Peak oxygen intake and cardiac mortality in women referred for cardiac rehabilitation

OBJECTIVES: This study investigated the prognostic importance of measured peak oxygen intake (VO(2peak)) in women with known coronary heart disease referred for outpatient cardiac rehabilitation. BACKGROUND: Exercise capacity is a powerful predictor of prognosis in men with known or suspected coronary disease. Similar findings are described in women, but fewer studies have utilized measured VO(2peak), the most accurate measure of exercise capacity. METHODS: A single-center design took data from 2,380 women, age 59.7 +/- 9.5 years (1,052 myocardial infarctions, 620 coronary bypass procedures, and 708 with proven ischemic heart disease), who underwent cardiorespiratory exercise testing. They were followed for an average of 6.1 +/- 5 years (median 4.5 years, range 0.4 to 25 years) until cardiac and all-cause death. RESULTS: We recorded 95 cardiac deaths and 209 all-cause deaths. Measured VO(2peak) was an independent predictor of risk, values > or =13 ml/kg/min (3.7 multiples of resting metabolic rate) conferring a 50% reduction in cardiac mortality (hazard ratio [HR] 0.5, p = 0.001). Considered as a continuous variable, a 1 ml/kg/min advantage in initial VO(2peak) was associated with a 10% lower cardiac mortality. Adverse predictors were diabetes (HR 2.73, p = 0.0005) and antiarrhythmic therapy (HR 3.93, p = 0.0001). CONCLUSIONS: As in men, measured VO(2peak) is a strong independent predictor of cardiac mortality in women referred for cardiac rehabilitation.     

Intravascular ultrasound assessment of the effect of laser energy on the arterial wall during the treatment of femoro-popliteal lesions: a CliRpath excimer laser system to enlarge lumen openings (CELLO) registry study

The CliRpath Excimer Laser System to Enlarge Lumen Openings (CELLO) registry included patients treated with modified excimer laser catheters for the endovascular treatment of peripheral artery disease affecting the superficial femoral artery (SFA) and proximal popliteal artery. The aim of this study was to assess, via intravascular ultrasound (IVUS) the dissections in the vessel wall following treatment with the laser catheters. IVUS grayscale images from the CELLO registry were systematically reviewed for dissections in the treated vessel segments by two investigators. Images from 33 patients; 66 pullbacks (1867 IVUS frames in 2 phases), were successfully matched frame-to-frame to evaluate identical segments of the treated vessels in the two phases; post-2 mm Turbo-Elite laser pilot channel creation and post Turbo-Booster laser atherectomy. Dissections were categorized as; (1) intimal, (2) medial, (3) intramural hematoma, and (4) adventitial according to the ACC Clinical Expert Consensus Document classification of dissections. An average of 57 frames was evaluated per pullback, giving a total of 3734 frames (1867 matched for pre-ablation (post channel creation) and post-ablation phases). Treatments with the modified Excimer laser catheters resulted in a significant increase in lumen area of 5.5?±?3.2-mm² (95% CI 4.3–6.8, p?<?0.0001) and reduction in plaque plus media volume of ?10.6?±?36.0 mm³ (95% CI ?25.8 to 4.6, p?=?0.1619) whilst giving rise to mainly intramural hematoma formations post Turbo-Booster laser treatment in 55% of frames assessed and 24% medial dissections with less than 1% adventitial disruption. The Excimer laser based Turbo-Booster treatment of peripheral artery lesions resulted in significant plaque debulking and increased lumen diameter with negligible degree of adventitial layer injury.     

Defaulters from antiretroviral treatment in Jimma University Specialized Hospital, Southwest Ethiopia

Objective To determine the prevalence of and factors associated with defaulting from antiretroviral treatment (ART) in Jimma, Ethiopia. Methods Unmatched case control study: cases were individuals who had missed two or more clinical appointments (i.e. had not been seen for the last 2 months) between January 2005 and February 2007; controls were individuals who had been on ART at least for 1 year and were rated as excellent adherers by the providers. Data were collected from patient records, and by telephone call and home visit to identify the reason for defaulting. Results Of 1270 patients who started ART, 915 (72.0%) were active ART users and 355 (28.0%) had missed two or more clinical appointments. The latter comprised 173 (13.6%) defaulters, 101 (8.0%) who transferred out, 75 (5.9%) who died, and 6 (0.5%) who restarted ART. Reasons for defaulting were unclear in most cases. Reasons given were loss of hope in medication, lack of food, mental illness, holy water, no money for transport, and other illnesses. Tracing was not successful because of incorrect address on the register in 61.6% of the cases. Taking hard drugs (cocaine, cannabis and IV drugs), excessive alcohol consumption, being bedridden, living outside Jimma town and having an HIV negative or unknown HIV status partner were associated with defaulting ART. Conclusion A significant proportion of patients defaulted from ART treatment. ART clinics should ensure that patients’ addresses are correct and complete. Programmatic and counseling efforts to decrease ART defaulting should address illicit drug and excessive alcohol use, decentralise ART services, institute home‐based treatment options for seriously ill and bedridden patients, and address patients concerns.     

Impact of tuberculosis on mortality among HIV-infected patients receiving antiretroviral therapy in Uganda: a prospective cohort analysis

Background

Tuberculosis (TB) disease affects survival among HIV co-infected patients on antiretroviral therapy (ART). Yet, the magnitude of TB disease on mortality is poorly understood.

