Background: Diabetes impacts negatively many aspects of global development including economic sustainability and human development. The burden of diabetes with its increasing prevalence causes a harsh financial decline hence, the quest for a permanent solution. Plant stem cell therapy has the potential to drastically change the narrative of scientific research from the perspective of being reactive to preventive and restorative. Objective: This study sought to determine the pharmacotherapeutic effect of the aqueous stem cell extract of Malus domestica (MD) in rats Method: Antidiabetic effect of the aqueous extract of MD (50,100, 200, and 400 mg/kg) was investigated in normoglycemic and oral glucose-induced hyperglycemic rats that were fasted overnight. Furthermore, acute oral toxicity studies were conducted using the limit dose test of the Up-and-Down Procedure according to OECD/OCDE test guidelines on acute toxicity. In addition, α-amylase and α-glucosidase enzyme inhibitory assays, phytochemical analysis, and antioxidant activity were assessed. Results: The phytochemical constituents exhibited flavonoids, phenols, phlobatannins, reducing sugars, carbohydrates, steroids, and cardiac glycosides. No mortality or signs of toxicity after oral administration with a single dose of 5 g/kg of the MD aqueous extract was recorded. Inhibition of α-amylase and α-glucosidase, positive antioxidant scavenging activity, and a significant (p < 0.0001) reduction in blood glucose level in the hyperglycemic-induced rats but not the normoglycemic were discovered. Pearson correlation showed an association between 50 and 100 mg/kg of MD and glibenclamide. Conclusion: There could be a strong correlation between MD as a potential antidiabetic drug due to the antioxidant properties it possesses.

Abstract Aim: we sought to estimate the association between hypoglycemic medications especially sodium-glucose co-transporter-2 inhibitors (SGLT2i) and osteomyelitis based on the FDA adverse event reporting system (FAERS). Methods: Publicly available FAERS data were analyzed using reporting odd ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. The developing trend of ROR were revealed by series of calculation based on accumulating dataset quarter by quarter. Results: Ketoacidosis, infections, peripheral ischemia, renal impairment, inflammation including osteomyelitis might more likely to occur among SGLT2i users, especially canagliflozin. Osteomyelitis and cellulitis are AEs unique to canagliflozin. Among 2,888 osteomyelitis-related reports referring to glucose lowering medications, 2,333 cases were associated with SGLT2i, mostly with canagliflozin counting 2,283 which generated an ROR value of 360.89 and a lower limit of information component (IC025) of 7.79. No BCPNN-positive signal could be generated for drugs other than insulin, canagliflozin or drug groups excluding canagliflozin. Reports referring to insulin could generate BCPNN-positive signals during the entire timespan from 2004 to 2021, while BCPNN-positive signal emerged since second quarter (Q2) of 2017, four years since the approval of SGLT2i in Q2 of 2013, for canagliflozin and drug groups containing canagliflozin. Conclusion: This data mining revealed that strong association between canagliflozin treatment and developing osteomyelitis which might be a precursor to lower extremity amputation. Further study with updated data is needed to better characterize the risk of osteomyelitis associated with SGLT2i.

Aims: Nusinersen is administered intrathecally for treating spinal muscular atrophy (SMA). Procedural sedation is common with intrathecal treatment in children. This retrospective study presents our experience with procedural sedation during the intrathecal treatment of pediatric patients with SMA I, II, and III. Methods: Data were collected the from the anesthesia charts and electronic medical records of 14 pediatric patients with SMA types I, II, and III who underwent procedural sedation for repeated intrathecal treatments for SMA. Intravenous induction was performed, and patients were oxygenated with a face mask or nasal cannula while spontaneous breathing continued. Results: Fourteen patients were included in the study: one SMA I, eight SMA II, and five SMA III. They underwent 88 intrathecal nusinersen injections totally. In the one SMA I patient, of eight months, the procedure was performed under local anesthesia. In all other patients, the treatments were performed under procedural sedation. Different combinations of midazolam, ketamine, propofol, fentanyl, and remifentanil were used. The mean doses of the agents used were 0.03 mg/kg, 0.97 mg/kg, 2.71 mg/kg, 0.84 mcg/kg and 0.5 mcg/kg respectively. There were no intraoperative or postoperative complications. Conclusion: We found the procedural sedation to be sufficient, effective, and safe in SMA II and III pediatric patients who underwent nusinersen treatment intrathecally, provided anesthetic agents are titrated.and administered carefully.

