Initiation of mycophenolate mofetil (MMF) treatment was not superior to placebo in maintaining myasthenia gravis (MG) control during a 36-week schedule of prednisone tapering. There were no significant differences in the primary or secondary endpoints between the study groups. MMF was well tolerated and adverse events were consistent with previous studies. Experience from this large, international, multicenter, phase III study employing full MG Foundation of America guidelines will aid the design of future MG studies.
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.
This study confirmed the prognostic importance of advancing age and the intensity of prodromal or acute pain as risk factors for prolonged zoster-associated pain and persisting abnormal sensations in the affected dermatome. Ophthalmic zoster and pre-existing neurological disorders are also identified as highly significant risk factors for prolonged abnormal sensations in herpes zoster.
Demographic and clinical characteristics of patients with herpes zoster at the time of presentation predict the duration and severity of pain on long-term follow-up. Analyses by Cox's proportional hazard models of six databases from controlled trials of antiviral drugs (total subjects = 2367) identified covariates for zoster-associated pain; all tests for significance were two-sided. Age strongly influenced pain outcome: patients > or = 50 years old were significantly more likely to have prolonged zoster-associated pain compared with those < 30 years old. Patients with prodromal symptoms or moderate or severe pain at presentation were also more likely to experience prolonged zoster-associated pain. Neither time to initiating treatment after rash onset nor sex of patient influenced pain outcome. Advancing age, prodromal symptoms, and acute pain severity at presentation predicted those individuals most at risk of prolonged pain and postherpetic neuralgia. When two or more of these factors were present, the risk of persistent pain was increased.
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