Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis

Background

Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS).

Objectives

To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS.

Methods

Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed.

Results

Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral.

Conclusions

Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases.     

The effectiveness of online cognitive behavioral treatment in routine clinical practice

Context

Randomized controlled trails have identified online cognitive behavioral therapy as an efficacious intervention in the management of common mental health disorders.

Objective

To assess the effectiveness of online CBT for different mental disorders in routine clinical practice.

Design

An uncontrolled before-after study, with measurements at baseline, posttest, 6-week follow-up, and 1-year follow-up.

Participants & Setting

1500 adult patients (female: 67%; mean age: 40 years) with a GP referral for psychotherapy were treated at a Dutch online mental health clinic for symptoms of depression (n = 413), panic disorder (n = 139), posttraumatic stress (n = 478), or burnout (n = 470).

Interventions

Manualized, web-based, therapist-assisted CBT, of which the efficacy was previously demonstrated in a series of controlled trials. Standardized duration of treatment varied from 5 weeks (online CBT for Posttraumatic stress) to 16 weeks (online CBT for Depression).

Main Outcome Measures

Validated self-report questionnaires of specific and general psychopathology, including the Beck Depression Inventory, the Impact of Event Scale, the Panic Disorder Severity Scale-Self Report, the Oldenburg Burnout Inventory, and the Depression Anxiety Stress Scales.

Results

Treatment adherence was 71% (n = 1071). Study attrition was 21% at posttest, 33% at 6-week FU and 65% at 1-year FU. Mixed-model repeated measures regression identified large short-term reductions in all measures of primary symptoms (d = 1.9±0.2 to d = 1.2±0.2; P<.001), which sustained up to one year after treatment. At posttest, rates of reliable improvement and recovery were 71% and 52% in the completer sample (full sample: 55%/40%). Patient satisfaction was high.

Conclusions

Results suggest that online therapist-assisted CBT may be as effective in routine practice as it is in clinical trials. Although pre-treatment withdrawal and long-term outcomes require further study, results warrant continued implementation of online CBT.     

Knowledge of HIV Serodiscordance,Transmission, and Prevention among Couples in Durban,South Africa

Objective

Couples’ voluntary HIV counseling and testing (CVCT) significantly decreases HIV transmission within couples, the largest risk group in sub-Saharan Africa, but it is not currently offered in most HIV testing facilities. To roll out such an intervention, understanding locale-specific knowledge barriers is critical. In this study, we measured knowledge of HIV serodiscordance, transmission, and prevention before and after receipt of CVCT services in Durban.

Design

Pre- and post-CVCT knowledge surveys were administered to a selection of individuals seeking CVCT services.

Methods

Changes in knowledge scores were assessed with McNemar Chi-square tests for balanced data and generalized estimating equation methods for unbalanced data.

Results

The survey included 317 heterosexual black couples (634 individuals) who were primarily Zulu (87%), unemployed (47%), and had at least a secondary level education (78%). 28% of couples proved to be discordant. Only 30% of individuals thought serodiscordance between couples was possible pre‐CVCT compared to 95% post-CVCT. One-third thought there was at least one benefit of CVCT pre‐CVCT, increasing to 96% post‐CVCT. Overall, there were positive changes in knowledge about HIV transmission and prevention. However, many respondents thought all HIV positive mothers give birth to babies with AIDS (64% pre-CVCT, 59% post-CVCT) and that male circumcision does not protect negative men against HIV (70% pre-CVCT, 67% post-CVCT).

Conclusions

CVCT was well received and was followed by improvements in understanding of discordance, the benefits of joint testing, and HIV transmission. Country-level health messaging would benefit from targeting gaps in knowledge about serodiscordance, vertical transmission, and male circumcision.     

Analysis of clonal type-specific antibody reactions in Toxoplasma gondii seropositive humans from Germany by peptide-microarray

Background

Different clonal types of Toxoplasma gondii are thought to be associated with distinct clinical manifestations of infections. Serotyping is a novel technique which may allow to determine the clonal type of T. gondii humans are infected with and to extend typing studies to larger populations which include infected but non-diseased individuals.

Methodology

A peptide-microarray test for T. gondii serotyping was established with 54 previously published synthetic peptides, which mimic clonal type-specific epitopes. The test was applied to human sera (n = 174) collected from individuals with an acute T. gondii infection (n = 21), a latent T. gondii infection (n = 53) and from T. gondii-seropositive forest workers (n = 100).