There is a strong scientific rationale to use nebulised unfractionated heparin (UFH) in COVID-19. This pilot study investigated whether nebulised UFH was safe and had any impact on mortality, length of hospitalisation and clinical progression, in the treatment of hospitalised patients with COVID-19. This parallel group, open label, randomised trial included adult patients with confirmed SARS-CoV-2 infection admitted hospital in Brazil. One hundred patients were planned to be randomised to either “standard of care” (SOC) or SOC plus nebulized UFH. The trial was stopped after randomisation of 75 patients due to falling COVID-19 hospitalisation rates. Significance tests were 1-sided test (10% significance level). The key analysis populations were intention to treat (ITT) and modified ITT (mITT) which excluded (from both arms) subjects admitted to ITU or who died within 24 hrs of randomisation. In the ITT population (n=75), mortality was numerically lower for nebulised UFH (6 out of 38 patients; 15.8%) versus SOC (10 out of 37 patients; 27.0%), but not statistically significant; odds ratio (OR) 0.51, p=0.24. In the mITT population, nebulised UFH reduced mortality (OR 0.2, p=0.035).

Smoking remains the leading cause of preventable death worldwide. Nicotine Replacement Therapies (NRTs) are the most commonly used smoking cessation medications. However, the scope of these treatments is limited: drop-out rates are high and their effectiveness is modest. We believe that nicotine tapering plays an important role in overall smoking cessation efficacy. However, each of the NRTs currently on the market have been approved on the basis of either a unique tapering strategy or none at all. Therefore, it is unknown whether improved efficacy and safety outcomes could have been achieved by using different approaches. Moreover, dosing regimens of marketed NRTs lack personalization. They are based on a “one-size-fits-all” approach, which is not optimal given that smokers represent a highly heterogeneous group. The emergence of digital health and Electronic Nicotine Delivery Systems (ENDS), which have demonstrated superior outcomes compared to NRTs in terms of smoking cessation rates, give way to the development of new innovative ways to gradually reduce nicotine in a personalized fashion, without the limitations of currently approved NRTs.

Abstract Dopamine agonists are a key tool in the therapeutic arsenal of endocrinologists worldwide. They exert their effects by binding to dopamine 2 (D2) receptors expressed by pituitary tumor cells, to modulate hormonal secretion and tumor size. They are the established first-line treatment for prolactinomas which express high levels of D2 receptors. Growing data supports their use as an adjuvant treatment option for other pituitary tumors including growth hormone, adrenocorticotrophic hormones, thyroid hormone secreting adenomas and non-functional pituitary tumors, all of which have been shown to express D2 receptors as well, albeit to varying extents. For those pituitary tumors inadequately treated by dopamine agonist alone, combined agonism of D2 and somatostatin receptors, represent a new frontier in clinical development. Here we review the development and role of dopamine agonist for the treatment of prolactinomas, the literature supporting their adjuvant use for the treatment of all other pituitary tumors, and recent progress in the development of the next generation of chimeric compounds that target D2 and other receptor subtypes highly expressed on pituitary tumor cells.

