Evaluating the use of paracetamol to prevent fasting headache during the first week of Ramadan: A randomized, open-label, clinical trial.

BACKGROUND: Fasting headaches frequently occur during the first few days of Ramadan, and treatment is challenging because of fasting. OBJECTIVE: This study aimed to evaluate the effect of extended-release paracetamol on preventing fasting headaches. METHODS: A randomized, open-label clinical trial investigated the efficacy of extended-release paracetamol at a daily dose of 1330 mg in preventing fasting headache. Adults aged 18 years and older were recruited through the Clinical Trial Unit at the King Saud University Medical City. The eligible participants in the study fasted 13.5 h daily during the first week of Ramadan. Participants in the treatment and control arms were followed up to investigate the occurrence, severity, and timing of headache symptoms via self-reporting using a standardized headache diary scale with a daily online link or phone call. The primary outcome was the frequency of headache episodes while fasting during the first week of Ramadan. RESULTS: A total of 238 participants were enrolled and randomized. Of these, 173 followed the protocol (80 treated, 93 control) for at least the first day and were included in the analysis. Most participants were young and healthy, with a mean age of 32.2 ± 10.2 years. More men were included in the study (102/173; 59.0%), a small proportion of participants were smokers (31/173; 17.9%), and almost all participants reported being coffee drinkers (165/173; 95.4%); nonetheless, these characteristics were evenly distributed between the two groups in the study. The overall incidence of headache episodes was 33.0% (57/173) on day 1 and decreased to 11.3% (18/159) on day 7. On average over the 7 days, no significant effect was observed for the treatment on the incidence of headache, as the findings from the generalized estimating equation model indicated (ß = -0.398, p = 0.084; odds ratio = 0.67, 95% confidence interval [CI] 0.42-1.06). Moreover, there was initially no significant difference in the incidence of headache episodes between the treatment and control groups. However, the treatment group had significantly fewer headache episodes during fasting than the control group on day 3 (4/72 [5.6%] vs. 15/91 [16.5%], p = 0.031; relative risk [RR] = 0.34, 95% CI 0.12-0.97) and day 6 (5/69 [7.2%] vs. 20/90 [22.2%], p = 0.010; RR = 0.33, 95% CI 0.13-0.82). No adverse effects were observed during the study period. CONCLUSION: No significant differences were observed in the occurrence of fasting headaches between the two groups on most days during the study period. Additional studies are required to address fasting headaches during the first week of Ramadan.

Co-Delivery of Dragon's Blood and Alkanna tinctoria Extracts Using Electrospun Nanofibers: In Vitro and In Vivo Wound Healing Evaluation in Diabetic Rat Model.

The increasing prevalence of diabetic wounds presents a significant challenge due to the difficulty of natural healing and various obstacles. Dragon's blood (DB) and Alkanna tinctoria (AT) are well recognized for their potent healing abilities, which include potent antibacterial and anti-inflammatory activities. In this study, electrospun nanofibers (NFs) based on polyvinyl pyrrolidone (PVP) were co-loaded with both DB and AT, aiming to magnify their efficacy as wound-dressing applications for diabetic wound healing. The evaluation of these NFs as wound dressings was conducted using a streptozotocin-induced diabetic rat model. Electrospun NFs were prepared using the electrospinning of the PVP polymer, resulting in nanofibers with consistent, smooth surfaces. The loading capacity (LC) of AT and DB into NFs was 64.1 and 70.4 µg/mg, respectively, while in the co-loaded NFs, LC was 49.6 for AT and 57.2 µg/mg for DB. In addition, X-ray diffraction (XRD) revealed that DB and AT were amorphously dispersed within the NFs. The loaded NFs showed a dissolution time of 30 s in PBS (pH 7.4), which facilitated the release of AT and DB (25-38% after 10 min), followed by a complete release achieved after 180 min. The antibacterial evaluation demonstrated that the DB-AT mixture had potent activity against Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). Along with that, the DB-AT NFs showed effective growth inhibition for both P. aeruginosa and S. aureus compared to the control NFs. Moreover, wound healing was evaluated in vivo in diabetic Wistar rats over 14 days. The results revealed that the DB-AT NFs improved wound healing within 14 days significantly compared to the other groups. These results highlight the potential application of the developed DB-AT NFs in wound healing management, particularly in diabetic wounds.

