. DNA prepared by boiling lysis of the bacteria isolated from serum did not prevent the presence of inhibitors, such as immunoglobulin G (IgG), which were extracted with the template DNA. To identify and confirm the presence of IgG, serum was precipitated to separate and concentrate the IgG and was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. The use of serum volumes above 0.6 ml completely inhibited the amplification process. The inhibitory effect of IgG in serum samples was not concentration dependent, and it could be eliminated by diluting the samples 1/10 and 1/20 in water. Despite the lack of the complete elimination of the IgG from the template DNA, boiling does not require any special equipment and it provides a rapid, reproducible, and cost-effective method for the preparation of DNA from serum samples for the diagnosis of brucellosis.

Detection of respiratory viruses by real-time polymerase chain reaction in outpatients with acute respiratory infection

Viruses are the major contributors to the morbidity and mortality of upper and lower acute respiratory infections (ARIs) for all age groups. The aim of this study was to determine the frequencies for a large range of respiratory viruses using a sensitive molecular detection technique in specimens from outpatients of all ages with ARIs. Nasopharyngeal aspirates were obtained from 162 individuals between August 2007-August 2009. Twenty-three pathogenic respiratory agents, 18 respiratory viruses and five bacteria were investigated using multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) and indirect immunofluorescence assay (IIF). Through IIF, 33 (20.4%) specimens with respiratory virus were recognised, with influenza virus representing over half of the positive samples. Through a multiplex real-time RT-PCR assay, 88 (54.3%) positive samples were detected; the most prevalent respiratory viral pathogens were influenza, human rhinovirus and respiratory syncytial virus (RSV). Six cases of viral co-detection were observed, mainly involving RSV. The use of multiplex real-time RT-PCR increased the viral detection by 33.9% and revealed a larger number of respiratory viruses implicated in ARI cases, including the most recently described respiratory viruses [human bocavirus, human metapneumovirus, influenza A (H1N1) pdm09 virus, human coronavirus (HCoV) NL63 and HCoV HKU1].

Rivaroxaban: Quantification by anti-FXa assay and influence on coagulation tests: a study in 9 Swiss laboratories.

INTRODUCTION: Rivaroxaban (RXA) is licensed for prophylaxis of venous thromboembolism after major orthopaedic surgery of the lower limbs. Currently, no test to quantify RXA in plasma has been validated in an inter-laboratory setting. Our study had three aims: to assess i) the feasibility of RXA quantification with a commercial anti-FXa assay, ii) its accuracy and precision in an inter-laboratory setting, and iii) the influence of 10mg of RXA on routine coagulation tests. METHODS: The same chromogenic anti-FXa assay (Hyphen BioMed) was used in all participating laboratories. RXA calibrators and sets of blinded probes (aim ii.) were prepared in vitro by spiking normal plasma. The precise RXA content was assessed by high-pressure liquid chromatography-tandem mass spectrometry. For ex-vivo studies (aim iii), plasma samples from 20 healthy volunteers taken before and 2 - 3hours after ingestion of 10mg of RXA were analyzed by participating laboratories. RESULTS: RXA can be assayed chromogenically. Among the participating laboratories, the mean accuracy and the mean coefficient of variation for precision of RXA quantification were 7.0% and 8.8%, respectively. Mean RXA concentration was 114±43μg/L .RXA significantly altered prothrombin time, activated partial thromboplastin time, factor analysis for intrinsic and extrinsic factors. Determinations of thrombin time, fibrinogen, FXIII and D-Dimer levels were not affected. CONCLUSIONS: RXA plasma levels can be quantified accurately and precisely by a chromogenic anti-FXa assay on different coagulometers in different laboratories. Ingestion of 10mg RXA results in significant alterations of both PT- and aPTT-based coagulation assays.

Estimation of the real population and its impact on the utilisation of healthcare services in Mediterranean resort regions: an ecological study.