Introduction Orthostatic hypotension (OH) is associated with cardiovascular mortality and morbidity. Non-pharmacological and pharmacological therapies are employed in the management of OH. The aim of this systematic review and meta-analysis is to provide an up-to-date review of the efficacy parameters of pharmacological therapies. Methods Medline, Embase, Cochrane Library, and Scopus were searched (inception-July 2021), and published articles with randomized control trials, meeting inclusion and exclusion criteria were quality assessed (Risk of Bias 2 tool). Assessment for trends in patient-related outcome measures and postural blood pressure improvement was undertaken. Studies reporting postural systolic blood pressure (SBP) before and after intervention in comparison to placebo were included in a meta-analysis using inverse -variance in a random-effects model. Results 19 articles were included in the systematic review. The orthostatic symptoms questionnaire (OHQ) was the most common patient-related outcome measure utilized in trials. Six studies included in the meta-analysis demonstrated that pharmacological therapies (pyridostigmine, midodrine, atomoxetine, yohimbine) improved postural SBP compared to placebo, with a mean rise of 12.50 mmHg [95% CI: 6.01, 18.98; p value<0.001, I2 =97%]. Midodrine showed the highest impact on SBP, with a mean SBP of 16.11 mmHg [95% CI: 5.59, 26.63; p=0.003, I2 =99%]. Conclusions Pharmacological treatment can significantly increase postural SBP, however with significant heterogeneity related to trial designs. Further efforts to homogenize outcome measures, incorporating symptom improvement and reduction in the postural drop and testing for a prolonged duration of therapy would strengthen the evidence, and improve the translatability of findings in clinical settings.

The effects of polymorphisms of ABCB1 and ABCG2 on the dose-adjusted plasma trough concentrations and cerebrospinal fluid (CSF)-to-plasma ratios of ponatinib were evaluated. Blood (C4) and CSF (CSF4) concentrations at 4 h after administration were determined. The median (95% confidence interval (CI)) CSF4-to-C4 ratio of ponatinib in subjects homozygous for ABCB1 variants 1236T/T, 2677T/T+T/A, or 3435T/T were significantly higher than that in a group of subjects with other genotypes (P = 0.026, 0.012, and 0.015, respectively). The median (95% CI) CSF4-to-C4 ratio of ponatinib in four patients with the combination of ABCB1 variants 1236T/T-2677T/T+T/A-3435T/T was 2.62 (1.42 – 3.42)%; this ratio was significantly higher than that in subjects with other genotypes [1.08 (0.89 – 1.47)%; P = 0.006]. The brain distribution of ponatinib was affected by ABCB1 polymorphisms and therefore seems to be modulated by P-glycoprotein at the blood-brain and blood-CSF barriers.

Inappropriate medication use has become an important factor affecting the safety of rational medication. Most traditional medical anomaly detection systems are based on rules to regulate inappropriate medication use。 In this paper, we model the complex relationships among patients, diseases, and medicine based on medical big data to promote appropriate medication use. More specifically, we first construct the medication knowledge graph based on the historical prescription big data of tertiary hospitals and medical text data. Second, based on the medication knowledge graph, we employ a Gaussian Mixture Model (GMM) to represent patients in groups as physiological features. For diagnostic features, we employ the pre-training word vector BERT to enhance the semantic representation between diagnoses. And to reduce adverse drug interaction caused by combination drug use, we employ a graph convolution network to transform drug interaction information into drug interaction features. Finally, we employ the sequence generation model to learn the complex relationship among patients, diseases, and medicine and provide an appropriate medication evaluation for prescribing by doctors in small hospitals from drug list and medication course of treatment. In this paper, we leverage the MIMIC_III dataset and the dataset of a tertiary hospital in Fujian Province to verify the validity of the model. The results show that our method is more effective than other baseline methods in the accuracy of medication regimen prediction of rational medication. In addition, it has achieved high accuracy in the appropriate medication detection of prescriptions in small hospitals.

