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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A 2024 multicenter, randomized, open-label clinical trial, conducted across 22 intensive care units (ICUs) in Brazil, evaluated whether the addition of dapagliflozin to standard care improves clinical outcomes in critically ill patients with acute organ dysfunction. The trial enrolled 507 participants, aged 18 years or older, who had unplanned ICU admissions and presented with at least one organ dysfunction (e.g., respiratory failure, cardiovascular instability, or acute kidney injury). Participants were randomized 1:1 to receive either 10 mg of dapagliflozin orally or standard ICU care alone for up to 14 days or until ICU discharge. For patients with a contraindication to oral medication, dapagliflozin was administered enterally via oroenteral, orogastric, gastrostomy, or jejunostomy tube, following maceration and dilution in water. The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy (KRT), and ICU length of stay, analyze...

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There are multiple theories as to how statin therapy may increase the risk of diabetes, but a consensus has not been met. In vitro studies have found that diabetogenic statins can reduce insulin sensitivity and insulin secretion through inhibition of HMGCoAR (the main target of statin therapy) or impairing beta-cell function. Laasko et al. have noted that the majority of studies implicate simvastatin, atorvastatin, and rosuvastatin as the most diabetogenic statins in population-based studies, clinical studies, and in vitro experiments. A 2019 review concluded diabetic risk appears to be a classwide effect, with pravastatin and pitavastatin potentially having less impact on risk. Mechanistically, pitavastatin does not appear to impair adipocyte maturation at clinical doses, which may lead to improved leptin and adiponectin secretion. However, these studies and experiments are performed in vastly different scenarios, which makes it difficult to draw universal conclusions from the resu...

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A 2024 review provides an overview on current treatments for carbapenem-resistant A. baumannii (CRAB). Ampicillin-sulbactam is a unique β-lactam/β-lactamase inhibitor where the sulbactam component itself has direct, intrinsic antibacterial activity against Acinetobacter baumannii by binding to its penicillin-binding proteins. For CRAB infections, which are typically highly resistant, high-dose ampicillin-sulbactam (with daily sulbactam doses of 6 g to 9 g) is a valuable therapeutic strategy. This approach is pharmacologically rational, as sulbactam exhibits time-dependent activity, and high-dose, extended-infusion regimens are designed to maximize the time that drug concentrations remain above the pathogen's elevated minimum inhibitory concentration (MIC). Clinical evidence, primarily from smaller randomized trials and observational studies, shows that high-dose ampicillin-sulbactam-based regimens have clinical success and mortality rates comparable to, and sometimes better than, co...

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