Clinical Pharmacology : Advances and Applications最新文献

Introduction: Malaria remains a persistent challenge in global health, disproportionately affecting populations in endemic regions (eg, sub-Saharan Africa). Despite decades of international collaborative efforts, malaria continues to claim hundreds of thousands of lives each year, with young children and pregnant women enduring the heaviest burden. This concise review aimed to provide an up-to-date assessment of malaria vaccines progress, challenges, and future directions.

Methods: A PubMed/MEDLINE search (2015-2024) was conducted to identify studies on malaria vaccine development, implementation barriers, efficacy, and vaccination hesitancy. Clinical trials, reviews, and global health reports were included based on relevance to the review aims. No strict inclusion criteria were applied, and selection was guided by key review themes and policy relevance.

Results: The introduction of pre-erythrocytic malaria vaccines (RTS,S/AS01 and R21/Matrix-M), represents an important milestone in malaria control efforts with promising results from the erythrocytic vaccine RH5.1/Matrix-M in recent clinical trials. However, the approval of these vaccines is accompanied by significant challenges such as the limited efficacy, the complexity of multi-dose regimens, and numerous barriers to widespread implementation in resource-limited settings. The review identified the complex challenges to broad malaria vaccination coverage, including logistical barriers, healthcare infrastructure effect, financial limitations, malaria vaccine hesitancy, among other obstacles in malaria-endemic regions. Promising developments in malaria vaccination, such as next-generation candidates (eg, mRNA-based vaccines), hold the potential to offer improved efficacy, longer-lasting protection, and greater scalability. There is a critical need to integrate malaria vaccination efforts with established malaria control interventions (eg, insecticide-treated bed nets, vector control strategies, and anti-malarial drugs).

Conclusion: Achieving sustained control of malaria morbidity and mortality will require strong global collaboration, sufficient funding, and continuous efforts to address inequities in access and delivery of malaria control measures including the malaria vaccines.

Crotalidae polyvalent immune Fab (CroFab) is an antivenin that is FDA approved and commonly used to treat envenomations caused by North American pit vipers. Although CroFab has been widely used since the early 2000s, hypersensitivity reactions like type I, type IV, and angioedema have been reported in the literature. We present a case of CroFab induced hypersensitivity reaction in a 41-year-old male shortly after starting CroFab infusion. Furthermore, this patient developed anaphylaxis symptoms including: difficulty breathing, oropharyngeal edema, dysphagia, wheezing, and chest tightness. This was resolved upon stopping CroFab infusion and administering epinephrine, methylprednisolone, diphenhydramine, and famotidine. The reaction occurred again when CroFab was re-introduced despite infusing it at a much slower rate. Interestingly, this patient successfully tolerated crotalidae immune F(ab')2 (equine) antivenom (ANAVIP) upon switching him from CroFab. Hypersensitivity reactions to CroFab can be life-threatening and warrant immediate attention and treatment in a multidisciplinary setting.

Introduction: Curcumin is an extract from herbal plants that has been implicated in the treatment of any disease, including oral disease. There are various types of curcumin formulation as the option of the therapy. The aim of this review is to describe the curcumin mechanism in reducing the severity, pain score, and oral lesion size as the therapeutic effects.

Methods: This systematic review used the Preferred Reporting Items for Systematic Review and Meta Analysis (PRISMA) guidelines. Databases used for articles include PubMed, Science Direct, and Scopus with inclusion criteria published from 2014 to 2024, full text, in English, and randomized controlled trial (RCT).

Results: The present study included 21 RCTs with a total of 1244 individuals. In this study, curcumin was most commonly used for oral submucous fibrosis, with 9 studies demonstrating that curcumin has anti-inflammatory properties and inhibits collagenase. All studies demonstrate that curcumin produces significant results in the management of oral disease. The remain studies showed curcumin has antioxidant, inhibit collagenase, antifungal, and wound healing properties for oral leukoplakia, recurrent aphthous stomatitis (RAS), oral lichen planus (OLP), and denture stomatitis.

Conclusion: Curcumin has anti inflammatory, antioxidant, inhibit collagenase, antifungal, and wound healing properties for reducing the severity of lesion, pain score and oral lesion size as the therapeutic effects in the patients with oral disease including OSMF, mucositis, leukoplakia, RAS, OLP, and denture stomatitis.

Various repurposing drugs have been tested for their efficacy on coronavirus disease 2019 (COVID-19), including antimalarial drugs. During the pandemic, Chloroquine (CQ) and Hydroxychloroquine (HCQ) demonstrated good potential against COVID-19, but further studies showed both drugs had side effects that were more dangerous than the efficacy. This made World Health Organization (WHO) ban the usage for COVID-19 patients. In this context, there is a need to explore other antimalarial drugs as potential therapies for COVID-19. This study provides a descriptive synthesis of clinical trials evaluating antimalarial drugs for COVID-19 treatment conducted after the withdrawal of CQ and HCQ. The method was a literature study using the keywords "antimalarial", "COVID-19", "SARS-CoV-2", "clinical trial", and "randomized controlled trial" on the MEDLINE, Scopus, and Cochrane databases. Inclusion criteria were published clinical trials with randomized controlled trials (RCTs) on the efficacy and safety of single antimalarial drugs for COVID-19, published in English and excluding combination therapies. The results showed 3 antimalarial drugs, namely Quinine Sulfate (QS), Atovaquone (AQ), and Artemisinin-Piperaquine (AP), had gone through clinical trial to assess efficacy and safety against COVID-19 patients. Out of the 3 drugs, only AP showed significant results in the primary outcome, which was the time required to reach undetectable levels of SARS-CoV-2. Furthermore, the intervention group took 10.6 days, and the control group took 19.3 days (p=0.001). Based on this review, AP showed significant potential as a therapy in the fight against COVID-19.

