Background Clinical pharmacy is an effective pharmaceutical discipline in drug therapy management and in preventing iatrogenic events. Clinical pharmacy studies in the medical device context are, however, rare in the current literature. Purpose The purpose of this study is to prove that clinical pharmacy is effective in the medical device context by reducing PICC line complications post-implantation. Methods CLIPICC is a prospective before-and-after single-centre study conducted in a University Hospital. The study comprised two successive phases: an initial observational phase (OP), where no clinical pharmacy activities were carried out, followed by an interventional phase (IP), where clinical pharmacy activities were implemented along the patient’s hospital and primary care pathway. The key outcome of the study was the number of complications per month and per patient in each phase. Comparisons were made using negative binomial regression. Univariate and multivariate analyses were performed with R software. Results A total of 138 patients were enrolled in the study. In the OP, 40 patients (59.7%) presented at least one complication with 80 complications being recorded overall in 67 patients. In the IP, 30 patients (45.5%) had at least one complication with a total of 39 complications documented in 66 patients. The number of complications per patient and per month was halved in the interventional phase. Conclusion Clinical pharmacy interventions along the entire care pathway are effective in preventing complications following implantation of PICC lines. Trial registration: NCT04359056.

Abstract Aim: We aim to compare nephrotoxic spectrum of IOCM and that of LOCM in a more intensive and comprehensive perspective using the real-world database. Methos: This is an observational, retrospective, pharmacovigilance study based on Vigibase. 7 products (iodixanol, iohexol, iopamidol, iopromide, iobitridol, ioversol and iomeprol) of ICM were included. Variable matching method was used for deduplication procedure. Two data mining method, reporting odds ratio (ROR) and bayesian confidence propagation neural networks of information components (IC) were used to detect signals for the full database, gender stratums (male and female), age stratum (0 to 64 years, 65 to 74 years and 75 or more years) and pooled analysis of total renal adverse events (AEs). Package ‘base’, ‘utils’ and ‘pheatmap’ of R language (version 4.1.2) were used to perform analysis and plot figures. Results: We got 2703 ICSRs and 3155 renal AE reports. The five most frequently reported were acute kidney injury, renal failure, renal impairment azotaemia and anuria. All ICM had highest signal value detected in age ≥75 years. Iodaxinal and iohexol had most signals detected. In pooled analysis of renal AEs, no signals detected for iopamidol, iomeprol and iopromide in the full database stratum. Conclusion: No evidence approved IOCM has safer nephrotoxicity than LOCM. CIN spectrum varies a lot within LOCM. Regarding to the whole population, not all products of ICM, such as iopamidol, iomeprol and iopromide, is likely to cause CIN.

C. Abstract AIM: Sevoflurane is an ether-based inhalational anesthetic that induces and maintains general anesthesia. Our study aimed to detect sevoflurane-induced nephrogenic diabetes insipidus using Data Mining Algorithms (DMAs) and molecular docking. The FAERS database was analyzed using OpenVigil 2.1 for disproportionality analysis. Methods: We analyzed FAERS data from 2004 to 2022 to determine the incidence of nephrogenic diabetes insipidus associated with sevoflurane. Reporting Odds Ratios (RORs) and Proportional Odds Ratios (PRRs) with 95% confidence intervals were calculated. We also used molecular docking with AutoDock Vina to examine sevoflurane’s binding affinity to relevant receptors. Results: A total of 554 nephrogenic diabetes insipidus cases were reported in FAERS, of which 2.5% (14 cases) were associated with sevoflurane. Positive signals were observed for sevoflurane with reporting odds ratios (ROR) of 76.012 (95% CI: 44.67-129.35) and proportional odds ratios (PRR) of 75.72 (Chi-sq: 934.688). Of the 14 cases, 50% required hospitalization, 14% resulted in death, and the remaining cases were categorized as other outcomes. Molecular docking analysis showed that sevoflurane exhibited high binding affinity towards AQP2 (4NEF) and AVRP2 (6U1N) with docking scores of -4.9 and -5.3, respectively. Conclusion: Sevoflurane use is significantly associated with the incidence of nephrogenic diabetes insipidus. Healthcare professionals should be cautious when using this medication and report any adverse events to regulatory agencies. Further research is needed to validate these findings and identify risk factors while performing statistical adjustments to prevent false-positives. Clinical monitoring is crucial to validate potential adverse effects of Sevoflurane.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening skin reactions, often triggered by medications such as antiepileptic drugs, nonsteroidal anti-inflammatory drugs, and certain antibiotics. Carbamazepine is one of the most common antiepileptic medicine that causes SJS. A 13-year-old male with a history of 2 years of epilepsy presented with a painful rash and extensive blistering with mucous membrane involvement, along with fever and Nilkolsky sign. Based on clinical presentation and previous medication history, the patient was diagnosed with Stevens-Johnson syndrome, and carbamazepine was identified as the cause. Carbamazepine was discontinued, and the patient was given nutritional support, wound care, and intravenous fluids, along with steroid and antihistamine treatment. The patient’s symptoms improved, and he was discharged after 13 days. Physicians must be aware of the potential for life-threatening drug hypersensitivity reactions in patients taking certain medications, particularly antiepileptic drugs. A thorough history and careful monitoring are essential for the early recognition and treatment of SJS and TEN. We want to advise all physicians that for patients with a previous drug reaction to this class of medication, carbamazepine prescribing should be avoided. KEYWORDS: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), carbamazepine (CBZ), phenytoin (PHT), ADR.