Findings

The majority (n = 124; 71%) of all T. gondii seropositive human sera showed reactions against synthetic peptides with sequences specific for clonal type II (type II peptides). Type I and type III peptides were recognized by 42% (n = 73) or 16% (n = 28) of the human sera, respectively, while type II–III, type I–III or type I–II peptides were recognized by 49% (n = 85), 36% (n = 62) or 14% (n = 25) of the sera, respectively. Highest reaction intensities were observed with synthetic peptides mimicking type II-specific epitopes. A proportion of the sera (n = 22; 13%) showed no reaction with type-specific peptides. Individuals with acute toxoplasmosis reacted with a statistically significantly higher number of peptides as compared to individuals with latent T. gondii infection or seropositive forest workers.

Conclusions

Type II-specific reactions were overrepresented and higher in intensity in the study population, which was in accord with genotyping studies on T. gondii oocysts previously conducted in the same area. There were also individuals with type I- or type III-specific reactions. Well-characterized reference sera and further specific peptide markers are needed to establish and to perform future serotyping approaches with higher resolution.     

Circumcision of male children for reduction of future risk for HIV: acceptability among HIV serodiscordant couples in Kampala, Uganda

Introduction

The ultimate success of medical male circumcision for HIV prevention may depend on targeting male infants and children as well as adults, in order to maximally reduce new HIV infections into the future.

Methods

We conducted a cross-sectional study among heterosexual HIV serodiscordant couples (a population at high risk for HIV transmission) attending a research clinic in Kampala, Uganda on perceptions and attitudes about medical circumcision for male children for HIV prevention. Correlates of willingness to circumcise male children were assessed using generalized estimating equations methods.

Results

318 HIV serodiscordant couples were interviewed, 51.3% in which the female partner was HIV uninfected. Most couples were married and cohabiting, and almost 50% had at least one uncircumcised male child of ≤18 years of age. Overall, 90.2% of male partners and 94.6% of female partners expressed interest in medical circumcision for their male children for reduction of future risk for HIV infection, including 79.9% of men and 87.6% of women who had an uncircumcised male child. Among both men and women, those who were knowledgeable that circumcision reduces men''s risk for HIV (adjusted prevalence ratio [APR] 1.34 and 1.14) and those who had discussed the HIV prevention effects of medical circumcision with their partner (APR 1.08 and 1.07) were significantly (p≤0.05) more likely to be interested in male child circumcision for HIV prevention. Among men, those who were circumcised (APR 1.09, p = 0.004) and those who were HIV seropositive (APR 1.09, p = 0.03) were also more likely to be interested in child circumcision for HIV prevention.

Conclusions

A high proportion of men and women in Ugandan heterosexual HIV serodiscordant partnerships were willing to have their male children circumcised for eventual HIV prevention benefits. Engaging both parents may increase interest in medical male circumcision for HIV prevention.     

Thoracic empyema: a 12-year study from a UK tertiary cardiothoracic referral centre

Background

Empyema is an increasingly frequent clinical problem worldwide, and has substantial morbidity and mortality. Our objectives were to identify the clinical, surgical and microbiological features, and management outcomes, of empyema.

Methods

A retrospective observational study over 12 years (1999–2010) was carried out at The Heart Hospital, London, United Kingdom. Patients with empyema were identified by screening the hospital electronic ‘Clinical Data Repository’. Demographics, clinical and microbiological characteristics, underlying risk factors, peri-operative blood tests, treatment and outcomes were identified. Univariable and multivariable statistical analyses were performed.

Results

Patients (n = 406) were predominantly male (74.1%); median age = 53 years (IQR = 37–69). Most empyema were community-acquired (87.4%) and right-sided (57.4%). Microbiological diagnosis was obtained in 229 (56.4%) patients, and included streptococci (16.3%), staphylococci (15.5%), Gram-negative organisms (8.9%), anaerobes (5.7%), pseudomonads (4.4%) and mycobacteria (9.1%); 8.4% were polymicrobial. Most (68%) cases were managed by open thoracotomy and decortication. Video-assisted thoracoscopic surgery (VATS) reduced hospitalisation from 10 to seven days (P = 0.0005). All-cause complication rate was 25.1%, and 28 day mortality 5.7%. Predictors of early mortality included: older age (P = 0.006), major co-morbidity (P = 0.01), malnutrition (P = 0.001), elevated red cell distribution width (RDW, P<0.001) and serum alkaline phosphatase (P = 0.004), and reduced serum albumin (P = 0.01) and haemoglobin (P = 0.04).

