A 2022 review explored the dosing and schedule optimization of immune checkpoint-targeted antibodies, particularly anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) and anti-programmed cell death protein/ligand 1 (anti-PD-1/PD-L1) monoclonal antibodies, which have become pivotal in cancer immunotherapy. These therapeutic antibodies, including ipilimumab, nivolumab, pembrolizumab, atezolizumab, and others, were developed with dosing regimens largely guided by conventional models from chemotherapy, emphasizing fixed intervals or weight-based calculations. Development trials identified no dose-limiting toxicities for most PD-1/PD-L1 inhibitors, allowing fixed dosing options to evolve from weight-based regimens, despite notable economic and clinical implications. Fixed-dose regimens, such as pembrolizumab at 200 mg every three weeks or nivolumab at 480 mg every four weeks, were standardized based on average patient weights during trials, often leading to overexposure in low...

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From a 2021 review, the conventional use of high-dose corticosteroids for diffuse alveolar hemorrhage (DAH), often initiated with intravenous methylprednisolone pulses (500 mg to 2 g/day) for 3-5 days, was being re-evaluated. While this regimen aims to suppress the acute inflammatory lung injury, its benefit, particularly in critically ill patients, remains undefined, and associated mortality remains high. Emerging evidence questions the necessity of such high doses, as one study found that patients treated with lower-dose methylprednisolone (<250 mg/day) had significantly lower ICU mortality compared to those on medium or high doses, without a difference in overall mortality. Furthermore, research in related conditions like ANCA-associated vasculitis shows that reduced-dose glucocorticoids are equally effective for mortality and reduce serious infections, challenging the validity of high-dose corticosteroid protocols for DAH. [1, 2] In a paragraph within a 2021 review of acute a...

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A 2017 Cochrane review update analyzed whether inhaled corticosteroids, which theoretically offer localized lung benefits with fewer systemic side effects, are superior to systemic corticosteroids for preventing death or bronchopulmonary dysplasia (BPD) in ventilated, very low birth weight preterm infants. Based on two randomized controlled trials involving 294 infants, the analysis found no statistically significant difference between inhaled and systemic steroids for the primary outcomes of death or BPD at 36 weeks' postmenstrual age. However, key secondary outcomes revealed significant trade-offs: infants receiving inhaled steroids had a significantly longer duration of both mechanical ventilation and supplemental oxygen. On the other hand, they experienced a substantially lower incidence of hyperglycaemia but a higher rate of patent ductus arteriosus. A small long-term follow-up suggested a potential benefit of inhaled steroids in reducing later asthma diagnosis. The authors con...

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A 2020 systematic review evaluated intravaginal diazepam for chronic pelvic pain and sexual dysfunction associated with high-tone pelvic floor dysfunction. A total of five investigations met inclusion criteria (two observational studies and three small randomized controlled trials [RCTs]). The observational studies reported subjective improvements in sexual function in most patients, but no significant changes in Female Sexual Function Index (FSFI) or Visual Analog Scale (VAS) scores. The RCTs were largely negative, with one showing benefit only when diazepam was combined with transcutaneous electrical nerve stimulation. Additionally, limited pharmacokinetic data suggested systemic absorption within therapeutic ranges. Of note, this review did not specifically discuss the use of commercial oral diazepam tablets for intravaginal administration in pelvic floor dysfunction. However, the authors referenced one study where patients were offered either compounded diazepam cream or supposi...

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A 2023 systematic review and meta-analysis published in Annals of Emergency Medicine synthesized data from five randomized controlled trials (RCTs) encompassing 627 adult patients presenting to emergency departments (EDs) with acute pain. The review evaluated the comparative effectiveness and safety of low-dose (10-20 mg) versus high-dose (≥30 mg) parenteral (both intravenous and intramuscular) ketorolac; pain etiologies ranged from renal colic and musculoskeletal pain to abdominal and headache-related discomfort. Results from pooled analyses showed that parenteral ketorolac at doses of 15-20 mg likely produces no clinically meaningful difference in analgesia compared to doses ≥30 mg (mean difference -0.05 mm on a 100 mm visual analog scale [VAS], 95% CI -4.91 to +5.01; moderate certainty). Similarly, 10 mg dosing showed no significant effect on pain scores versus higher doses (mean difference -1.58 mm, 95% CI -8.86 to +5.71; low certainty). Low-dose ketorolac may be associated with...

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