BACKGROUND The demographic structure has a significant influence on the use of healthcare services, as does the size of the population denominators. Very few studies have been published on methods for estimating the real population such as tourist resorts. The lack of information about these problems means there is a corresponding lack of information about the behaviour of populational denominators (the floating population or tourist load) and the effect of this on the use of healthcare services. The objectives of the study were: a) To determine the Municipal Solid Waste (MSW) ratio, per person per day, among populations of known size; b) to estimate, by means of this ratio, the real population in an area where tourist numbers are very significant; and c) to determine the impact on the utilisation of hospital emergency healthcare services of the registered population, in comparison to the non-resident population, in two areas where tourist numbers are very significant. METHODS An ecological study design was employed. We analysed the Healthcare Districts of the Costa del Sol and the island of Menorca. Both are Spanish territories in the Mediterranean region. RESULTS In the two areas analysed, the correlation coefficient between the MSW ratio and admissions to hospital emergency departments exceeded 0.9, with p < 0.001. On the basis of MSW generation ratios, obtained for a control zone and also measured in neighbouring countries, we estimated the real population. For the summer months, when tourist activity is greatest and demand for emergency healthcare at hospitals is highest, this value was found to be double that of the registered population. CONCLUSION The MSW indicator, which is both ecological and indirect, can be used to estimate the real population in areas where population levels vary significantly during the year. This parameter is of interest in planning and dimensioning the provision of healthcare services.

Alteration in neuromuscular function after a 5 km running time trial

The aim of this study was to characterize the effect of a 5 km running time trial on the neuromuscular properties of the plantar flexors. Eleven well-trained triathletes performed a series of neuromuscular tests before and immediately after the run on a 200 m indoor track. Muscle activation (twitch interpolation) and normalized EMG activity were assessed during maximal voluntary contraction (MVC) of plantar flexors. Maximal soleus H-reflexes and M-waves were evoked at rest (i.e. H (MAX) and M (MAX), respectively) and during MVC (i.e. H (SUP) and M (SUP), respectively). MVC significantly declined (-27%; P < 0.001) after the run, due to decrease in muscle activation (-8%; P < 0.05) and M (MAX)-normalized EMG activity (-13%; P < 0.05). Significant reductions in M-wave amplitudes (M (MAX): -13% and M (SUP): -16%; P < 0.05) as well as H (MAX)/M (MAX) (-37%; P < 0.01) and H (SUP)/M (SUP) (-25%; P < 0.05) ratios occurred with fatigue. Following exercise, the single twitch was characterized by lower peak torque (-16%; P < 0.001) as well as shorter contraction (-19%; P < 0.001) and half-relaxation (-24%; P < 0.001) times. In conclusion, the reduction in plantar flexors strength induced by a 5 km running time trial is caused by peripheral adjustments, which are attributable to a failure of the neuromuscular transmission and excitation-contraction coupling. Fatigue also decreased the magnitude of efferent motor outflow from spinal motor neurons to the plantar flexors and part of this suboptimal neural drive is the result of an inhibition of soleus motoneuron pool reflex excitability.

Study and implementation of some quantitative trading models

Quantitative or algorithmic trading is the automatization of investments decisions obeying a fixed or dynamic sets of rules to determine trading orders. It has increasingly made its way up to 70% of the trading volume of one of the biggest financial markets such as the New York Stock Exchange (NYSE). However, there is not a signi cant amount of academic literature devoted to it due to the private nature of investment banks and hedge funds. This projects aims to review the literature and discuss the models available in a subject that publications are scarce and infrequently. We review the basic and fundamental mathematical concepts needed for modeling financial markets such as: stochastic processes, stochastic integration and basic models for prices and spreads dynamics necessary for building quantitative strategies. We also contrast these models with real market data with minutely sampling frequency from the Dow Jones Industrial Average (DJIA). Quantitative strategies try to exploit two types of behavior: trend following or mean reversion. The former is grouped in the so-called technical models and the later in the so-called pairs trading. Technical models have been discarded by financial theoreticians but we show that they can be properly cast into a well defined scientific predictor if the signal generated by them pass the test of being a Markov time. That is, we can tell if the signal has occurred or not by examining the information up to the current time; or more technically, if the event is F_t-measurable. On the other hand the concept of pairs trading or market neutral strategy is fairly simple. However it can be cast in a variety of mathematical models ranging from a method based on a simple euclidean distance, in a co-integration framework or involving stochastic differential equations such as the well-known Ornstein-Uhlenbeck mean reversal ODE and its variations. A model for forecasting any economic or financial magnitude could be properly defined with scientific rigor but it could also lack of any economical value and be considered useless from a practical point of view. This is why this project could not be complete without a backtesting of the mentioned strategies. Conducting a useful and realistic backtesting is by no means a trivial exercise since the \laws" that govern financial markets are constantly evolving in time. This is the reason because we make emphasis in the calibration process of the strategies' parameters to adapt the given market conditions. We find out that the parameters from technical models are more volatile than their counterpart form market neutral strategies and calibration must be done in a high-frequency sampling manner to constantly track the currently market situation. As a whole, the goal of this project is to provide an overview of a quantitative approach to investment reviewing basic strategies and illustrating them by means of a back-testing with real financial market data. The sources of the data used in this project are Bloomberg for intraday time series and Yahoo! for daily prices. All numeric computations and graphics used and shown in this project were implemented in MATLAB^R scratch from scratch as a part of this thesis. No other mathematical or statistical software was used.