Conclusions

Empyema remains an important cause of morbidity and hospital admissions. Microbiological diagnosis was only achieved in just over 50% of cases, and tuberculosis is a notable causative organism. Treatment of empyema with VATS may reduce duration of hospital stay. Raised RDW appears to associate with early mortality.     

Effects of preoperative aspirin on cardiocerebral and renal complications in non-emergent cardiac surgery patients: a sub-group and cohort study

Background and Objective

Postoperative cardiocerebral and renal complications are a major threat for patients undergoing cardiac surgery. This study was aimed to examine the effect of preoperative aspirin use on patients undergoing cardiac surgery.

Methods

An observational cohort study was performed on consecutive patients (n = 1879) receiving cardiac surgery at this institution. The patients excluded from the study were those with preoperative anticoagulants, unknown aspirin use, or underwent emergent cardiac surgery. Outcome events included were 30-day mortality, renal failure, readmission and a composite outcome - major adverse cardiocerebral events (MACE) that include permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block and cardiac arrest.

Results

Of all patients, 1145 patients met the inclusion criteria and were divided into two groups: those taking (n = 858) or not taking (n = 287) aspirin within 5 days preceding surgery. Patients with aspirin presented significantly more with history of hypertension, diabetes, peripheral arterial disease, previous MI, angina and older age. With propensity scores adjusted and multivariate logistic regression, however, this study showed that preoperative aspirin therapy (vs. no aspirin) significantly reduced the risk of MACE (8.4% vs. 12.5%, odds ratio [OR] 0.585, 95% CI 0.355–0.964, P = 0.035), postoperative renal failure (2.6% vs. 5.2%, OR 0.438, CI 0.203–0.945, P = 0.035) and dialysis required (0.8% vs. 3.1%, OR 0.230, CI 0.071–0.742, P = 0.014), but did not significantly reduce 30-day mortality (4.1% vs. 5.8%, OR 0.744, CI 0.376–1.472, P = 0.396) nor it increased readmissions in the patients undergoing cardiac surgery.

Conclusions

Preoperative aspirin therapy is associated with a significant decrease in the risk of MACE and renal failure and did not increase readmissions in patients undergoing non-emergent cardiac surgery.     

Incidence and risk factors of serious adverse events during antituberculous treatment in Rwanda: a prospective cohort study

Background

Tuberculosis (TB) and TB-human immunodeficiency virus infection (HIV) coinfection is a major public health concern in resource-limited settings. Although TB treatment is challenging in HIV-infected patients because of treatment interactions, immunopathological reactions, and concurrent infections, few prospective studies have addressed this in sub-Saharan Africa.In this study we aimed to determine incidence, causes of, and risk factors for serious adverse events among patients on first-line antituberculous treatment, as well as its impact on antituberculous treatment outcome.

Methods and findings

Prospective observational cohort study of adults treated for TB at the Internal Medicine department of the Kigali University Hospital from May 2008 through August 2009.Of 263 patients enrolled, 253 were retained for analysis: median age 35 (Interquartile range, IQR 28–40), 55% male, 66% HIV-positive with a median CD4 count 104 cells/mm³ (IQR 44–248 cells/mm³). Forty percent had pulmonary TB, 43% extrapulmonary TB and 17% a mixed form. Sixty-four (26%) developed a serious adverse event; 58/167 (35%) HIV-infected vs. 6/86 (7%) HIV-uninfected individuals. Commonest events were concurrent infection (n = 32), drug-induced hepatitis (n = 24) and paradoxical reactions/TB-IRIS (n = 23).HIV-infection (adjusted Hazard Ratio, aHR 3.4, 95% Confidence Interval, CI 1.4–8.7) and extrapulmonary TB (aHR 2, 95%CI 1.1–3.7) were associated with an increased risk of serious adverse events. For TB/HIV co-infected patients, extrapulmonary TB (aHR 2.0, 95%CI 1.1–3.9) and CD4 count <100 cells/mm3 at TB diagnosis (aHR 1.7, 95%CI 1.0–2.9) were independent predictors. Adverse events were associated with an almost two-fold higher risk of unsuccessful treatment outcome at 6 months (HR 1.89, 95%CI 1.3–3.0).

