Efficacy and Safety of Nifurtimox in Pediatric Patients with Chagas Disease: Results at 4-Year Follow-Up in a Prospective, Historically Controlled Study (CHICO SECURE).

Nifurtimox is recommended for the treatment of Chagas disease; however, long-term follow-up data are scarce. This prolonged follow-up phase of the prospective, historically controlled, CHICO clinical trial evaluated seronegative conversion in pediatric patients aged <18 years with Chagas disease who were followed for 4 years after nifurtimox treatment. Patients were randomly assigned 2:1 to nifurtimox 60-day or 30-day regimens comprising 10 to 20 mg/kg/day for patients aged <12 years and body weight <40 kg, and 8 to 10 mg/kg/day for those aged ≥12 years and body weight ≥40 kg. Anti-Trypanosoma cruzi antibodies decreased during the study period, achieving seronegative conversion in 16 (8.12%) and 8 (8.16%) patients in the 60-day and 30-day nifurtimox regimens, respectively, with corresponding incidence rates per 100 patients/year of seronegative conversion of 2.12 (95% confidence interval [CI]: 1.21 to 3.45) and 2.11 (95% CI: 0.91 to 4.16). Superiority of the 60-day nifurtimox regimen was confirmed by the lower limit of the 95% CI being higher than that (0%) in a historical placebo control group. Children aged <2 years at baseline were more likely to reach seronegative conversion during the 4-year follow-up than older children. At any annual follow-up visit, >90% of evaluable patients had persistently negative quantitative PCR results for T. cruzi DNA. No adverse events potentially related to treatment or caused by protocol-required procedures were documented for either treatment regimen. This study confirms the effectiveness and safety of a pediatric formulation of nifurtimox administered in an age- and weight-adjusted regimen for 60 days to treat children with Chagas disease.

Understanding Vulnerability to Late-Life Suicide.

PURPOSE OF REVIEW: We review recent evidence on suicide among older adults, examine risk factors contributing to vulnerability to late-life suicide, and summarize possible interventions. RECENT FINDINGS: We found a steadily increasing rate of late-life suicide in the USA in the past decade. Evidence supporting the integration of depression care managers into primary care for risk reduction is among the strongest to date. Pharmacologic and neuromodulation studies should be considered in geriatric depression complicated by suicidality. Broad societal campaigns about suicide education, as well as active outreach to psychiatric patients after discharge or a suicidal crisis, prevent suicidal behavior. Growing research supports an integrative multidisciplinary approach. Suicide is a complex and multifaceted behavior with numerous casual points for intervention. Access to deadly means, presence of depression, disease, disability, and social disconnection are factors that increase vulnerability. Quality geriatric care, regular screening in primary and emergency care settings, and a multidisciplinary approach are necessary to mitigate risk factors. The COVID-19 pandemic amplifies need for a more aggressive approach.

Comparison of Liposomal Bupivacaine and Conventional Local Anesthetic Agents in Regional Anesthesia: A Systematic Review.

BACKGROUND: Pain is one of the most common adverse events after surgery. Regional anesthesia techniques are effective for pain control but have limited duration of action. Liposomal bupivacaine is a long-acting formulation of bupivacaine. We conduct this systematic review to assess whether liposomal bupivacaine may prolong the analgesic duration of regional anesthesia compared to conventional local anesthetic agents. METHODS: We systematically searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE (Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Google Scholar, Web of Science citation index, US clinical trials register, and recent conference abstracts for relevant studies. RESULTS: We identified 13 randomized controlled trials that compared the use of liposomal bupivacaine to conventional local anesthetics in regional anesthesia. There were 5 studies on transversus abdominis plane (TAP) block, 3 of which reported longer duration of analgesia with liposomal bupivacaine. One study reported comparable analgesia with liposomal bupivacaine TAP block compared to TAP block catheter. There were 3 studies on brachial plexus block, 2 of which reported that liposomal bupivacaine may provide longer analgesia. Studies on other techniques did not report significantly longer analgesia with liposomal bupivacaine. CONCLUSIONS: Currently, there is limited evidence suggesting that liposomal bupivacaine provides longer analgesia than conventional local anesthetics when used in regional anesthesia. The analyses of multiple studies on liposomal bupivacaine for TAP blocks and brachial plexus blocks have yielded conflicting results. As a result, no definitive conclusions can be drawn about its efficacy compared to plain bupivacaine.