Efficacy of Methotrexate in Combination with Antioxidant Vitamins (A, C & E) versus Methotrexate alone in the Treatment of Rheumatoid Arthritis

Background: There is evidence that oxidative stress plays an important role in autoimmune diseases, such as rheumatoid arthritis (RA). Despite the supporting evidence for a beneficial effect of antioxidants on clinical characteristics of RA, the right balance for optimal effectiveness of antioxidants is largely unknown. A study was designed to determine the potential beneficial effects of antioxidant intervention on clinical parameters of RA.Methods: Randomized clinical trial of 152 patients with positive rheumatoid factor (RF) and a Disease Activity Score (DAS 28) higher than 3.2 were enrolled in the study. Patients were divided into two groups (Group A and Group B) randomly and group A received methotrexate and antioxidant vitamins (A, C and E in a fixed dose) and group B methotrexate only. They were followed up for three visits (baseline, 10th week and 14th week). The intervention was stopped after 10 weeks and was followed by a ‘wash-out’ period of 4 weeks. At baseline, 10th week and 14th week patient’s condition were assessed by means of DAS-28 score. P- Value less than <0.05 was considered significant.Results: The numbers of swollen and tender joints were significantly reduced and general health was improved reflected by improved DAS-28 score at 10th week.The antioxidant effect was considered beneficial as compared to the scores of 1st visit at baseline; the DAS-28 score was significantly reduced at 2nd visit at 10th week. Increment of the DAS-28 score among the group A patients who were on antioxidant up to10 weeks, after the “wash-out period” of four weeks i.e. at 14th week confirmed a significant relation between changes in clinical condition and antioxidants.Conclusion: This study was designed to assess the potential beneficial effect of antioxidants (Vitamin A, C and E) in combination with methotrexate in the treatment of RA

Malarial Retinopathy in Bangladeshi Adults

To establish if assessment of malarial retinopathy in adult malaria using ophthalmoscopy by non-ophthalmologists has clinical and prognostic significance, 210 Bangladeshi adults were assessed by both direct and indirect ophthalmoscopy; 20 of 20 healthy subjects and 20 of 20 patients with vivax malaria showed no retinal changes, whereas in patients with falciparum malaria, indirect ophthalmoscopy revealed malarial retinopathy (predominantly retinal hemorrhages) in 18 of 21 (86%) fatal, 31 of 75 (41%) cerebral, 16 of 64 (25%) non-cerebral but severe, and 1 of 31 (3%) uncomplicated cases. Direct ophthalmoscopy missed retinopathy in one of these cases and found fewer retinal hemorrhages (mean difference = 3.09; 95% confidence interval = 1.50–4.68; P < 0.0001). Severity of retinopathy increased with severity of disease (P for trend < 0.0001), and renal failure, acidosis, and moderate/severe retinopathy were independent predictors of mortality by both ophthalmoscopic techniques. Direct ophthalmoscopy by non-ophthalmologists is an important clinical tool to aid diagnosis and prognosis in adults with severe malaria, and indirect ophthalmoscopy by non-ophthalmologists, although more sensitive, provides minimal additional prognostic information

Timing of Enteral Feeding in Cerebral Malaria in Resource-Poor Settings: A Randomized Trial

BACKGROUND: Early start of enteral feeding is an established treatment strategy in intubated patients in intensive care since it reduces invasive bacterial infections and length of hospital stay. There is equipoise whether early enteral feeding is also beneficial in non-intubated patients with cerebral malaria in resource poor settings. We hypothesized that the risk of aspiration pneumonia might outweigh the potential benefits of earlier recovery and prevention of hypoglycaemia. METHOD AND FINDINGS: A randomized trial of early (day of admission) versus late (after 60 hours in adults or 36 hours in children) start of enteral feeding was undertaken in patients with cerebral malaria in Chittagong, Bangladesh from May 2008 to August 2009. The primary outcome measures were incidence of aspiration pneumonia, hypoglycaemia and coma recovery time. The trial was terminated after inclusion of 56 patients because of a high incidence of aspiration pneumonia in the early feeding group (9/27 (33%)), compared to the late feeding group (0/29 (0%)), p = 0.001). One patient in the late feeding group, and none in the early group, had hypoglycaemia during admission. There was no significant difference in overall mortality (9/27 (33%) vs 6/29 (21%), p = 0.370), but mortality was 5/9 (56%) in patients with aspiration pneumonia. CONCLUSIONS: In conclusion, early start of enteral feeding is detrimental in non-intubated patients with cerebral malaria in many resource-poor settings. Evidence gathered in resource rich settings is not necessarily transferable to resource-poor settings. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN57488577