Are drug safety measures harmonized? A real-world evidence from three regulatory authorities.

Background: Risk minimization measures (RMMs) are interventions intended to mitigate or prevent the occurrence of adverse reactions associated with medications. Having consistent measures across regulatory bodies (i.e., the Saudi Food and Drug Authority (SFDA), the United States Food and Drug Administration (US FDA), and the European Medicines Agency (EMA)) benefits medication use and safety and ultimately the patient. Objectives: This study aimed to investigate whether there is variability in these published RMMs between the three regulatory bodies. Methods: A specific data collection form was created to extract information from the SFDA's RMM list, US FDA's Risk Evaluation and Mitigation Strategy (REMS) list, and EMA's Risk Management Plan (RMP) list, as of February 2022 all RMMs that were available on the websites were reviewed. Medications with the same trade name were matched across regulators, and unmatched medications were checked for approval status. For medication groups such as NSAIDs in the SFDA's RMM list, they were matched by searching for the groups individually in the regulatory websites. All risks and types of minimizing measures were compared. Results: A total of 317 medications were retrieved from the SFDA's RMM list. The majority of medication classes were immunosuppressants (n = 60), antihypertensive (n = 33), and oncology medication (n = 29). There were only 62 medications with REMS from the US FDA website, a total of 14 medications were approved by the SFDA, and only nine medications were matched with the SFDA's RMM list. Also, there were 828 medications with RMP from the EMA website, a total of 334 has RMM, 128 are approved by the SFDA, and 71 matched with the SFDA's RMM list. Furthermore, seven medications were matched between SFDA, US FDA and EMA. After content review, four medications had similar risks and measures across the regulators and three medications had different risks and measures across the regulators. For the medication groups, a total of 36 groups were in the SFDA's list, 18 groups were matched with the US FDA, and 14 were matched with the EMA. Conclusions: Our study showed substantial differences among the regulatory authorities regarding RMMs. Harmony in published risk measures can have a significant impact on medication safety.

Aspartames Alter Pharmacokinetics Parameters of Erlotinib and Gefitinib and Elevate Liver Enzymes in Wistar Rats.

Background: Erlotinib (ERL) and gefitinib (GEF) are extensively metabolized by CYP450 enzymes. Aspartame (ASP), an artificial sweetener, induces CYP2E1 and CYP3A2 enzymes in the brain and could increase liver enzymes. In this work, the influence of ASP on the pharmacokinetics (PK) of ERL and GEF in Wistar rats was evaluated. Methods: The PKs of ERL and GEF were evaluated after receiving 175 mg/kg or 1000 mg/kg of ASP for four weeks using UPLC-MS/MS. Levels of liver enzymes after four weeks of ASP consumption were also evaluated. Results: ASP 175 mg/kg was able to significantly alter levels of Cmax (36% increase for ERL, 38% decrease for GEF), AUC0-72 (205% increase for ERL, 41% increase for GEF), and AUC0-∞ (112% increase for ERL, 14% increase for GEF). Moreover, ASP 175 mg/kg decreased the apparent oral clearance ERL and GEF by 58% and 13%, respectively. ASP 1000 mg/kg increased Cmax of ERL by 159% and decreased GEF's Cmax by and 73%. Both AUC0-72 and AUC0-∞ were increased by ASP 1000 for ERL and decreased for GEF. CL/F decreased by 64% for ERL and increased by 38.8% for GEF. Moreover, data indicated that ASP significantly increased levels of liver enzymes within two weeks of administration. Conclusions: Although ASP 175 and 1000 mg/kg alter ERL and GEF PKs parameters, ASP 1000 mg/kg has the highest impact on most parameters. ASP 1000 mg/kg also can significantly increase activities of liver enzymes indicating the possibility of inducing liver injury. Therefore, it might be of clinical importance to avoid the administration of aspartame containing products while on ERL or GEF therapy.