Objective: To investigate the ENT department’s (OPD, IPD) antibiotic prescribing practices at a tertiary care hospital in Lucknow, India. Material and Methods: A prospective, cross-sectional, non-experimental (observational) study was performed in (OPD, IPD) department of Ear, Nose and Throat (ENT) over a period of 6 months. Result: In this study, 100 ENT patients (51 male, 49 female) were selected based on inclusion and exclusion criteria. Ear infections were the most common reason for visits (86 patients), followed by nose (7 patients) and throat infections (5 patients). The most commonly prescribed antibiotics were β-lactam antibiotics, with penicillin’s (amoxicillin with clavulanic acid) and cephalosporin’s (cefixime) being the most commonly used. Combination therapy was used in 117 patients, with an average of 1.9 antibiotics per patient per course. A total of 40 antibiotics were prescribed, with oral being the most common route of administration. Only one adverse drug reaction was reported, with a suspected link to cefixime causing an increase in rashes in one patient. The study population had comorbid conditions of anxiety, epilepsy, and anaemia. Conclusions: To conclude, our study in the university teaching hospital (IIMSR) highlighted lesser utilization of antibiotics in ENT infections, as some of the ENT infections are not due to bacteria. The majority of ENT patients admitted to the hospital appear to have bacterial infections, and most of them reacted favourably to antibiotic treatment. Majority of the patients used the regimen in accordance with the current guidelines. Keywords: Antibiotic agents, drug utilization, adverse drug reaction, ENT infection.

Abstract Background This study aimed to establish a method to determine tigecycline (TGC) in cerebrospinal fluid (CSF) and serum of 12 patients with Multidrug-resistant acinetobacter baumannii (MDRAB) central nervous system infection (CNSI) and evaluate the correlation of TGC in CSF and serum samples. Methods TGC in CSF and serum was extracted by acetonitrile and detected by HPLC-MS/MS. The separation was performed on the Waters XBridge® BEH Shield RP18 column. This method could achieve the quantification accurately in a very short time. Results For these 12 patients, the trough concentration ranges of TGC in CSF and serum at steady-state were 16.35-53.56 ng/mL and 67.76-211.9 ng/mL. The CSF-to-serum ratio of TGC at steady-state trough concentration was ranged from 21.46% to 44.46%, and the mean value was 31.61 ± 8.13%. The correlation of TGC in CSF and serum was 0.5065. CNSI might have no potential to increase the penetration ability of TGC to CSF. Conclusion The method was validated to be accurate and effective. The correlation between the concentrations of TGC in CSF and serum at steady-state was demonstrated to be positive based on quantification of TGC in bio-samples from 12 MDRAB patients.

Aims: Older adults are vulnerable to medication-related harm mainly due to high use of medications and inappropriate prescribing. This study aimed to investigate the associations between inappropriate prescribing and number of medications identified at discharge from geriatric rehabilitation with subsequent post-discharge health outcomes. Method: REStORing health of acutely unwell adulTs (RESORT) is an observational, longitudinal cohort study of geriatric rehabilitation inpatients. Potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) were measured at acute admission, and at admission and discharge from geriatric rehabilitation, using version 2 of the STOPP/START criteria. Results: 1890 patients (mean age 82.6 ± 8.1 years, 56.3 % females) were included. The use of at least 1 PIMs, or PPOs at geriatric rehabilitation discharge were not associated with 30-day and 90-day readmission and 3-month and 12-month mortality. Central nervous system (CNS)/psychotropics and fall risk PIMs were significantly associated with 30-day hospital readmission (adjusted odds ratio (AOR) 1.53; 95%CI 1.09─2.15), and cardiovascular PPOs with 12-month mortality (AOR 1.34; 95%CI 1.00─1.78). Increased number of discharge medications was significantly associated with 30-day (AOR 1.03; 95%CI 1.00─1.07) and 90-day (AOR 1.06; 95%CI 1.03─1.09) hospital readmissions. The use and number of PPOs (including vaccine omissions) were associated with reduced independence in instrumental activities of daily living scores at 90-days post geriatric rehabilitation discharge. Conclusion: The number of discharge medications, CNS/psychotropics and fall risk PIMs were significantly associated with readmission, and cardiovascular PPOs with mortality. Interventions are needed to improve appropriate prescribing in geriatric rehabilitation patients to prevent hospital readmission and mortality.