Bleomycin is an antibiotic with cytotoxic properties, commonly used in combination regimens for the treatment of Hodgkin lymphoma. The inconsistency in dosage nomenclature of bleomycin seems to be universal in many countries, which increases the risk of medication error. However, as far as we know no cases have reported. Here we present a case report of a medication error caused by bleomycin overdose. A 25-year-old patient with Stage II Hodgkin Lymphoma received a 150 USP bleomycin, which dosage was ten times higher than usually used, as part of the doxorubicin, bleomycin, vindesine, dacarbazine protocol (ABVD) at the third cycles of chemotherapy. After the medication error was found, the patient was immediately treated with intravenous rehydration and furosemide to promote clearance of drugs. To prevent lung injury, the methylprednisone and acetylcysteine was given. The patient developed a slight nausea and a mild rash, which gradually improved after the treatment. After the evaluation with PET-CT, the patient received four cycles of AVD chemotherapy. During the treatment and one-year follow-up period, no other obvious abnormalities were observed. The toxicities, clinical managements and selection of further chemotherapy after bleomycin overdose deserved serious attention in this case. More importantly, the management measures after this error can be used for reference in other hospitals.

AIMS The aim of this study was to explore whether inflammation, reflected by the C-reactive protein (CRP) concentrations affected the VRC plasma concentration in hospitalized Chinese children and adolescent patients. METHODS Medical records of inpatients were reviewed retrospectively. A linear regression analysis was performed to assess the relationship between CRP values and VRC plasma trough concentration. RESULTS Fifth-nine patients aged 1-18 years were included. A total of 90 VRC trough concentrations were included in the linear regression. The plasma trough concentration of VRC increased with the CRP concentration (n=90, r=0.377, P<0.001). VRC trough concentrations in patients with the group of moderate inflammation (3.09 (0.12~8.58); n=30) were significantly (P=0.011) higher than the group of mild inflammation (1.53 (0.01~9.35); n=60). There were no significant difference (P=0.865) in VRC trough concentration between patients with the group of mild inflammation (≤40 mg/L, n=30) and moderate inflammation (41-200 mg/L, n=6) in patients aged<12 years. VRC trough concentrations were significantly higher (P=0.032) in patients with the group of moderate inflammation (41-200 mg/L, n=24) compared to the group of mild inflammation (≤40 mg/L, n=30) in patients aged ≥12 years. When CRP concentration increased 1 mg/L, the VRC trough concentration increased by 0.010 mg/L and 0.009 mg/L in the unadjusted (95% confidence interval (CI), 0.005 to 0.016 mg/L) and adjusted (95% CI, 0.001 to 0.016 mg/L) linear regression analyses, respectively. CONCLUSIONS Inflammation response appears to provide an explanation for some of the variability in VRC exposure.

As a clinical pharmacist and clinical pharmacologist for about 25 years at the Food and Drugs Administration (FDA), I have always wondered about the question of splitting the tablet, and especially for tablets for the drugs with Narrow Therapeutic Index (NTI). For these drugs, any small increase in the amount ingested to a severe patient has risky consequences, especially in the elderly. I worked on this NTI project during my tenured year at the FDA. I reviewed over 200 commonly prescribed drugs, from the efficacy and safety perspective. My focus was identifying the Maximum Toxic Concentration (MTC), the Minimum Effective Concentration (MEC), Maximum Dose (Max D), and Minimum Dose (Min D). The therapeutic index (TI) was measured from the following equation: TI =MTC/MEC for all drugs. Also, I identified the various strengths available for each drug product and the scoring (if any). The analysis shows that the mean and standard deviation (SD) for all 64 scored tablets was 5.030 (± 2.79 units) and that all unscored drugs was 9.520 (± 14.22 units). As noted, there was more variability in the unscored tablets. This provided evidence that the drugs tending to be NTI were scored to titrate. However, patients, especially elderly, appear to be confused and having difficulty in accurately breaking the tablet scores. However, it is important to note that acetaminophen represents wide TI, maximum daily dose of 4,000 mg/day, and it is no-scored. However, levothyroxine which represents drug with NTI has 12 strengths and all are scored.