Conclusion

Adverse events frequently complicate the course of antituberculous treatment and worsen treatment outcome, particularly in patients with extrapulmonary TB and advanced immunodeficiency. Concurrent infection accounts for most events. Our data suggest that deterioration in a patient already receiving antituberculous treatment should prompt an aggressive search for additional infections.     

Consent for use of clinical leftover biosample: a survey among Chinese patients and the general public

Background

Storage of leftover biosamples generates rich biobanks for future studies, saving time and money and limiting physical impact to sample donors.

Objective

To investigate the attitudes of Chinese patients and the general public on providing consent for storage and use of leftover biosamples.

Design, Setting and Participants

Cross-sectional surveys were conducted among randomly selected patients admitted to a Shanghai city hospital (n = 648) and members of the general public (n = 492) from May 2010 to July 2010.

Main Outcome Measures

Face-to-face interviews collected respondents-report of their willingness to donate residual biosample, trust in medical institutions, motivation for donation, concerns of donated sample use, expectations for research results return, and so on.

Results

The response rate was 83.0%. Of the respondents, 89.1% stated that they completely understood or understood most of questions. Willingness to donate residual sample was stated by 64.7%, of which 16.7% desired the option to withdraw their donations anytime afterwards. Only 42.3% of respondents stated they “trust" or “strongly trust" medical institutions, the attitude of trusting or strongly trusting medical institutions were significantly associated with willingness to donate in the general public group.(p<0.05) The overall assent rate for future research without specific consents was also low (12.1%). Hepatitis B virus carriers were significantly less willing than non-carriers to donate biosamples (32.1% vs. 64.7%, p<0.001).

Conclusions

Low levels of public trust in medical institutions become serious obstacle for biosample donation and biobanking in China. Efforts to increase public understanding of human medical research and biosample usage and trust in the ethical purposes of biobanking are urgently needed. These efforts will be greatly advanced by the impending legislation on biobanking procedures and intent, and our results may help guide the structure of such law.     

Interferon-gamma release assay (modified QuantiFERON) as a potential marker of infection for Leishmania donovani, a proof of concept study

Background

In areas endemic for visceral leishmaniasis (VL), a large number of infected individuals mount a protective cellular immune response and remain asymptomatic carriers. We propose an interferon-gamma release assay (IFN-γRA) as a novel marker for latent L. donovani infection.

Methods and Findings

We modified a commercial kit (QuantiFERON) evaluating five different leishmania-specific antigens; H2B, H2B-PSA2, H2B-Lepp12, crude soluble antigen (CSA) and soluble leishmania antigen (SLA) from L. donovani with the aim to detect the cell-mediated immune response in VL. We evaluated the assay on venous blood samples of active VL patients (n = 13), cured VL patients (n = 15), non-endemic healthy controls (n = 11) and healthy endemic controls (n = 19). The assay based on SLA had a sensitivity of 80% (95% CI = 54.81–92.95) and specificity of 100% (95% CI = 74.12–100).

Conclusion

Our findings suggest that a whole-blood SLA-based QuantiFERON assay can be used to measure the cell-mediated immune response in L. donovani infection. The positive IFN-γ response to stimulation with leishmania antigen in patients with active VL was contradictory to the conventional finding of a non-proliferative antigen-specific response of peripheral blood mononuclear cells and needs further research.     

Gender inequity norms are associated with increased male-perpetrated rape and sexual risks for HIV infection in Botswana and Swaziland

Background

There is limited empirical research on the underlying gender inequity norms shaping gender-based violence, power, and HIV risks in sub-Saharan Africa, or how risk pathways may differ for men and women. This study is among the first to directly evaluate the adherence to gender inequity norms and epidemiological relationships with violence and sexual risks for HIV infection.

Methods

Data were derived from population-based cross-sectional samples recruited through two-stage probability sampling from the 5 highest HIV prevalence districts in Botswana and all districts in Swaziland (2004–5). Based on evidence of established risk factors for HIV infection, we aimed 1) to estimate the mean adherence to gender inequity norms for both men and women; and 2) to model the independent effects of higher adherence to gender inequity norms on a) male sexual dominance (male-controlled sexual decision making and rape (forced sex)); b) sexual risk practices (multiple/concurrent sex partners, transactional sex, unprotected sex with non-primary partner, intergenerational sex).