Preinfarction angina prior to first myocardial infarction does not influence long-term prognosis: a retrospective study with subgroup analysis in elderly and diabetic patients.

BACKGROUND AND HYPOTHESIS Although prodromal angina occurring shortly before an acute myocardial infarction (MI) has protective effects against in-hospital complications, this effect has not been well documented after initial hospitalization, especially in older or diabetic patients. We examined whether angina 1 week before a first MI provides protection in these patients. METHODS A total of 290 consecutive patients, 143 elderly (>64 years of age) and 147 adults (<65 years of age), 68 of whom were diabetic (23.4%) and 222 nondiabetic (76.6%), were examined to assess the effect of preceding angina on long-term prognosis (56 months) after initial hospitalization for a first MI. RESULTS No significant differences were found in long-term complications after initial hospitalization in these adult and elderly patients according to whether or not they had prodromal angina (44.4% with angina vs 45.4% without in adults; 45.5% vs 58% in elderly, P < 0.2). Nor were differences found according to their diabetic status (61.5% with angina vs 72.7% without in diabetics; 37.3% vs 38.3% in nondiabetics; P = 0.4). CONCLUSION The occurrence of angina 1 week before a first MI does not confer long-term protection against cardiovascular complications after initial hospitalization in adult or elderly patients, whether or not they have diabetes.

Telehealth system (e-CUIDATE) to improve quality of life in breast cancer survivors: rationale and study protocol for a randomized clinical trial.

BACKGROUND Breast cancer survivors suffer physical impairment after oncology treatment. This impairment reduces quality of life (QoL) and increase the prevalence of handicaps associated to unhealthy lifestyle (for example, decreased aerobic capacity and strength, weight gain, and fatigue). Recent work has shown that exercise adapted to individual characteristics of patients is related to improved overall and disease-free survival. Nowadays, technological support using telerehabilitation systems is a promising strategy with great advantage of a quick and efficient contact with the health professional. It is not known the role of telerehabilitation through therapeutic exercise as a support tool to implement an active lifestyle which has been shown as an effective resource to improve fitness and reduce musculoskeletal disorders of these women. METHODS / DESIGN This study will use a two-arm, assessor blinded, parallel randomized controlled trial design. People will be eligible if: their diagnosis is of stages I, II, or IIIA breast cancer; they are without chronic disease or orthopedic issues that would interfere with ability to participate in a physical activity program; they had access to the Internet and basic knowledge of computer use or living with a relative who has this knowledge; they had completed adjuvant therapy except for hormone therapy and not have a history of cancer recurrence; and they have an interest in improving lifestyle. Participants will be randomized into e-CUIDATE or usual care groups. E-CUIDATE give participants access to a range of contents: planning exercise arranged in series with breathing exercises, mobility, strength, and stretching. All of these exercises will be assigned to women in the telerehabilitation group according to perceived needs. The control group will be asked to maintain their usual routine. Study endpoints will be assessed after 8 weeks (immediate effects) and after 6 months. The primary outcome will be QoL measured by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 version 3.0 and breast module called The European Organization for Research and Treatment of Cancer Breast Cancer-Specific Quality of Life questionnaire. The secondary outcomes: pain (algometry, Visual Analogue Scale, Brief Pain Inventory short form); body composition; physical measurement (abdominal test, handgrip strength, back muscle strength, and multiple sit-to-stand test); cardiorespiratory fitness (International Fitness Scale, 6-minute walk test, International Physical Activity Questionnaire-Short Form); fatigue (Piper Fatigue Scale and Borg Fatigue Scale); anxiety and depression (Hospital Anxiety and Depression Scale); cognitive function (Trail Making Test and Auditory Consonant Trigram); accelerometry; lymphedema; and anthropometric perimeters. DISCUSSION This study investigates the feasibility and effectiveness of a telerehabilitation system during adjuvant treatment of patients with breast cancer. If this treatment option is effective, telehealth systems could offer a choice of supportive care to cancer patients during the survivorship phase. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01801527.

