Utility of the Framingham risk score to predict the presence of coronary atherosclerosis in patients with rheumatoid arthritis

The prevalence of ischemic heart disease and atherosclerosis is increased in patients with rheumatoid arthritis (RA). In the general population, but not in patients with systemic lupus erythematosus, the Framingham risk score identifies patients at increased cardiovascular risk and helps determine the need for preventive interventions. We examined the hypothesis that the Framingham score is increased and associated with coronary-artery atherosclerosis in patients with RA. The Framingham score and the 10-year cardiovascular risk were compared among 155 patients with RA (89 with early disease, 66 with long-standing disease) and 85 control subjects. The presence of coronary-artery calcification was determined by electron-beam computed tomography. The Framingham score was compared in patients with RA and control subjects, and the association between the risk score and coronary-artery calcification was examined in patients. Patients with long-standing RA had a higher Framingham score (14 [11 to 18]) (median [interquartile range]) compared to patients with early RA (11 [8 to 14]) or control subjects (12 [7 to 14], P < 0.001). This remained significant after adjustment for age and gender (P = 0.015). Seventy-six patients with RA had coronary calcification; their Framingham risk score was higher (14 [12 to 17]) than that of 79 patients without calcification (10 [5 to 14]) (P < 0.001). Furthermore, a higher Framingham score was associated with a higher calcium score (odds ratio [OR] = 1.20, 95% confidence interval [CI] 1.12 to 1.29, P < 0.001), and the association remained significant after adjustment for age and gender (OR = 1.15, 95% CI 1.02 to 1.29, P = 0.03). In conclusion, a higher Framingham risk score is independently associated with the presence of coronary calcification in patients with RA.     

The impact of asymptomatic helminth co-infection in patients with newly diagnosed tuberculosis in north-west ethiopia

Background

Areas endemic of helminth infection, tuberculosis (TB) and HIV are to a large extent overlapping. The aim of this study was to assess the impact of asymptomatic helminth infection on the immunological response among TB patients with and without HIV, their house hold contacts and community controls.

Methodology

Consecutive smear positive TB patients (n = 112), their household contacts (n = 71) and community controls (n = 112) were recruited in Gondar town, Ethiopia. Stool microscopy, HIV serology, serum IgE level, eosinophil and CD4 counts were performed and tuberculosis patients were followed up for 3 months after initiation of anti-TB treatment.

Results

Helminth co-infection rate was 29% in TB patients and 21% in both community control and household contacts (p = 0.3) where Ascaris lumbricoides was the most prevalent parasite. In TB patients the seroprevalence of HIV was 47% (53/112). Eosinophilia and elevated IgE level were significantly associated with asymptomatic helminth infection. During TB treatment, the worm infection rate of HIV+/TB patients declined from 31% (10/32) at week 0 to 9% (3/32) at week 2 of TB treatment, whereas HIV−/TB patients showed no change from baseline to week 2, 29% (13/45) vs. 22.2% (10/45). This trend was stable at week 8 and 12 as well.

Conclusion

One third of smear positive TB patients were infected with helminths. Eosinophilia and elevated IgE level correlated with asymptomatic worm infection, indicating an effect on host immunity. The rate of worm infection declined during TB treatment in HIV+/TB co-infected patients whereas no decline was seen in HIV−/TB group.     

Independent and Joint Effects of Prenatal Zinc and Vitamin A Deficiencies on Birthweight in Rural Sidama,Southern Ethiopia: Prospective Cohort Study

Background

The effects of prenatal Zinc Deficiency (ZD) and Vitamin A Deficiency (VAD) on birthweight are controversial and their interaction has not been investigated.

Objective

To assess the independent and interaction effects of prenatal zinc and vitamin A deficiencies on birthweight in rural Sidama, Southern Ethiopia.

Methodology

A community-based prospective cohort study design was employed. Six hundred fifty pregnant women in their second or third trimester were randomly selected and their serum zinc and retinol concentrations were determined. About 575 subjects were successfully followed until delivery and birthweight was measured within 72 hours after delivery. The association between the exposures and birthweight was examined using log-binomial and liner regression analyses. Potential interaction between ZD and VAD was examined using Synergy Index (SI).