Findings

A total of 2049 individuals were included, n = 1255 from Botswana and n = 796 from Swaziland. In separate multivariate logistic regression analyses, higher gender inequity norms scores remained independently associated with increased male-controlled sexual decision making power (AORmen = 1.90, 95%CI:1.09–2.35; AORwomen = 2.05, 95%CI:1.32–2.49), perpetration of rape (AORmen = 2.19 95%CI:1.22–3.51), unprotected sex with a non-primary partner (AORmen = 1.90, 95%CI:1.14–2.31), intergenerational sex (AORwomen = 1.36, 95%CI:1.08–1.79), and multiple/concurrent sex partners (AORmen = 1.42, 95%CI:1.10–1.93).

Interpretation

These findings support the critical evidence-based need for gender-transformative HIV prevention efforts including legislation of women''s rights in two of the most HIV affected countries in the world.     

Virtual versus physical channel for sex networking in men having sex with men of sauna customers in the City of Hong Kong

Background

Advances in communication technology may affect networking pattern, thereby influencing the dynamics of sex partnership. The aim of the study is to explore the impacts of partner sourcing through internet and related channels on exposure risk to sexually transmitted infections (STI) including HIV.

Methods

Using venue-based sampling, a cross-sectional questionnaire survey was conducted at saunas frequented by men having sex with men (MSM) in Hong Kong. Comparison was made between MSM sourcing partners through physical venues alone versus concomitant users of physical and virtual channels, the latter referring to internet and smart-phone applications, using bivariate logistic regression.

Results

Over a 7-week study period, 299 MSM were recruited from 9 saunas. Three main types of sex partners were distinguished: steady (46.8%), regular (26.4%) and casual (96.0%) partners. Users of sauna (n = 78) were compared with concomitant users of saunas and virtual channels (n = 179) for partner sourcing. Sauna-visiting virtual channel users were younger and inclined to use selected physical venues for sourcing partners. Smart-phone users (n = 90) were not different from other internet-users in terms of age, education level and single/mixed self-identified body appearance. Classifying respondents into high risk and low risk MSM by their frequency of condom use, concomitant use of both sauna and virtual channels accounted for a higher proportion in the high risk category (71.6% vs. 58.2%, OR = 1.81, p<0.05). In virtual channel users, partner sourcing through smart-phone was not associated with a higher practice of unprotected sex.

Conclusion

MSM sauna customers commonly use virtual channels for sex partner sourcing. Unprotected sex is more prevalent in sauna customers who use virtual channel for sex partner sourcing. While the popularity of smart-phone is rising, its use is not associated with increased behavioural risk for HIV/STI transmission.     

A preliminary evaluation of limb salvage surgery for osteosarcoma around knee joint

Objective

To evaluate the effectiveness and drawbacks of diversified procedures of limb salvage surgery (LSS), providing a reference of rational surgical criterion of LSS.

Methods

Fifty eight patients with stage IIB extremity osteosarcoma around knee joint area between 1992 and 2002 were studied retrospectively. Among them, 43 patients were treated by LSS followed by reconstruction. Reconstruction approaches included re-implantation of irradiation-devitalized tumor bone (n = 12), autoclaving-devitalized tumor bone (n = 8), prosthetic replacement (n = 11), allograft transplantation (n = 8) and vascularized fibula autograft implantation (n = 4). Amputations were performed in 15 patients. Patients were followed up for 6–16 years.

Results

There were no significant difference between LSS and amputation groups regarding disease free survival and local recurrence rates. The actuarial 5-year continuous disease free survival and local recurrence rate were 30.0% and 25.0% in patients of devitalized LSS group, whereas those were 56.5% and 8.7% in patients of non-devitalized reconstruction group. The complication rate was significantly higher in LSS group compared to amputation group (P = 0.003).

Conclusion

LSS with non-devitalized procedures is the optimal treatment for osteosarcoma around knee joint area. Prosthesis implantation is the preferred option for bone reconstruction following LSS. Prevention and treatment of post-operative complications should be paid more attention to get good long-term outcomes of surgery.     

High prevalence of hypertension and placental insufficiency, but no in utero HIV transmission, among women on HAART with stillbirths in Botswana

Background

Increased stillbirth rates occur among HIV-infected women, but no studies have evaluated the pathological basis for this increase, or whether highly active antiretroviral therapy (HAART) influences the etiology of stillbirths. It is also unknown whether HIV infection of the fetus is associated with stillbirth.