Aim Several cases of ertapenem-related neurotoxicity has been published in the current literature. However, studies evaluating the ertapenem blood concentration as a risk of these adverse events are scarce. We aimed to evaluate the relationship between the ertapenem concentration and the risk of neurological toxicity. Methods Retrospective study, including patients who underwent ertapenem treatment between october 2019 and february 2021. We excluded critical patients and those whose blood sample were not properly took in order to analyze ertapenem trough concentration. We also excluded patients whose clinical follow-up was not properly realized for the entire period of ertapenem treatment. The main outcome was the presence of any suspicious neurological side effect owing to ertapenem administration and its relationship with the plasma concentration. Secondary outcomes were to identify other clinical and analytical data contributing to a higher risk of neurotoxicity. Results Cohort was initially composed by 158 individuals. For the final analysis we evaluated 102 patients, reporting a neurological alteration in 13/102 (12.7%). Mean ertapenem trough plasma concentration was significantly higher in patients showing neurotoxicity in comparison with those who did not (37.8 mcg ml-1 SD±35.7 vs 14.6 mcg ml-1 SD±15.2; p=0.002). In multivariable logistic regression analysis, ertapenem plasma concentration (OR= 1.07; p=0.006), a moderate renal insuficiency (OR= 9.2; p=0.02) and a history of previous neurologic disease (OR=9.9;p=0.02) were identified as risk factors of neurological alteration during ertapenem treatment. Conclusions Identifying properly patients who may accumulate the antibiotic by determining their plasma levels could be helpful to minimize the risk of neurotoxicity.

Introduction: In breast cancer, adjuvant endocrine therapy improves treatment outcomes. Though, not the whole patients completed their scheduled treatment protocols. This study aimed to assess adherence to oral hormonal therapy in Egyptian breast cancer patients. Patients and methods: From February 2022 to May 2022, a cross-sectional study was conducted at the National Cancer Institute, Breast Cancer Hospital. An interview was conducted, along with a survey to assess the adherence of breast cancer patients to oral hormonal treatment. Adherence was measured using the Morisky Medication Adherence Scale-8 (MMAS-8). Results: The survey was completed entirely by 300 patients. There were 98.3% females and 1.7 % males among the patients. 30% of the patients belonged to this age group (40-50 years). The majority of patients were postmenopausal (90.3%). 18% have a high level of education, while 53.3% are illiterates. 50.7% of patients have other chronic diseases. 44.7% prefer to get medication information from a physician, 27.7% prefer pharmacists, and 27.7% get medication information from both. 99.7% of patients received proper medication counselling. As a result of the MMAS-8 survey, 40.3% of all patients were high adherent to their oral hormonal treatment, 32.7% of the patients have moderate adherence, and 27% have low adherence. No subgroups (gender, age, educational level, duration of endocrine therapy, Breast cancer stage, or other co-morbidities) were significantly associated with adherence level. Conclusion: This study demonstrates significantly high and moderate adherence to oral endocrine therapy. Reasons for this could include proper medication counselling in the setting and regular patients’ follow-up.

Background: Meta-analysis results of observational studies show that metformin can prolong progression-free survival and overall survival in cancer patients However, these studies do not strictly distinguish whether patients have type 2 diabetes or not Therefore, whether metformin adjuvant chemotherapy can improve the prognosis of non-diabetic tumor patients still needs further verification Methods: Embase、Pubmed and The Cochrane library was systematically searched for metformin and tumor subject words and free words. Extract PFS,OS and other related data according to the eligibility criteria. The pooled data were analysed by meta-analysis using Revman 5.4 to assess the efficacy and safety of metformin application. Results: A total of 3228 articles were retrieved from the database. After screening, a total of 13 studies and 1255 patients were included in meta-analysis. All included studies were randomized controlled trials. Metformin combined with adjuvant chemotherapy did not improve progression-free survival (HR=0. 01, 95CI-0. 24-0.26) ，overall survival (HR=-0. 03, 95% CI-0. 32-0.26) and not increase the objective response rate of patients. There was no significant difference in the occurrence of grade 3-4 adverse reactions compared with placebo Conclusions: Our findings suggest that chemotherapy combined with metformin may not be beneficial in patients with non-diabetic tumors, especially in patients with non-small cell lung cancer, Therefore more high-quality randomized controlled trials are needed to verify the positive effect of metformin in chemotherapy in non-diabetic tumors patients.