Results

The mean birthweight (± standard deviation) was 2896 g (±423). About 16.5% (95% CI: 13.5–19.6%) of the babies had Low Birthweight (LBW). Prenatal ZD and VAD were not significantly associated to LBW with Adjusted Relative Risk (ARR) of 1.25 (95 CI: 0.86–1.82) and 1.27 (95% CI: 0.86–1.87), respectively. Stratified analysis on the basis of gestational trimester showed that the occurrence of the deficiencies neither in the second nor third trimester were associated to LBW. The deficiencies did not show synergetic interaction in causing LBW [SI = 1.04 (95% CI: 0.17–6.28)]. Important risk factors of LBW were maternal illiteracy [RR = 1.80 (95% CI: 1.11–2.93)], female sex of the newborn [RR = 1.79 (95% CI: 1.19–2.67)], primiparity [RR = 1.16 (95% CI: 1.02–1.35)], short maternal stature [RR = 1.63 (95% CI: 1.06–2.51)] and maternal thinness [RR = 1.52 (95% CI: 1.03–2.25)]. In the linear regression model, elevated CRP was also negatively associated to birthweight.

Conclusion

LBW is of public health significance in the locality. The study did not witness any independent or interaction effect of prenatal ZD and VAD on birthweight.     

Using urine metabolomics to understand the pathogenesis of infant respiratory syncytial virus (RSV) infection and its role in childhood wheezing

Background

Respiratory syncytial virus (RSV) infection in infants causes significant morbidity and is the strongest risk factor associated with asthma. Metabolites, which reflect the interactions between host cell and virus, provide an opportunity to identify the pathways that underlie severe infections and asthma development.

Objective

To study metabolic profile differences between infants with RSV infection, and human rhinovirus (HRV) infection, and healthy infants. To compare infant metabolic differences between children who do and do not wheeze.

Methods

In a term birth cohort, urine was collected while healthy and during acute viral respiratory infection with RSV and HRV. We used ¹H-NMR to identify urinary metabolites. Multivariate and univariate statistics were used to discriminate metabolic profiles of infants with either RSV ARI, or HRV ARI, and healthy infants. Multivariable logistic regression was used to assess the association of urine metabolites with 1st-, 2nd-, and 3rd-year recurrent wheezing.

Results

Several metabolites in nicotinate and nicotinamide metabolism pathways were down-regulated in infants with RSV infection compared to healthy controls. There were no significant differences in metabolite profiles between infants with RSV infection and infants with HRV Infection. Alanine was strongly associated with reduced risk of 1st-year wheezing (OR 0.18[0.0, 0.46]) and 2nd-year wheezing (OR 0.31[0.13, 0.73]), while 2-hydroxyisobutyric acid was associated with increased 3rd-year wheezing (OR 5.02[1.49, 16.93]) only among the RSV infected subset.

Conclusion

The metabolites associated with infant RSV infection and recurrent-wheezing are indicative of viral takeover of the cellular machinery and resources to enhance virulence, replication, and subversion of the host immune-response, highlighting metabolic pathways important in the pathogenesis of RSV infection and wheeze development.

     

Setting up a pragmatic clinical trial in a low-resource setting: A qualitative assessment of GoLBeT,a trial of podoconiosis management in Northern Ethiopia