Background: Heparin and its derivates, including unfractionated heparin (UFH) and low molecular weight heparin (LMWH), are among the most commonly used anticoagulants. Nonetheless, their use has been associated with hyperkalemia.

Objective: To determine and compare the incidence, magnitude, and potential risk factors of hyperkalemia in patients receiving UFH versus LMWH in a real-world clinical setting.

Methods: A retrospective observational study was conducted involving all adult hospitalized patients who received UFH, dalteparin or enoxaparin. Electronic medical records were reviewed over a 12-month period, collecting data on demographic, laboratory, comorbidity, and medication-related variables. Data were analyzed using multivariate logistic regression.

Results: A total of 929 patients met the eligibility criteria, with a mean age of over 40 years across all groups. Of these, 56.3%, 17.2%, and 15.7% experienced hyperkalemia with UFH, dalteparin and enoxaparin, respectively. The incidence of hyperkalemia was significantly higher with UFH compared to enoxaparin and dalteparin (p<0.001). Diabetes mellitus was associated with a higher incidence of hyperkalemia (OR 1.79, 95% CI 1.241-2.581, p=0.002), as was the concomitant use of co-trimoxazole (OR 2.244, 95% CI 1.137-4.426, p=0.02). Whilst chronic kidney disease and the use of two or more hyperkalemia-inducing agents were not statistically significant, they were retained in the model as they were associated with more than a 10% increase in the odds of hyperkalemia.

Conclusion: Heparin (UFH, LMWH) administration was associated with a risk of hyperkalemia particularly in patients with diabetes mellitus and those concurrently receiving co-trimoxazole.

Dexmedetomidine is a selective and potent α₂-adrenoceptor agonist used for sedation, analgesia, and anxiolysis, with minimal respiratory depression; therefore, it is widely used in clinical practice. Transient hypertension has been reported to be an indication for the use of dexmedetomidine. The authors report three female patients who experienced hypertensive crisis when used atropine to treat bradycardia caused by dexmedetomidine. The transient hypertension is a relatively common side effect of dexmedetomidine, hypertensive crisis seen with coadministration of atropine is much less frequently reported. This is the first report to describe the use of atropine to treat bradycardia induced by dexmedetomidine, which may cause severe hypertension in female patients. They discuss the reason for and treatment of hypertension caused by administration of atropine and dexmedetomidine together and review the relevant literature.

Medication errors have the potential to cause serious toxicity and hospitalization. This case report describes a 25-year woman who suffered serious side effects and was ‎hospitalized after receiving intravenous ipratropium bromide/salbutamol. This was due to a medication error in its preparation and administration. The caregiver diluted an intravenous antibiotic with the incorrect diluent (nebulizer solution), which led to serious toxicity, including acute urine retention and sinus tachycardia, and then resulted in patient hospitalization. A literature review of case reports was conducted to compare and identify the pattern of ipratropium/salbutamol-induced acute urinary retention. The present report underscores the importance of clinical awareness about medication-induced acute urine retention. Furthermore, it is crucial that physicians inform and educate the patients and their carers about double-checking doses and labelling before administering medication, particularly for intravenous drugs.

Allopurinol is a commonly used medication that lowers uric acid production which is essential for gout treatment and prevention. Although many patients tolerate allopurinol therapy without severe complications; Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are life-threatening delayed hypersensitivity reactions that have been reported especially among Asian and African American patients. We describe a case of allopurinol-induced SJS in a 95-year-old Asian female. The patient started allopurinol 13 days prior to presenting to the emergency room (ER). On day 10 of therapy, the patient developed a diffuse erythematous desquamating rash which prompted her to visit the ER after 3 days from the rash onset. This case report describes a rare fatal hypersensitivity reaction that requires rapid identification and treatment in a multi-disciplinary setting.

Background: Emergence of antimalarial drugs and insecticides resistance alarms scientists to develop a safe and effective malaria vaccine. A pre-erythrocytic malaria vaccine called RTS,S has made great strides.

Aim: The review was aimed to assess the safety of the candidate malaria vaccine RTS,S with AS01 and AS02 adjuvants using data from Phase I-III randomized controlled clinical trials (RCTs).

Methods: This systematic review was conducted based on PRISMA 2020. Regardless of time of publication year, all articles related with safety of RTS,S, RCTs published in the English language were included in the study. The last search of databases, and registry was conducted on 30 May, 2022. Pubmed, Google Scholar, Cochrane Library, Wiley Online Library, and Clinical trials.gov were thoroughly searched for accessible RCTs on the safety of RTS,S malaria vaccine. The studies were screened in three steps: duplicate removal, title and abstract screening, and full-text review. The included studies' bias risk was assessed using the Cochrane risk of bias tool for RCTs. This systematic review is registered at Prospero (registration number: CRD42021285888). The qualitative descriptive findings from the included published studies were reported stratified by clinical trial phases.

Findings: A total of thirty-five eligible safety studies were identified. Injection site pain and swelling, febrile convulsion, fever, headache, meningitis, fatigue, gastroenteritis, myalgia, pneumonia, reactogenicity, and anemia were the most commonly reported adverse events. Despite few clinical trials reported serious adverse events, none of them were related to vaccination.

Conclusion: Most of the adverse events observed from RTS,S/AS01 and RTS,S/AS02 malaria vaccines were reported in the control group and shared by other vaccines. Hence, the authors concluded that both RTS,S/AS01 and RTS,S/AS02 malaria vaccines are safe.