Methods

Using a prospective cohort of 22,477 adult patients who initiated ART between August 2000 and June 2009 in Uganda, we assessed the effect of active pulmonary TB disease at the initiation of ART on all-cause mortality using a Cox proportional hazards model. Propensity score (PS) matching was used to control for potential confounding. Stratification and covariate adjustment for PS and not PS-based multivariable Cox models were also performed.

Results

A total of 1,609 (7.52%) patients had active pulmonary TB at the start of ART. TB patients had higher proportions of being male, suffering from AIDS-defining illnesses, having World Health Organization (WHO) disease stage III or IV, and having lower CD4 cell counts at baseline (p?<?0.001). The percentages of death during follow-up were 10.47% and 6.38% for patients with and without TB, respectively. The hazard ratio (HR) for mortality comparing TB to non-TB patients using 1,686 PS-matched pairs was 1.37 (95% confidence interval [CI]: 1.08 – 1.75), less marked than the crude estimate (HR?=?1.74, 95% CI: 1.49 – 2.04). The other PS-based methods and not PS-based multivariable Cox model produced similar results.

Conclusions

After controlling for important confounding variables, HIV patients who had TB at the initiation of ART in Uganda had an approximate 37% increased hazard of overall mortality relative to non-TB patients.

     

Proof of concept study to develop a novel connectivity-based electric-field modelling approach for individualized targeting of transcranial magnetic stimulation treatment

Resting state functional connectivity (rsFC) offers promise for individualizing stimulation targets for transcranial magnetic stimulation (TMS) treatments. However, current targeting approaches do not account for non-focal TMS effects or large-scale connectivity patterns. To overcome these limitations, we propose a novel targeting optimization approach that combines whole-brain rsFC and electric-field (e-field) modelling to identify single-subject, symptom-specific TMS targets. In this proof of concept study, we recruited 91 anxious misery (AM) patients and 25 controls. We measured depression symptoms (MADRS/HAMD) and recorded rsFC. We used a PCA regression to predict symptoms from rsFC and estimate the parameter vector, for input into our e-field augmented model. We modeled 17 left dlPFC and 7 M1 sites using 24 equally spaced coil orientations. We computed single-subject predicted ΔMADRS/HAMD scores for each site/orientation using the e-field augmented model, which comprises a linear combination of the following elementwise products (1) the estimated connectivity/symptom coefficients, (2) a vectorized e-field model for site/orientation, (3) rsFC matrix, scaled by a proportionality constant. In AM patients, our connectivity-based model predicted a significant decrease depression for sites near BA9, but not M1 for coil orientations perpendicular to the cortical gyrus. In control subjects, no site/orientation combination showed a significant predicted change. These results corroborate previous work suggesting the efficacy of left dlPFC stimulation for depression treatment, and predict better outcomes with individualized targeting. They also suggest that our novel connectivity-based e-field modelling approach may effectively identify potential TMS treatment responders and individualize TMS targeting to maximize the therapeutic impact.Subject terms: Cognitive control, Depression     

Understanding the role of tumor stem cells in glioblastoma multiforme: a review article

It has been hypothesized that cancer stem cells (CSC) may account for the pathogenesis underlying various tumors, including GBM. Markers of these CSCs can be potentially used as therapeutic targets. In this review, we discuss the most recent information regarding CSCs, their molecular biology and their potential role in GBM.     

Prevalence of onchocercal skin disease and infection among workers of coffee plantation farms in Teppi,southwestern Ethiopia

In June 1996, a study on the economic impacts of onchocercal skin disease was initiated in southwestern Ethiopia. We made parasitological and clinicoepidemiological investigations among 1619 workers of a coffee plantation firm in Teppi, south-western Ethiopia. Sixty percent of the workers were included in the study. The prevalence of onchocercal skin disease (OSD) was 85.3%. Severe OSD (SOSD) was found in 17.3% of the study subjects. This was 1/5 of all OSD cases. The overall nodule carrier rate was 44.2%, which differed significantly by age classes from a rate of 12.3% to 73.0%. This rate varied by sex, 51.7% in males and 22.6% in females. Microfilarial carrier rate (MFCR) was 77.6%. This rate did not vary neither with severity of disease nor with presence or absence of pruritus or onchodermatitis. Mean microfilarial count was determined to be 38.1 per mg of skin snip or 44.4 per mg of infected skin snips. The geometric mean of microfilarial load per infected skin was 23.8. The community microfilarial load (CMFL) was estimated to be 14.0 per mg skin snip. The study showed that SOSD is prevalent in Teppi and affects a substantial number of the working population. An intervention program is called for.     

Hepatitis C virus envelope glycoproteins and potential for vaccine development

HCV envelope glycoproteins play an important role in the initiation of viral infection. The functional dichotomy of the individual HCV glycoproteins was investigated using VSV/HCV pseudotype virus. Surprisingly, VSV/HCV pseudotype virus generated from either E1 or E2 displayed infectivity of a number of mammalian cells. The use of pseudotyped virus has allowed us to better understand the similar and divergent properties of E1 and E2 glycoproteins decorating the envelope of HCV. The serum pseudotype virus neutralizing activity in patient sera did not exhibit a correlation with the infecting HCV genotype or virus load. HCV E2 glycoprotein induces a weak neutralizing antibody response, however the neutralization function was augmented by complement. Taken together, these observations suggest a role for both the glycoproteins in HCV attachment and entry into susceptible host cells. An understanding of HCV entry and strategies appropriate for mimicking cell surface molecules may help in the development of new therapeutic modalities against HCV infection. Furthermore, incorporation of the HCV glycoproteins in a candidate vaccine may offer protection, although additional work is necessary to enhance their immunogenicity.