Objective: To evaluate the safety and efficacy of antidepressants and antiepileptic drugs in the treatment of neuropathic pain. Methods: Cochrane library, PubMed, Embase, CNKI, Wanfang, and other databases were searched using RevMan 5.3 software for data analysis to collect randomized controlled studies comparing antiepileptics and antidepressants for neuropathic pain. Results: This study enrolled a total of 1073 participants in 16 randomized controlled trials. Antiepileptic drugs and antidepressants ought to improve neuropathic pain patients’ treatment scores [OR=1.10, 95% CI(0.64 to 1.89), P =0.74], pain relief rate [OR=1.10, 95% CI(0.64 to 1.89), P =0.74], and incidence of adverse reactions [OR=0.94, 95% CI(0.48 to 1.85), P =0.87] without showing a statistically significant difference; The results of the single-agent study revealed that only pregabalin, as opposed to venlafaxine, had a significant effect on pain scores; the subgroup analysis revealed that publication bias had no effect on the study’s findings. The heterogeneity may stem primarily from different follow-up durations and drug types. Conclusion: There is no clear distinction between adverse effects and effectiveness.

Cardiotoxicity is the most dramatic complications of cancer therapies, leading to halt in potentially life-saving anti-tumor treatment regimens and a poor survival prognosis in a non-negligible percentage of patients. Angiotensin converting enzyme inhibitors (ACEIs) and β-blockers are effective in the treatment of the cancer therapy–related cardiac dysfunction (CTRCD), while their roles in the prevention of cardiotoxicity are unclear. Sacubitril/valsartan was advantageous over ACEI in heart failure patients for further reduction of cardiovascular death or heart failure re-hospitalization. However, there is short of well-established testimony of its efficacy and safety in the prevention and treatment of CTRCD in the cardio-oncology setting. Although some small observational studies found a good performance of sacubitril/valsartan in patients with CTRCD, large-scale prospective clinical studies are required to confirm its excellent results. In this paper, we review the potential benefit of sacubitril/valsartan in human subjects with CTRCD.

Background and Purpose: Invasive mucormycosis is a fatal disease caused by Mucorales species. Treatment therapy for CAM includes aggressive surgical debridement and systemic antifungals in Amphotericin B and Posaconazole as step-down therapy in the follow-up period. Despite being on oral antifungal Posaconazole therapy, patients have been observed to have a recurrence of mucormycosis in the follow-up period. Experimental Approach: An ambispective cohort study was done in the department of ENT and Pharmacology of All India Institute of Medical Sciences (AIIMS), Bhubaneswar, from April 2021 to September 2022. It includes patients on follow-up on the step-down therapy of Posaconazole. Medication adherence was measured based on the half-life of Posaconazole and participants not skipping a single dose. Key Results: The demographic data between the recurrence and non-recurrence groups, including age, sex and duration of stay, was not significant. Recurrence in mucormycosis was not found to be associated with medication adherence. By both methods of calculating medication adherence, the results were statistically insignificant. The difference in onset of recurrence of the disease between the two groups was statistically significant, with a p-value of 0.027 in patients who did not skip a single dose of Posaconazole with a hazard ratio of 3.887. There was a statistically significant difference in cost-effective analysis with a p-value of 0.042 between groups. Conclusion and Implications: Posaconazole medication adherence in the postoperative period does not affect the recurrence of mucormycosis during step-down therapy. However, it helps prolong the onset of disease recurrence in patients adhering to the medication.