Methods

HIV-infected women and a comparator group of HIV-uninfected women who delivered stillbirths were enrolled at the largest referral hospital in Botswana between January and November 2010. Obstetrical records, including antiretroviral use in pregnancy, were extracted at enrollment. Verbal autopsies; maternal HIV, CD4 and HIV RNA testing; stillbirth HIV PCR testing; and placental pathology (blinded to HIV and treatment status) were performed.

Results

Ninety-nine stillbirths were evaluated, including 62 from HIV-infected women (34% on HAART from conception, 8% on HAART started in pregnancy, 23% on zidovudine started in pregnancy, and 35% on no antiretrovirals) and 37 from a comparator group of HIV-uninfected women. Only 2 (3.7%) of 53 tested stillbirths from HIV-infected women were HIV PCR positive, and both were born to women not receiving HAART. Placental insufficiency associated with hypertension accounted for most stillbirths. Placental findings consistent with chronic hypertension were common among HIV-infected women who received HAART and among HIV-uninfected women (65% vs. 54%, p = 0.37), but less common among HIV-infected women not receiving HAART (28%, p = 0.003 vs. women on HAART).

Conclusions

In utero HIV infection was rarely associated with stillbirths, and did not occur among women receiving HAART. Hypertension and placental insufficiency were associated with most stillbirths in this tertiary care setting.     

Characterization of a large group of individuals with huntington disease and their relatives enrolled in the COHORT study

Background

Careful characterization of the phenotype and genotype of Huntington disease (HD) can foster better understanding of the condition.

Methods

We conducted a cohort study in the United States, Canada, and Australia of members of families affected by HD. We collected demographic and clinical data, conducted the Unified Huntington''s Disease Rating Scale and Mini-Mental State Examination, and determined Huntingtin trinucleotide CAG repeat length. We report primarily on cross-sectional baseline data from this recently completed prospective, longitudinal, observational study.

Results

As of December 31, 2009, 2,318 individuals enrolled; of these, 1,985 (85.6%) were classified into six analysis groups. Three groups had expanded CAG alleles (36 repeats or more): individuals with clinically diagnosed HD [n = 930], and clinically unaffected first-degree relatives who had previously pursued [n = 248] or not pursued [n = 112] predictive DNA testing. Three groups lacked expanded alleles: first-degree relatives who had previously pursued [n = 41] or not pursued [n = 224] genetic testing, and spouses and caregivers [n = 430]. Baseline mean performance differed across groups in all motor, behavioral, cognitive, and functional measures (p<0.001). Clinically unaffected individuals with expanded alleles weighed less (76.0 vs. 79.6 kg; p = 0.01) and had lower cognitive scores (28.5 vs. 29.1 on the Mini Mental State Examination; p = 0.008) than individuals without expanded alleles. The frequency of “high normal” repeat lengths (27 to 35) was 2.5% and repeat lengths associated with reduced penetrance (36 to 39) was 2.7%.

Conclusion

Baseline analysis of COHORT study participants revealed differences that emerge prior to clinical diagnosis. Longitudinal investigation of this cohort will further characterize the natural history of HD and genetic and biological modifiers.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00313495","term_id":"NCT00313495"}}NCT00313495     

Antiretroviral therapy outcomes in HIV-infected children after adjusting protease inhibitor dosing during tuberculosis treatment

Background

Modification of ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy is required for HIV-infected children co-treated for tuberculosis (TB). We aimed to determine virologic and toxicity outcomes among TB/HIV co-treated children with the following modifications to their antiretroviral therapy (ART): (1) super-boosted LPV/r, (2) double-dose LPV/r or (3) ritonavir.

