Clinical drug investigation
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Metformin has been associated with lactic acidosis. Lactate levels are not commonly tested in clinical practice, and it is unclear to what extent metformin would typically increase lactate levels with chronic use. The aim of this review was to determine whether regular monitoring of the plasma lactate level would be beneficial in avoiding lactate accumulation and, ultimately, minimising the incidence of lactic acidosis in metformin-treated patients. ⋯ However, most results showed that the lactate level remained in the normal range. No definitive conclusions on the benefits of regular lactate monitoring in patients taking metformin can be made. Future research on larger populations focusing on the measurement of lactate levels with continuous metformin use is warranted.
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Randomized Controlled Trial
A Randomized Trial to Assess the Effect of Doravirine on the QTc Interval Using a Single Supratherapeutic Dose in Healthy Adult Volunteers.
Doravirine is a novel HIV-1 non-nucleoside reverse transcriptase inhibitor exhibiting a robust safety and efficacy profile in combination with other antiretrovirals. While existing data do not suggest that doravirine delays cardiac repolarization, the aim of this trial was to evaluate the effects of a supratherapeutic dose of doravirine on the heart-rate corrected QT (QTc) interval in healthy adults. ⋯ A single oral supratherapeutic dose of doravirine 1200 mg does not cause clinically meaningful QTc interval prolongation in healthy adults.
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Review Meta Analysis
Interventions for Refractory Trigeminal Neuralgia: A Bayesian Mixed Treatment Comparison Network Meta-Analysis of Randomized Controlled Clinical Trials.
Patients with trigeminal neuralgia (TN) are often refractory to recommended first-line agents. Due to the absence of a systematic review, we undertook a network meta-analysis to assess various interventions that can be used to manage refractory TN. ⋯ We found that drug-related interventions that include sumatriptan, intranasal lidocaine, intravenous lidocaine, and botulinum toxin and combined continuous and pulsed radiofrequency thermocoagulation had significant effects in reducing pain in patients with refractory TN. However, the quality of evidence was graded as very low for all except botulinum toxin.
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Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of spinal motor neurons and poses significant adverse outcome in affected population. Survival motor neuron 1 (SMN1) protein encoded by SMN1 gene located on 5q13 is critical for survival and functioning of motor neurons. Almost identical gene SMN2, present on the same chromosome, produces a small truncated protein (SMN2) because of skipping of exon 7 from translation due to translation silent C6U substitution in exon 7 of SMN2 pre-mRNA transcript. ⋯ Major evidence of its efficacy came from a sham controlled phase 3 clinical study ENDEAR. The study was stopped early based on significantly favorable results in interim analysis and all the patients were transitioned to receive nusinersen in an ongoing open-label, phase 3 study, SHINE, which will evaluate the long-term efficacy, safety and tolerability of the drug. Nusinersen is globally the first drug approved (by the US FDA) for treatment of SMA in children and adults.
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Multicenter Study Observational Study
Effect of N-Acetylcysteine on Mortality and Liver Transplantation Rate in Non-Acetaminophen-Induced Acute Liver Failure: A Multicenter Study.
Previous studies and systematic reviews have not provided conclusive evidence on the effect of N-acetylcysteine (NAC) in non-acetaminophen-induced acute liver failure (NAI-ALF). We aimed to study the value of intravenous NAC in reducing liver transplantation and mortality in NAI-ALF. ⋯ When administered on admission, intravenous NAC caused a reduction in NAI-ALF mortality and need for transplantation. NAC decreased encephalopathy, hospital stay, ICU admission, and failure of other organs.