BackgroundClinical trials are often perceived as being expensive, difficult and beyond the capacity of healthcare workers in low-resource settings. However, in order to improve healthcare coverage, the World Health Organization (WHO) World Health Report 2013 stated that all countries need to become generators as well as recipients of data. This study is a methodological examination of the steps and processes involved in setting up the Gojjam Lymphoedema Best Practice Trial (GoLBeT; ISRCTN67805210), a highly pragmatic clinical trial conducted in northern Ethiopia. Challenges to the trial and strategies used to deal with them were explored, together with the reasons for delays.Methodology and principal findingsQualitative research methods were used to analyse emails and reports from the period between trial inception and recruitment. This analysis was complemented by interviews with key informants from the trial operational team. The Global Health Research Process Map was used as a framework against which to compare the steps involved in setting up the trial. A mini-group discussion was conducted with the trial operational team after study completion for reflection and further recommendations.This study showed that the key areas of difficulty in setting up and planning this trial were: the study design, that is, deciding on the study endpoint, where and how best to measure it, and assuring statistical power; recruitment and appropriate training of staff; planning for data quality; and gaining regulatory approvals. Collaboration, for example with statisticians, the trial steering committee, the study monitors, and members of the local community was essential to successfully setting up the trial.Conclusions and significanceLessons learnt from this trial might guide others planning pragmatic trials in settings where research is not common, allowing them to anticipate possible challenges and address them through trial design, planning and operational delivery. We also hope that this example might encourage similar pragmatic studies to be undertaken. Such studies are rarely undertaken or locally led, but are an accessible and efficient way to drive improved outcomes in public health.     

The inhibition of tryptophan hydroxylase, not protein synthesis, reduces the brain trapping of α-methyl-l-tryptophan: an autoradiographic study

The effects of the tryptophan hydroxylase (TPH) inhibitor p-chlorophenylalanine (PCPA; 200mg/kg; 3 days), and of the protein synthesis inhibitor cycloheximide (CXM, 2mg/kg), on regional serotonin (5-HT) synthesis were studied using the alpha-[14C]methyl-L-tryptophan (alpha-[14C]MTrp) autoradiographic method. The objectives of these investigations were to evaluate the changes, if any, on 5-HT synthesis, as measured with alpha-MTrp method, following the inhibition of TPH by PCPA, or the inhibition of proteins synthesis by CXM. The rats were used in the tracer experiment approximately 24h after the last dose of PCPA was administered, and in the CXM experiments, they were used 30 min following a single injection of CXM. In both experiments, the control rats were injected with the same volume of saline (0.5 ml/kg; s.c.) and at the same times as the drug injections. The results demonstrate that trapping of alpha-MTrp, which is taken to be related to brain 5-HT synthesis, is drastically reduced (40-80%) following PCPA treatment. The inhibition of protein synthesis with CXM did not have a significant effect on the global brain trapping of alpha-MTrp and 5-HT synthesis. These findings suggest that the brain trapping of alpha-[14C]MTrp relates to brain 5-HT synthesis, but not to brain protein synthesis.     

Use of Pentamidine As Secondary Prophylaxis to Prevent Visceral Leishmaniasis Relapse in HIV Infected Patients,the First Twelve Months of a Prospective Cohort Study

Background

Visceral leishmaniasis (VL) has become an important opportunistic infection in persons with HIV-infection in VL-endemic areas. The co-infection leads to profound immunosuppression and high rate of annual VL recurrence. This study assessed the effectiveness, safety and feasibility of monthly pentamidine infusions to prevent recurrence of VL in HIV co-infected patients.

Methods

A single-arm, open-label trial was conducted at two leishmaniasis treatment centers in northwest Ethiopia. HIV-infected patients with a VL episode were included after parasitological cure. Monthly infusions of 4mg/kg pentamidine-isethionate diluted in normal-saline were started for 12months. All received antiretroviral therapy (ART). Time-to-relapse or death was the primary end point.

Results

Seventy-four patients were included. The probability of relapse-free survival at 6months and at 12 months was 79% and 71% respectively. Renal failure, a possible drug-related serious adverse event, occurred in two patients with severe pneumonia. Forty-one patients completed the regimen taking at least 11 of the 12 doses. Main reasons to discontinue were: 15 relapsed, five died and seven became lost to follow-up. More patients failed among those with a CD4+cell count ≤ 50cells/μl, 5/7 (71.4%) than those with counts above 200 cells/μl, 2/12 (16.7%), (p = 0.005).

Conclusion

Pentamidine secondary prophylaxis led to a 29% failure rate within one year, much lower than reported in historical controls (50%-100%). Patients with low CD4+cell counts are at increased risk of relapse despite effective initial VL treatment, ART and secondary prophylaxis. VL should be detected and treated early enough in patients with HIV infection before profound immune deficiency installs.