Setting-up a high quality and efficient pharmacovigilance (PV) system in multi-country clinical trials can be more challenging for academic sponsors than for industrials. Generating high-quality safety data, compliant with legal and regulatory standards such as European or World Health Organization (WHO), places special requirements on the PV system. The scenario becomes more complicated when dealing with multi-country European clinical trials where heterogeneity on safety process can be encountered. Some Sponsors face these challenges are even more difficult for pediatric trials. A possible solution to ensure that the safety of all participants is equally guaranteed and the PV system fulfills all regulations could be to set up a centralized PV system. This paper introduces the key points to consider when implementing and organizing such system in multi-national European clinical trials. It is based on the Inserm-ANRS MIE pharmacovigilance department’s experience and aims to harmonize and anticipate the needs, in particular by implementing safety procedures and a network of local safety officers. This system is very useful to respond to the challenges of a European clinical trial, notably when considering the complexity of local safety requirements of each country, signal management and the specificities of paediatric regulation.

Background: Since the 2002 SCAR study, erythema multiforme(EM), a post-infectious disease, has been distinguished from Stevens-Johnson syndrome (SJS), drug-induced. Nevertheless, EM cases are still reported in the French pharmacovigilance database (FPDB). Objectives: To describe EM reported in the FPDB and to compare the characteristics of the reports. Methods: This retrospective observational study selected all EM cases reported in the FPDB over two periods: period 1 (P1, 2008-2009) and period 2 (P2, 2018-2019). Inclusion criteria were 1) a diagnosis of clinically typical EM and/or one validated by a dermatologist; 2) a reported date of onset of the reaction; and 3) a precise chronology of drug exposure. Cases were classified confirmed EM (typical acral target lesions and/or validation by a dermatologist) and possible EM (not-otherwise-specified target lesions, isolated mucosal involvement, doubtful with SJS). We concluded possible drug-induced EM when EM was confirmed, with onset ranging from 5 to 28 days without an alternative cause. Results: Among 182 selected reports, 140(77%) were analyzed. Of these, 67(48%) presented a more likely alternative diagnosis than EM. Of the 73 reports of EM cases finally included (P1, n=41; P2, n=32), 36(49%) had a probable non-drug cause and 28(38%) were associated with only drugs with an onset time ≤4 days and/or ≥ 29 days. Possible drug-induced EM was retained in 9 cases (6% of evaluable reports). Conclusions: This study suggests that possible drug-induced EM is rare. Many reports describe “polymorphic” rashes inappropriately concluded as EM or post-infectious EM with unsuitable drug accountability subject to protopathic bias.

Aim: To determine the type, cause, severity and associated factors of DRPs in CKD patients, and then to assess the results of interventions by clinical pharmacists. Methods: A cross-sectional study was carried out to review all medication orders for hospitalized patients with CKD from April to September 2022. Pharmaceutical Care Network Europe classification (PCNE) V9.1 was used to classify the DRPs; Logistic regression models were used to estimate the factors of DRPs. Results: 176 patients with CKD stage 3-5 were included, and 249 DRPs were identified in 73.9% (130/176) of participants. The most common type of problem and cause respectively were “treatment effectiveness” (52.2%, 130/249) and “drug selection” (63.1%, 157/249). 84.7% (211/249) of the DRPs were rated at severity categories B to D (causing no or potential harm), whereas 15.3% (38/249) were rated as categories E to H (causing actual harm). Clinical pharmacists proposed 433 interventions, of which 89.4% (387/433) were entirely accepted and implemented, and solved 83.1% (207/249) DRPs. The probability of having at least one DRP was higher in patients treated with ten or more drugs (AOR 4.126, 95% CI 1.754-9.705, P=0.001), with CKD stages 5 (AOR 4.954, 95% CI 1.754-9.705, P=0.005), and with diabetes (AOR 4.224, 95% CI 1.889-9.445, P<0.001). Conclusions: DRPs are common in hospitalized CKD patients, and pharmacists play a significant role in optimizing medication therapy by identifying and resolving DRPs. The number of drugs, stage of CKD and diabetes are risk factors for DRPs, and we should pay attention to this specific group.