Methods and Findings

A medical record review was conducted at two clinical sites in Johannesburg, South Africa. The records of children 6–24 months of age initiating LPV/r-based therapy were reviewed. Children co-treated for TB were categorized based on the modifications made to their ART regimen and were compared to children of the same age at each site not treated for TB.Included are 526 children, 294 (56%) co-treated for TB. All co-treated children had more severe HIV disease, including lower CD4 percents and worse growth indicators, than comparisons.Children in the super-boosted group (n = 156) were as likely to be virally suppressed (<400 copies/ml) at 6 months as comparisons (69.2% vs. 74.8%, p = 0.36). Children in the double-dose (n = 47) and ritonavir groups (n = 91) were significantly less likely to be virally suppressed at 6 months (53.1% and 49.3%) than comparisons (74.8% and 82.1%; p = 0.02 and p<0.0001, respectively). At 12 months only children in the ritonavir group still had lower rates of virological suppression relative to comparisons (63.9% vs 83.3% p<0.05). Grade 1 or greater ALT elevations were more common in the super-boosted (75%) than double-dose (54.6%) or ritonavir (33.9%) groups (p = 0.09 and p<0.0001) but grade 3/4 elevations were observed in 3 (13.6%) of the super-boosted, 7 (15.9%) of the double-dose and 5 (8.9%) of the ritonavir group (p = 0.81 and p = 0.29).

Conclusion

Good short-term virologic outcomes were achieved in children co-treated for TB and HIV who received super-boosted LPV/r. Treatment limiting toxicity was rare. Strategies for increased dosing of LPV/r with TB treatment warrant further investigation.     

Epidemiologic behavior of obesity in the Maracaibo City metabolic syndrome prevalence study

Introduction

Obesity is a worldwide public health issue. Since the epidemiological behaviour of this disease is not well established in our country, the purpose of this study was to determinate its prevalence in the Maracaibo City, Zulia State- Venezuela.

Materials and Methods

A cross-sectional study was undertaken using the data set from the Maracaibo City Metabolic Syndrome Prevalence Study. The sample consists of 2108 individuals from both genders and randomly selected: 1119 (53.09%) women and 989 (46.91%) men. The participants were interrogated for a complete clinical history and anthropometric measurements. To classify obesity, the WHO criteria for Body Mass Index (BMI), and Waist Circumference (WC) from the IDF/NHLBI/AHA/WHF/IAS/IASO-2009 (IDF-2009) and ATPIII statements were applied.

Results

For BMI, obesity had an overall prevalence of 33.3% (n = 701), and according to gender women had 32.4% (n = 363) and men had 34.2% (n = 338). Overweight had a prevalence of 34.8% (n = 733), Normal weight had 29.8% (n = 629), and Underweight had 2.1% (n = 45). Adding Obesity and Overweight results, the prevalence of elevated BMI (>25 Kg/m²) was 68.1%. Using the IDF-2009 WC''s cut-off, Obesity had 74.2% prevalence, compared to 51.7% using the ATPIII parameters.

Conclusions

These results show a high prevalence of abdominal obesity in our locality defined by the WHO, IDF-2009 and ATPIII criteria, which were not designed for Latin-American populations. We suggest further investigation to estimate the proper values according to ethnicity, genetic background and sociocultural aspects.     

Risk behaviors and reasons for not getting tested for HIV among men who have sex with men: an online survey in Peru

Background

Men who have sex with men (MSM) account for the greatest burden of the HIV epidemic in Peru. Given that MSM are frequent users of the Internet, understanding the risk behaviors and the reasons for not getting tested among MSM who surf the Internet may improve the tailoring of future online behavioral interventions.

Methods

From October 2007 to April 2008, we conducted an online survey among users of seven Peruvian gay websites.

Results

We received 1,481 surveys, 1,301 of which were included in the analysis. The median age of the participants was 22.5 years (range 12 – 71), 67% were homosexual, and the remainder was bisexual. Of survey respondents, 49.4% had never been tested for HIV and only 11.3% were contacted in-person during the last year by peer health educators from the Peruvian Ministry of Health and NGOs. Additionally, 50.8% had unprotected anal or vaginal sex at last intercourse, and a significant percentage reported a condom broken (22.1%), slipped (16.4%) or sexual intercourse initiated without wearing a condom (39.1%). The most common reasons for not getting tested for HIV among high-risk MSM were “I fear the consequences of a positive test result” (n = 55, 34.4%), and “I don''t know where I can get tested” (n = 50, 31.3%).

Conclusions

A small percentage of Peruvian MSM who answered our online survey, were reached by traditional peer-based education programs. Given that among high-risk MSM, fear of a positive test result and lack of awareness of places where to get tested are the most important reasons for not taking an HIV test, Internet interventions aimed at motivating HIV testing should work to reduce fear of testing and increase awareness of places that offer free HIV testing services to MSM.