Molecular diagnosis of strongyloidiasis in tropical areas: a comparison of conventional and real-time polymerase chain reaction with parasitological methods

This study aimed to evaluate the use of conventional polymerase chain reaction (cPCR) and real-time quantitative PCR (qPCR) in the diagnosis of human strongyloidiasis from stool samples in tropical areas. Stool samples were collected from individuals and were determined to be positive for Strongyloides stercoralis (group I), negative for S. stercoralis (group II) and positive for other enteroparasite species (group III). DNA specific to S. stercoralis was found in 76.7% of group I samples by cPCR and in 90% of group I samples by qPCR. The results show that molecular methods can be used as alternative tools for detecting S. stercoralis in human stool samples in tropical areas.

Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study

The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life.

Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study.

BACKGROUND Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.

ACTG-HIV symptoms changes in patients switched to RPV/FTC/TDF due to previous intolerance to CART. Interim analysis of the PRO-STR study.

INTRODUCTION Tolerability and convenience are crucial aspects for the long-term success of combined antiretroviral therapy (cART). The aim of this study was to investigate the impact in routine clinical practice of switching to the single tablet regimen (STR) RPV/FTC/TDF in patients with intolerance to previous cART, in terms of patients' well-being, assessed by several validated measures. METHODS Prospective, multicenter study. Adult HIV-infected patients with viral load under 1.000 copies/mL while receiving a stable ART for at least the last three months and switched to RPV/FTC/TDF due to intolerance of previous regimen, were included. Analyses were performed by ITT. Presence/magnitude of symptoms (ACTG-HIV Symptom Index), quality of life (EQ-5D, EUROQoL & MOS-HIV), adherence (SMAQ), preference of treatment and perceived ease of medication (ESTAR) through 48 weeks were performed. RESULTS Interim analysis of 125 patients with 16 weeks of follow up was performed. 100 (80%) were male, mean age 46 years. Mean CD4 at baseline was 629.5±307.29 and 123 (98.4%) had viral load <50 copies/mL; 15% were HCV co-infected. Ninety two (73.6%) patients switched from a NNRTI (84.8% from EFV/FTC/TDF) and 33 (26.4%) from a PI/r. The most frequent reasons for switching were psychiatric disorders (51.2%), CNS adverse events (40.8%), gastrointestinal (19.2%) and metabolic disorders (19.2%). At the time of this analysis (week 16), four patients (3.2%) discontinued treatment: one due to adverse events, two virologic failures and one with no data. A total of 104 patients (83.2%) were virologically suppressed (<50 copies/mL). The average degree of discomfort in the ACTG-HIV Symptom Index significantly decreased from baseline (21±15.55) to week 4 (10.89±12.36) & week 16 (10.81±12.62), p<0.001. In all the patients, quality of life tools showed a significant benefit in well-being of the patients (Table 1). Adherence to therapy significantly and progressively increased (SMAQ) from baseline (54.4%) to week 4 (68%), p<0.001 and to week 16 (72.0%), p<0.001. CONCLUSIONS Switching to RPV/FTC/TDF from another ARV regimen due to toxicity, significantly improved the quality of life of HIV-infected patients, both in mental and physical components, and improved adherence to therapy while maintaining a good immune and virological response.