Efficacy of a 3-day pretravel schedule of tafenoquine for malaria chemoprophylaxis: a network meta-analysis.

BACKGROUND: Chemoprophylaxis with weekly doses of tafenoquine (200 mg/day for 3 days before departure [loading dose], 200 mg/week during travel and 1-week post-travel [maintenance doses]) is effective in preventing malaria. Effectiveness of malaria chemoprophylaxis drugs in travellers is often compromised by poor compliance. Shorter schedules that can be completed before travel, allowing 'drug-free holidays', could increase compliance and thus reduce travel-related malaria. In this meta-analysis, we examined if a loading dose of tafenoquine alone is effective in preventing malaria in short-term travellers. METHODS: Four databases were searched in November 2020 for randomized controlled trials (RCTs) that assessed efficacy and/or safety of tafenoquine for chemoprophylaxis. Network meta-analysis using the generalized pair-wise modelling framework was utilized to estimate the odds ratio (OR) of malaria infection in long-term (>28 days) and short-term (≤28 days) travellers, as well as adverse events (AEs) associated with receiving loading dose of tafenoquine alone, loading dose of tafenoquine followed by maintenance doses, loading dose of mefloquine followed by maintenance doses, or placebo. RESULTS: Nine RCTs (1714 participants) were included. In long-term travellers, compared to mefloquine, tafenoquine with maintenance doses (OR = 1.05; 95% confidence interval [CI]: 0.44-2.46) was equally effective in preventing malaria, while there was an increased risk of infection with the loading dose of tafenoquine alone (OR = 2.89; 95% CI: 0.78-10.68) and placebo (OR = 62.91; 95% CI: 8.53-463.88). In short-term travellers, loading dose of tafenoquine alone (OR = 0.98; 95% CI: 0.04-22.42) and tafenoquine with maintenance doses (OR = 1.00; 95% CI: 0.06-16.10) were as effective as mefloquine. The risk of AEs with tafenoquine with maintenance doses (OR = 1.03; 95% CI: 0.67-1.60) was similar to mefloquine, while loading dose of tafenoquine alone (OR = 0.58; 95% CI: 0.20-1.66) was associated with lower risk of AEs, although the difference was not statistically significant. CONCLUSIONS: For short-term travellers, loading dose of tafenoquine alone was equally effective, had possibly lower rate of AEs, and likely better compliance than standard tafenoquine or mefloquine chemoprophylaxis schedules with maintenance doses. Studies are needed to confirm if short-term travellers remain free of infection after long-term follow-up. REGISTRATION: The meta-analysis was registered in PROSPERO (CRD42021223756). HIGHLIGHT: Tafenoquine is the latest approved drug for malaria chemoprophylaxis. A loading dose of tafenoquine (200 mg/day for 3 days before departure) is as effective in preventing malaria in short-term (≤28 days) travellers as chemoprophylaxis schedules of tafenoquine or mefloquine with maintenance doses, allowing travellers to have a 'drug-free holiday'.

Opioids combined with antidepressants or antiepileptic drugs for cancer pain: Systematic review and meta-analysis.

BACKGROUND: Combining antidepressant or antiepileptic drugs with opioids has resulted in increased pain relief when used for neuropathic pain in non-cancer conditions. However, evidence to support their effectiveness in cancer pain is lacking. AIM: To determine if there is additional benefit when opioids are combined with antidepressant or antiepileptic drugs for cancer pain. DESIGN: Systematic review and meta-analysis. Randomised control trials comparing opioid analgesia in combination with antidepressant or antiepileptic drugs versus opioid monotherapy were sought. Data on pain and adverse events were extracted. Data were pooled using DerSimonian-Laird random-effects meta-analyses, and heterogeneity was assessed. RESULTS: Seven randomised controlled trials that randomised 605 patients were included in the review. Patients' pain was described as neuropathic cancer pain, cancer bone pain and non-specific cancer pain. Four randomised controlled trials were included in the meta-analysis in which opioid in combination with either gabapentin or pregabalin was compared with opioid monotherapy. The pooled standardised mean difference was 0.16 (95% confidence interval, -0.19, 0.51) showing no significant difference in pain relief between the groups. Adverse events were more frequent in the combination arms. Data on amitriptyline, fluvoxamine and phenytoin were inconclusive. CONCLUSION: Combining opioid analgesia with gabapentinoids did not significantly improve pain relief in patients with tumour-related cancer pain compared with opioid monotherapy. Due to the heterogeneity of patient samples, benefit in patients with definite neuropathic cancer pain cannot be excluded. Clinicians should balance the small likelihood of benefit in patients with tumour-related cancer pain against the increased risk of adverse effects of combination therapy.

Investigating Methodological Differences in the Assessment of Dendritic Morphology of Basolateral Amygdala Principal Neurons-A Comparison of Golgi-Cox and Neurobiotin Electroporation Techniques.

Quantitative assessments of neuronal subtypes in numerous brain regions show large variations in dendritic arbor size. A critical experimental factor is the method used to visualize neurons. We chose to investigate quantitative differences in basolateral amygdala (BLA) principal neuron morphology using two of the most common visualization methods: Golgi-Cox staining and neurobiotin (NB) filling. We show in 8-week-old Wistar rats that NB-filling reveals significantly larger dendritic arbors and different spine densities, compared to Golgi-Cox-stained BLA neurons. Our results demonstrate important differences and provide methodological insights into quantitative disparities of BLA principal neuron morphology reported in the literature.

Differences in outcome between Maori and Caucasian patients undergoing total joint arthroplasty for osteoarthritis.

PURPOSE: To compare differences in outcome between Maori and Caucasian patients undergoing total joint arthroplasty for osteoarthritis. METHODS: 45 men and 45 women aged 43 to 87 years who underwent total hip (n=54) or total knee (n=36) arthroplasties by a single surgeon and were followed up for at least one year were prospectively studied. Patients were classified according to American Society of Anesthesiologists (ASA) score. Preoperative comorbidity, length of hospital stay, postoperative complications, and pre- and post-operative outcomes in the 2 groups were compared. RESULTS: Maori patients were more likely than Caucasian patients to be obese (body mass index of >30 kg/m square) [37% vs. 15%], diabetic (15% vs. 5%), and smokers (32% vs. 13%). Postoperative complication rates and the lengths of hospital stay in the 2 groups were not significantly different. The ASA score correlated positively with the length of hospital stay; higher ASA scores predicted more prolonged recovery. CONCLUSION: Maori patients were more likely than Caucasian patients to have preoperative comorbidities, but their postoperative length of hospital stay and complication rates were not significantly different.