Background: Qilong capsule (QLC) is a traditional Chinese medicine commonly used to treat ischemic stroke (IS). But the pharmacodynamic mechanism of QLC is not clear. Method: we used an existing zebrafish model to explore the protective mechanism of QLC on IS. We treated normally-developing zebrafish larvae with QLC and ponatinib 2 days post fertilization, and used the area of cerebral vascular thrombosis, red blood cell staining intensity, and brain cell apoptosis to quantitate QLC efficacy against IS. Real-time quantitative polymerase chain reaction (qPCR) was used to detect changes in the expression of genes involved in coagulation, inflammation, vascular endothelium, and apoptosis. Result: We found that QLC reduced the area affected by ponatinib-induced cerebral vascular embolism, erythrocyte staining intensity, and the number of apoptotic brain cells. qPCR showed that QLC inhibited the expression of genes related to coagulation, inflammation, and apoptosis. Conclusion: QLC had a significant protective efficacy in ponatinib-induced IS.

Background: Infections are common complications after stroke and associated with unfavorable outcomes. We evaluated the efficacy and safety of prophylactic antibiotics for post-acute stroke infection. Methods: We searched PubMed, Embase, the Cochrane Library, SinoMed, China National Knowledge Infrastructure, and WanFangData from inception to February 15th, 2022. We calculated the pooled risk ratio (RR) and mean differences (MDs) with 95% confidence interval (CI), evaluated the risk of bias and conducted sensitivity analysis with RevMan version 5.4.1 and Stata version 14.0 software. The overall quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results: Twelve studies (4809 participants) were included in this meta-analysis. There was no significant difference in the mortality rate [RR 1.03 (95% Cl: 0.91-1.16)], pneumonia [RR 0.94 (95% CI: 0.79-1.11)], and the incidence of adverse events between the prophylactic antibiotics and control groups. Prophylactic antibiotics significantly reduced the incidence of infections [RR 0.72 (95% Cl: 0.58-0.89)], and urinary tract infections [RR 0.39 (95% Cl: 0.3-0.49)] in patients with acute stroke. We performed a subgroup analysis and found a decreasing trend in pneumonia in patients with early prophylactic use of antibiotics within 24 hours after admission [RR 0.81 (95%CI: 0.62-1.07)] as compared with those using prophylactic use of antibiotics within 48 hours after admission [RR 0.94 (95%CI: 0.79-1.11)]. Conclusions: Prophylactic antibiotics did not significantly reduce the mortality rate and pneumonia in patients with acute stroke but reduced the incidence of infections and urinary tract infections.

Reactivation of the scar resulting from intracutaneous injection of Bacillus Calmette-Guérin (BCG) is a common specific reaction in Kawasaki’s Disease. It has also sporadically been associated with viral infections, Multisystem Inflammatory Syndrome in Children, influenza vaccination and mRNA COVID-19 vaccination. Since the start of the COVID-19 vaccination campaign in January 2021, the Netherlands Pharmacovigilance Centre Lareb has received 22 case reports of BCG reactivation after vaccination with a COVID-19 vaccine. In 20 case reports it concerned mRNA COVID-19 vaccines Moderna (14) and Pfizer (6). In 2 case reports the viral vector COVID-19 vaccine AstraZeneca was administered. Erythema and pain were the most frequently reported symptoms and the size of the inflammation was between 1.5 to 5 cm. BCG reactivation occurred with a median time to onset of 2 days after the second or booster COVID-19 vaccination, whereas the median time to onset was 7 days after the first COVID-19 vaccination. None of the BCG reactivations were treated. The exact mechanism of the occurrence of this specific reaction remains unknown, however involvement of heat shock protein 65 is suggested. BCG reactivation is a non-serious, self-limiting reaction that can occur after vaccination with both mRNA and viral vector COVID-19 vaccines.