Laboratory prediction of the requirement for renal replacement in acute falciparum malaria

BACKGROUND: Acute renal failure is a common complication of severe malaria in adults, and without renal replacement therapy (RRT), it carries a poor prognosis. Even when RRT is available, delaying its initiation may increase mortality. Earlier identification of patients who will need RRT may improve outcomes. METHOD: Prospectively collected data from two intervention studies in adults with severe malaria were analysed focusing on laboratory features on presentation and their association with a later requirement for RRT. In particular, laboratory indices of acute tubular necrosis (ATN) and acute kidney injury (AKI) that are used in other settings were examined. RESULTS: Data from 163 patients were available for analysis. Whether or not the patients should have received RRT (a retrospective assessment determined by three independent reviewers) was used as the reference. Forty-three (26.4%) patients met criteria for dialysis, but only 19 (44.2%) were able to receive this intervention due to the limited availability of RRT. Patients with impaired renal function on admission (creatinine clearance < 60 ml/min) (n = 84) had their laboratory indices of ATN/AKI analysed. The plasma creatinine level had the greatest area under the ROC curve (AUC): 0.83 (95% confidence interval 0.74-0.92), significantly better than the AUCs for, urinary sodium level, the urea to creatinine ratio (UCR), the fractional excretion of urea (FeUN) and the urinary neutrophil gelatinase-associated lipocalcin (NGAL) level. The AUC for plasma creatinine was also greater than the AUC for blood urea nitrogen level, the fractional excretion of sodium (FeNa), the renal failure index (RFI), the urinary osmolality, the urine to plasma creatinine ratio (UPCR) and the creatinine clearance, although the difference for these variables did not reach statistical significance. CONCLUSIONS: In adult patients with severe malaria and impaired renal function on admission, none of the evaluated laboratory indices was superior to the plasma creatinine level when used to predict a later requirement for renal replacement therapy

Central venous catheter use in severe malaria: time to reconsider the World Health Organization guidelines?

<p>Abstract</p> <p>Background</p> <p>To optimize the fluid status of adult patients with severe malaria, World Health Organization (WHO) guidelines recommend the insertion of a central venous catheter (CVC) and a target central venous pressure (CVP) of 0-5 cmH₂O. However there are few data from clinical trials to support this recommendation.</p> <p>Methods</p> <p>Twenty-eight adult Indian and Bangladeshi patients admitted to the intensive care unit with severe <it>falciparum </it>malaria were enrolled in the study. All patients had a CVC inserted and had regular CVP measurements recorded. The CVP measurements were compared with markers of disease severity, clinical endpoints and volumetric measures derived from transpulmonary thermodilution.</p> <p>Results</p> <p>There was no correlation between the admission CVP and patient outcome (p = 0.67) or disease severity (p = 0.33). There was no correlation between the baseline CVP and the concomitant extravascular lung water (p = 0.62), global end diastolic volume (p = 0.88) or cardiac index (p = 0.44). There was no correlation between the baseline CVP and the likelihood of a patient being fluid responsive (p = 0.37). On the occasions when the CVP was in the WHO target range patients were usually hypovolaemic and often had pulmonary oedema by volumetric measures. Seven of 28 patients suffered a complication of the CVC insertion, although none were fatal.</p> <p>Conclusion</p> <p>The WHO recommendation for the routine insertion of a CVC, and the maintenance of a CVP of 0-5 cmH₂O in adults with severe malaria, should be reconsidered.</p