Randomized Trial of Metformin With Anti-Tuberculosis Drugs for Early Sputum Conversion in Adults With Pulmonary Tuberculosis.

BACKGROUND: Metformin, by reducing intracellular Mycobacterium tuberculosis growth, can be considered an adjunctive therapy to anti-tuberculosis treatment (ATT). We determined whether metformin with standard ATT reduces time to sputum culture conversion and tissue inflammation in adults with pulmonary tuberculosis (PTB). METHODS: In a randomized, 8-week, clinical trial, newly diagnosed, culture-positive PTB patients were randomized to standard ATT (HREZ = control arm) or standard ATT plus daily 1000 mg metformin (MET-HREZ = Metformin with Rifampicin [METRIF] arm) for 8 weeks during 2018-2020 at 5 sites in India. The primary end point was time to sputum culture conversion by liquid culture during 8 weeks of ATT. Plasma inflammatory markers were estimated in a subset. A Cox proportional hazard model was used to estimate time and predictors of culture conversion. RESULTS: Of the 322 patients randomized, 239 (74%) were male, and 212 (66%) had bilateral disease on chest radiograph with 54 (18%) showing cavitation. The median time to sputum culture conversion by liquid culture was 42 days in the METRIF arm and 41 days in the control arm (hazard ratio, 0.8; 95% confidence interval [CI], .624-1.019). After 8 weeks of ATT, cavitary lesions on X-ray (7, 5.3% vs 18, 12.9%; relative risk, 0.42; 95% CI, .18-.96; P = .041) and inflammatory markers were significantly lower in the METRIF arm. Higher body mass index and lower sputum smear grading were associated with faster sputum culture conversion. CONCLUSIONS: The addition of metformin to standard ATT did not hasten sputum culture conversion but diminished excess inflammation, thus reducing lung tissue damage as seen by faster clearance on X-ray and reduced inflammatory markers. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry of India (CTRI/2018/01/011176).

Optimization of Human Semen Extender Components for Cryopreservation Using Statistical Tools.

　　BACKGROUND: Human sperm cell preservation is an important part of assisted reproductive technology (ART). OBJECTIVE: This study aimed to find the essential and significant components in semen preservation extender required to prolong the shelf life of human spermatozoa. MATERIALS AND METHODS: By using the statistical tool 'Plackett-Burman design' the significant components present in E4 extender (formulated in our previous study) was determined by reducing the unacceptable large number of trial experiments from the full factorial method. RESULTS: It was found that vitamin E, taurine and vitamin C were highly significant in maintaining the stability of sperm cells; and egg yolk, vitamin C and glucose were highly significant in sustaining the motility of the sperm cells. R2 values for the models were 0.9950 and 0.9960 respectively. In the optimized E4 extender 75 % and 81 % of the total motility was retained by the sperm cells from infertile and fertile samples respectively after cryopreservation. Also an increase in zeta potential was observed indicating a reduction in stability in both fertile and infertile sample (4 % and 18 % respectively) after cryopreservation in E4 medium, which was much less when compared with the sample preserved only with glycerol as cryoprotectant (11 % and 69 % for infertile and fertile samples respectively). CONCLUSION: The major components present in E4 semen extender was successfully optimized for further use.

Childhood cancer in developing society: A roadmap of health care.

BACKGROUND: We assessed referral patterns of children with hematological malignancies (HM) in North India. MATERIALS AND METHODS: The parents/guardians were interviewed at presentation, in the period between October 2001 and November 2002. Patient delay (symptom-contact), health system delay (contact-diagnosis), total delay (symptom-diagnosis), and number of contacts were compared between high- and standard-risk disease group. RESULTS: Of the 79 children (55 boys; 69.6%) with HM, 47 (59.5%) had Acute Lymphoblastic Leukemia (ALL). Forty-four children had high-risk disease. The patient, system and total delay were a median of 2 days (with Interquartile range IQR of 1-6), 37 days (IQR 13-55), and 38 days (IQR 15-60) respectively. Majority of patients (64/79; 81%) went to private sector (non governmental health care providers) for health care. Number of contacts, which was the most significant, correlate with system delay. CONCLUSIONS: Sensitizing the private sector practitioners about cancer in symptomatic children (pallor, bleeding, fever) may be effective.