Objectives: Convalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. Design: Open-label, parallel-arm, phase II, multicentre, randomized controlled trial. Setting: Thirty-nine public and private hospitals across India. Participants: Hospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 ≤ 93% on room air). Intervention: Participants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome Measure: Composite of progression to severe disease (PaO2/FiO2<100) or all-cause mortality at 28 days post-enrolment. Results: Between 22 nd April to 14 th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. Interpretation: CP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19.

Background and aimDengue fever is an emerging arboviral public health problem in a large endemic population in the tropical and sub-tropical areas of the world, with varying degrees of clinical presentation. This study was aimed at analyzing the clinical and laboratory dynamics of the four dengue serotypes. MethodsThis institutional review board (IRB)-approved hospital-based observational study was performed with 100 in-patients with dengue infection above 12 years of age, without co-morbidities or known malignancy, in a tertiary care center in Northern India. ResultsOut of 100 patients, four had concurrent infection with two serotypes. Dengue virus serotype-2 (DENV 2) was the most common serotype (34%) and had the maximum percentage of cases of severe dengue (20.6%). The mean total leukocyte count did not differ between the serotypes. DENV 4 had a significantly higher mean neutrophil percentage and a significantly lower mean lymphocyte percentage than DENV 1 (p-value 0.001 and 0.02, respectively), with a higher percentage of cases of severe dengue (20% vs 14.3%, nonsignificant). Thrombocytopenia was present in all serotypes of infection. There was a significant difference in the derangement of liver function in DENV 2, 3, and 4 as compared to DENV 1. Mean serum albumin levels were significantly lower in DENV 3 and 4 infections. Cases with co-infection had a much higher derangement of liver function and lower mean serum albumin than infections with a single serotype. The mean blood urea and creatinine levels were in the normal range for all serotypes. No mortality occurred in our study. ConclusionDENV 2 is the most common serotype with maximum severity at our hospital. DENV 2 and DENV 4 have a high percentage of cases with severe dengue (20.6% and 20%, respectively). The mean lymphocyte percentage was significantly lower while hepatic involvement and hypoalbuminemia were greater in DENV 4. Initial serotyping in patients with dengue can help monitor the epidemiological trends and help estimate the clinical and laboratory trends of the different serotypes of dengue infection. Particular care should be taken in patients with co-infection.

Leukotriene (LT) modifiers are anti-inflammatory drugs that are useful as an add-on therapy with first-line asthma-controller medications. This group includes LT synthesis inhibitors (eg, Zileuton) and receptor antagonists (eg, Montelukast), whose direct comparative clinical data are not available. This study was conducted to assess the comparative efficacy and safety of orally administered Zileuton extended-release (ER) with Montelukast sodium in patients suffering from chronic persistent asthma. Patients of 18-65 years of age with mild to moderate chronic stable asthma were randomized to treatment with Zileuton ER 2400 mg/d or Montelukast 10 mg/d for 12 weeks. Peak expiratory flow rate (PEFR) and asthma symptoms (cough, wheeze, chest tightness, and shortness of breath each on a 4-point scale) were assessed on monthly scheduled out-patient visits. Safety assessments by clinical and laboratory parameters were carried out during the course of the study. Among 210 patients eligible for efficacy assessment, PEFR improved by 64.8 ± 52.8 (95% confidence interval: 54.8-74.7) L/min with Zileuton ER (n = 109) and 40.6 ± 47.5 (31.3-49.9) L/min with Montelukast (n = 101; P < 0.001), whereas percent improvements were 27.0% (22.6%-31.5%) versus 18.4% (14.1%-22.7%), respectively (P = 0.006). Zileuton ER lead to ≥12% PEFR improvements in 74 of 109 [67.9% (59.1%-76.7%)] patients, whereas the same was noted in 52 of 101 [51.5% (41.7%-61.2%)] patients receiving Montelukast (P = 0.015). The reduction in the mean overall symptom intensity score was also significantly better with Zileuton ER [-5.0 ± 2.1 (4.6-5.4) versus -4.2 ± 2.3 (3.8-4.7)] (P = 0.018); however, the same was not observed for the decline in the individual symptom scores. A lesser but not significantly different adverse event rate was reported in the Zileuton ER group than the Montelukast group with the commonest events being headache and gastrointestinal effects in both the groups. Thus, Zileuton ER seems to be more efficacious than Montelukast and well tolerated for the treatment of mild to moderate chronic persistent asthma in adult patient population. Further studies can elucidate the comparative treatment benefits of these LT modifiers in asthma management.

A 30-year-old male jewellery factory worker accidentally ingested silver potassium cyanide and was brought to the emergency department in a state of shock and profound metabolic acidosis. This patient was managed hypothetically with use of injection thiopentone sodium intravenously until the antidote was received. Cyanide is a highly cytotoxic poison and it rapidly reacts with the trivalent iron of cytochrome oxidase thus paralysing the aerobic respiration. The result is severe lactic acidosis, profound shock, and its fatal outcome. The patient dies of cardio-respiratory arrest secondary to dysfunction of the medullary centres. It is rapidly absorbed, symptoms begin few seconds after exposure and death usually occurs in <30 min. The average lethal dose for potassium cyanide is about 250 mg. We used repeated doses of thiopentone sodium till the antidote kit was finally in our hands, hypothesising that it contains thiol group similar to the antidote thiosulphate. Moreover, it is an anticonvulsant. We were successful in our attempts and the patient survived though the specific antidotes could be administered after about an hour.

No abstract