Effect of standard dose paracetamol versus placebo as antipyretic therapy on liver injury in adult dengue infection: a multicentre randomised controlled trial.

BACKGROUND: Dengue is a common cause of acute liver failure in tropical countries. Paracetamol is the recommended antipyretic for dengue. Related observational studies in dengue have suggested that excessive paracetamol intake is related to hepatic injury. We aimed to evaluate whether standard dose paracetamol as an antipyretic in dengue infection caused transaminase elevation, and to evaluate the efficacy of paracetamol. METHODS: In this randomised, double-blind, placebo-controlled trial, adult participants (aged ≥18 years) with dengue, as confirmed by either positive NS1 antigen, positive dengue IgM antigen with thrombocytopenia, or positive PCR test, were enrolled at three Royal Thai Army hospitals in Thailand. Key exclusion criteria were baseline AST or ALT concentrations of more than 3 times the upper limit of normal, cirrhosis, indication of paracetamol other than dengue infection, concurrent diagnosis of other causes of fever, or pregnancy. Patients were randomly assigned (1:1), by a computer-generated block randomisation procedure (block size of six), to receive either paracetamol (500 mg) or placebo (500 mg) every 4 h when body temperature exceeded 38°C during hospitalisation. Participants and investigators were masked to treatment assignment. The primary outcome was the proportion of participants with transaminase elevation, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) concentrations of more than 3 times the upper limit of normal on recovery day, in the intention-to-treat population. Prespecified interim analyses for safety and efficacy were performed with group sequential stopping boundaries. This trial is registered with ClinicalTrials.gov, number NCT02833584. FINDINGS: Between Sept 1, 2016, and Dec 12, 2017, 125 participants were randomly assigned to receive either paracetamol (n=63) or placebo (n=62). 123 participants were included in the intention-to-treat population. The median daily dose of study medication was 1·5 g (IQR 0·8-2·0). The study was terminated early owing to a higher rate of transaminase elevation in the paracetamol group than in the placebo group (22% vs 10%; incidence rate ratio 3·77, 95% CI 1·36-10·46, p=0·011). The change of AST and ALT concentrations in the paracetamol group was higher than in the placebo group (mean difference 12·43 U/L per day, 7·16-17·71, p<0·0001 for AST; 7·40 U/L per day, 95% CI 3·68-11·13, p=0·0001 for ALT). Three participants in the paracetamol group had severe dengue: two had upper gastric haemorrhage and one had acute kidney injury. No patients died or had liver failure. INTERPRETATION: Use of standard dose paracetamol in dengue infection increased the incidence of transaminase elevation, and also overall transaminase concentrations in the absence of a counterbalancing reduced fever or pain score. FUNDING: Phramongkutklao College of Medicine.

Dural sinus thrombosis in melioidosis: the first case report.

Melioidosis which is infection with Burkholderia pseudomallei, is an important cause of sepsis in India, southeast Asia and northern Australia. Mortality is high and treatment is problematic. Neurological melioidosis is unusual but meningoencephalitis, encephalomyelitis and brain microabscess can occur Dural sinus thrombosis is not an uncommon cerebrovascular disorder with various etiologies. Hypercoagulable state, pregnancy, dehydration, certain blood dyscrasia and contraceptive pills are common causes however meningitis and local head & neck infections may lead to this condition. Dural sinus thrombosis complicating septicemic melioidosis has never been reported. The authors report a 42-year-old Thai man suffering from septicemic melioidosis with dural sinus thrombosis. He had high fever, headache, left hemiparesis, focal seizure and increased intracranial pressure. Diabetes and mild alcoholic cirrhosis were diagnosed in this admission. CT scan, MRI brain and MRV revealed superior saggital sinus thrombosis with complicating venous infarction over right posterior parietal lobe. Hemoculture demonstrated Burkholderia pseudomallei and CSF was acellular Investigations for causes of dural sinus thrombosis were all negative. This patient gradually improved after treatment with ceftazidime, antiepileptic drug and heparin without clinical recurrence. Neuromelioidosis is a rare syndrome that may present as brain abscess, encephalitis or meningoencephalitis. The authors report dural sinus thrombosis associated with septicemic melioidosis. The authors' hypothesis of venous thrombosis in the presented case is sepsis induced hypercoagulable state. Physicians should be aware of cerebral venous thrombosis in case of suspicious melioidosis with neurological involvement. Prompt treatment with intravenous heparin and antibiotic is potentially effective.

Dementia and depression in end stage renal disease: comparison between hemodialysis and continuous ambulatory peritoneal dialysis.

OBJECTIVES: To determine the prevalence, risk factors of dementia and depression in end stage renal disease (ESRD) who were treated with hemodialysis (HD) compared with those who had continuous ambulatory peritoneal dialysis (CAPD). MATERIAL AND METHOD: A cross-sectional study was conducted on 90 ESRD patients (60 HD and 30 CAPD groups). The authors reviewed the demographic data, investigation results. Thai Mental State Examination, DSM IV criteria and Thai Depression Inventory were interviewed to determine dementia and depression respectively. RESULTS: Both prevalence of dementia and depression in ESRD on continuous dialysis were 6.7%. In the HD group had 8.3% prevalence of dementia and 6.7% of depression, whereas there was 3.3% of dementia and 6.7% of depression in the CAPD group. The severity of depression in the present study was mild to moderate (6.7%) and no major depression was seen. The significant risk factors for dementia were age > or = 60 years (p=0.003), Education < 10 years (p=0.037) and female sex (p=0.036). The significant risk factor for depression was female sex (p=0.036). There was no significance different on prevalence of dementia and depression comparison between the HD and CAPD group. CONCLUSION: Prevalence of dementia and depression in the overall dialysis in ESRD was 6.7% (with 8.3%, 6.7% among the HD group and 3.3%, 6.7% among CAPD group). There was no significant difference on prevalence of dementia and depression comparison between the HD and CAPD group.

Comparison between aspirin combined with dipyridamole versus aspirin alone within 48 hours after ischemic stroke event for prevention of recurrent stroke and improvement of neurological function: a preliminary study.

OBJECTIVES: To determine efficacy and tolerability of aspirin plus dipyridamole (combination) versus aspirin alone in acute intervention treatment after acute ischemic stoke among Thai patients. MATERIAL AND METHOD: This pilot study enrolled ischemic stroke patients within 48 hours and randomized to aspirin 300 mg/d or combination (aspirin 300 mg/d+ standard release dipyridamole 75 mg thrice a day) and followed up for 6 months. Endpoints were recurrent ischemic stroke, transient ischemic attack and vascular death. Side effects were recorded. National Institutes of Health Stroke Scale was assessed at entry and at 6 months period for determining neurological functions. RESULTS: Of 38 patients, mean age was 64.3 years. Male and female were 52.6% and 47.4% respectively. There were 18 patients in the aspirin group and 20 patients in the combination group. No patient developed end point events or no significant adverse event in both groups. The combination group showed more improvement in neurological function than the aspirin group (p-value 0.009). CONCLUSION: This pilot study showed equal efficacy and tolerability of the combination group and aspirin alone in acute intervention treatment for prevention of recurrent stroke or vascular death within 6 months.