Comparison of two doses of leucovorin in severe low-dose methotrexate toxicity - a randomized controlled trial.

BACKGROUND: Leucovorin (folinic acid) is a commonly used antidote for severe toxicity with low-dose methotrexate, but its optimum dose is unclear, varying from 15 to 25 mg every 6-h. METHODS: Open-label RCT included patients with severe low-dose (≤ 50 mg/week) methotrexate toxicity defined as WBC ≤ 2 × 10^9/L or platelet ≤ 50 × 10^9/L and randomized them to receive either usual (15 mg) or high-dose (25 mg) intravenous leucovorin given every 6-h. Primary outcome was mortality at 30-days and secondary outcomes were hematological recovery and mucositis recovery. TRIAL REGISTRATION NUMBER: CTRI/2019/09/021152. RESULTS: Thirty-eight patients were included, most with underlying RA who had inadvertently overdosed MTX (taken daily instead of weekly). At randomization, the median white blood and platelet count were 0.8 × 10^9/L and 23.5 × 10^9/L. 19 patients each were randomized to receive either usual or high-dose leucovorin. Number (%) of deaths over 30-days was 8 (42) and 9 (47) in usual and high-dose leucovorin groups (Odds ratio 1.2, 95% CI 0.3 to 4.5, p = 0.74). On Kaplan-Meier, there was no significant difference in survival between the groups (hazard ratio 1.1, 95% CI 0.4 to 2.9, p = 0.84). On multivariable cox-regression, serum albumin was the only predictor of survival (hazard ratio 0.3, 95% CI 0.1 to 0.9, p = 0.02). There was no significant difference in hematological or mucositis recovery between the two groups. CONCLUSION: There was no significant difference in survival or time-to hematological recovery between the two doses of leucovorin. Severe low-dose methotrexate toxicity carried a significant mortality.

Correlation of serum vitamin D levels with severity of pediatric atopic dermatitis and the impact of vitamin D supplementation on treatment outcomes.

INTRODUCTION: There is scarcity of prospective studies assessing the correlation between vitamin D deficiency and atopic dermatitis (AD). MATERIALS AND METHODS: We conducted a prospective study where in serum 25-hydroxy-vitamin D levels were measured in 35 AD patients and 35 age and sex-matched controls. AD patients deficient in vitamin D were supplemented with 1000 IU of vitamin D per day for three months. Serum vitamin D levels and SCORAD were again measured at the end of three months in all AD patients. RESULTS: The baseline vitamin D levels in patients and controls did not have any statistically significant difference (p = .97). There was a statistically significant (p = .02) inverse relationship between the AD severity and serum vitamin D levels at baseline (r = -0.52). Maximum reduction in SCORAD (41.4 ± 12.7) after 3 months of vitamin D supplementation was seen in severe AD and the minimum (2.4 ± 13.2) in mild AD (p = .0003). CONCLUSIONS: We found no difference in the mean serum vitamin D levels between AD patients and controls. An inverse correlation was seen between serum vitamin D levels at baseline and severity of AD. Beneficial effect of vitamin D supplementation was observed maximally in severe AD as observed by a reduction in SCORAD.

Comparison of effectiveness and safety of excimer lamp vs topical calcipotriol-clobetasol propionate combination in the treatment of palmoplantar psoriasis.

BACKGROUND: Very few studies have assessed the efficacy of excimer in the treatment of palmoplantar psoriasis (PPP), and none has compared the excimer with calcipotriol-clobetasol propionate combination. PURPOSE: To compare the effectiveness and safety of excimer lamp vs topical ointment containing calcipotriol (0.005% w/w) and clobetasol propionate (0.05% w/w) combination in PPP. METHODS: This right-left randomization trial included 36 patients with PPP, who received treatment with excimer lamp (twice weekly) on one side and calcipotriol-clobetasol combination (once daily) on another side for 12 weeks, followed by 8 weeks of follow-up. Recruitment and response assessment was done by 2 experienced dermatologists (SD and TN) using modified palmoplantar pustular psoriasis area and severity index score (mPPPASI, originally devised for palmoplantar pustulosis, suitably modified to assess response in PPP). Primary outcome measure was percentage improvement in mPPPASI at 12 weeks, which was classified as minimal (≤25%), mild (>25%-50%), moderate (>50%-75%), and marked (>75%). Secondary outcome measures were the proportion of patients achieving >75% reduction in mPPPASI and the time taken to achieve it. RESULTS: Of 36 recruited patients, 33 completed treatment and 21 adhered to 8-weeks follow-up. The mean mPPPASI on the excimer-treated sides reduced significantly from 7.75 ± 4.62 to 4.01 ± 4.07 (P < .001) at 12th week (end of the treatment) and 2.66 ± 3.97 at 20th week (at 8 weeks follow-up). The mean mPPPASI on the calcipotriol-clobetasol combination treated sides reduced significantly from 7.36 ± 4.46 to 3.55 ± 3.77 (P < .001) and 2.70 ± 3.97 at 12th week and 20th week, respectively. The reduction was significant for both treatment and the difference between the two was not statistically significant. Minimal, mild, moderate, and marked improvement was seen in 5/33 (15.2%) and 1/33 (3.0%), 6/33 (18.2%) and 8/33 (24.2%), 12/33 (36.4%) and 13/33 (39.4%), and 8/33 (24.2%) and 8/33 (24.2%) sides in the excimer and calcipotriol-clobetasol combination, respectively. A total of 8 patients in each group achieved mPPPASI 75 at 12 weeks. The mPPPASI 75 was achieved at 2, 4, and 8 weeks in 1, 2, and 8 patients, respectively, using either modalities. The adverse effects (most commonly hyperpigmentation) were noted more frequently on the excimer-treated sides; however, they were well tolerated. CONCLUSION: Both excimer lamp and calcipotriol-clobetasol propionate combination are equally effective in the treatment of PPP.

Leprosy--evolution of the path to eradication.

Leprosy is among the world's oldest and most dreaded diseases and it has been synonymous with stigma and discrimination due to the hideous deformities it produced, mystery around its aetiology and transmission and lack of any effective remedy till recently. Leprosy control started with the use of chaulmoogra oil and for the last three decades, multi drug therapy (MDT) has been our main tool against leprosy. In the last two decades, the reported global prevalence of active leprosy infection has dropped by almost 90 per cent by the combined efforts of the World Health Organization (WHO), local governments, health professionals, and non-governmental organizations (NGOs), however, a parallel drop in the incidence or new case detection rate (NCDR) has not occurred. From 1994 through 2011, more than 100,000 new cases are being detected annually, of whom maximum case load is from India. There is need for research on tools for early diagnosis, short and effective treatment, and prevention of deformities and disabilities. Evaluating the role of immunotherapy and immunoprophylaxis will also lead us to better understanding of their mode of action. Further molecular analysis of Mycobacterium leprae genome may provide the requisite basis for all this. The current reality is that there is a need to sustain and provide quality leprosy services to all persons through general health services, including good referral system. All these provisions in the integrated health care approach will go a long way in further reducing the stigma. Efforts need to be made to reduce deformity through early detection, self care, physiotherapy and reconstructive surgery and developing sound surveillance systems. With all the remarkable achievements in the fight against leprosy, the stage is now set for the final assault. It is hoped that with the efforts of all the stake holders and strong political will, the disease will be eradicated in the near future.