Aim: The purpose of this study was to optimize the dosing schedule of recombinant human erythropoietin (rhEPO) for perioperative autologous blood donation in patients undergoing total knee arthroplasty (TKA). Method: TKA patients receiving different dosing schedules of rhEPO were randomly divided into three groups. Group A patients were given 10,000 IU of subcutaneous rhEPO (1 ml) daily from preoperative day 5 to postoperative day 3 (9 doses); Group B patients were given subcutaneous normal saline daily from preoperative day 5 to day 3 and then subcutaneous rhEPO daily until postoperative day 3 (6 doses in total); Group C patients were given subcutaneous normal saline daily from preoperative day 5 to the day before surgery and then subcutaneous rhEPO daily from the surgery day to postoperative day 3 (4 doses). Results: A total of 180 TKA patients were included. On postoperative day 1 and 3, group A showed significantly higher Hb levels than group B and group C. The calculated blood loss was significantly greater in groups B and C than in group A on the day after surgery. Regarding total blood loss, groups B and C lost significantly more blood than group A. No case of allogeneic transfusion occurred during the trial in any of the three groups. Conclusions: A small dose of daily rhEPO from preoperative day 5 to postoperative day 3 could significantly increase perioperative autologous blood donation efficacy and slow the decline in postoperative Hb levels in TKA patients without causing extra complications.

Aim: This research aims to provide an overview of the consequences of undiagnosed non-adherence in clinical trials. Methods: This research was conducted with a mixed-methods approach. It combines a literature review and qualitative semi-structured interviews with key opinion leaders. Based on this groundwork, the consequences of undiagnosed non-adherence in clinical trials were summarized and reported in a figure. This study focused on phases II, III, and IV in ambulatory settings across a variety of therapeutic areas and indications. Results: Various consequences of non-adherence in trials were investigated. In phase II, drug efficacy may be underestimated, variability in the outcomes may be high, and a distorted picture of side effects could be reported, resulting in an uncertain impression of the investigational product’s profile, and complicating decision-making. The sponsor may need to increase the sample size of the upcoming phase III study to improve its power, representing additional costs, or even terminate the study. In phase III, similar phenomena may be observed, making demonstration of efficacy to the regulatory bodies more difficult. Lastly, in phase IV, a distortion in pharmacometrics may occur; the drug may underperform, prescriptions may be refilled less often than expected, or extra expenses may be incurred by the payers. This can result in post-marketing dose reduction, new competitors coming into the market, and eventually, product withdrawal. Conclusion: This research highlighted the many potential adverse consequences of undiagnosed non-adherence in clinical trials, including additional costs. Collecting accurate data appeared to be crucial for decision-making throughout the drug development process.

A wave of SARS-CoV-2 infection speedily emerged in Shanghai, China, since late February 2022. Paxlovid is a therapeutic hybrid of different compounds and a novel SARS-CoV-2 protease inhibitor by blocking an enzyme required for viral protein synthesis. It could reduce the risk of hospitalization or death by 89% as well as being benefit for immunocompromised and severe COVID-19 patients. Our registry study indicated that the days of viral elimination and inflammation factors, such as IL-6, IL-10 and interferon-α levels could be lowered by paxlovid. Days of viral elimination may be associated with fasting blood glucose, NK cells count, interferon-α levels. Lipids profiles should be monitored before and after treatment of paxlovid, especially for those who have uncontrolled lipid disorder.

Bacterial infections are very commonly acquired infections. Cephalosporins are broad-spectrum antibiotics used to manage a wide-variety of infections caused by gram-positive and gram-negative bacteria. The knowledge of the basic chemistry helps in understanding the pharmacokinetic, antimicrobial and toxicological profiles of cephalosporins. Cephalosporins are antibiotics with bactericidal activity which act by inhibiting the synthesis of cell wall in bacteria. The drugs of this class are classified into five generations in which the antimicrobial spectrum shifts from gram-positive bacteria to gram-negative bacteria with increasing generations of Cephalosporins. Antibiotic-producing bacteria contain a wide range of complex defense mechanisms to protect themselves from their own antibiotics and it results in the development of antibiotic resistance. The various mechanisms by which bacteria develop resistance are: production of β-lactamases, alteration of the porin channels, alteration of molecular structure of transpeptidase, and upregulation of cephalosporin efflux pumps. The new cephalosporins are the foundation for the real warning signs to open up new and interesting possibilities for serious infections in the future thereby ensuring rational selection of antibiotics for various infections.

Background: Sofosbuvir, a very effective new direct-acting antiviral agent (DAA), has revolutionized the therapeutic management of people infected with hepatitis C virus. It has a low reported rate of side effects. Leukocytoclastic vasculitis can be associated with hepatitis C but can also be induced by many drugs. We describe a case of leucocytoclasic vasculitis induced by Sofosbuvir that resolved 3 days after drug withdrawal. We observed a temporal relationship between the treatment and the onset of vasculitis. We emphasize the multidisciplinary approach to patients with hepatitis C to make the difference between drug-induced skin damage and damage caused by the virus itself. Case presentation: A 61-year-old woman, with a history of hepatitis C virus infection started treatment with the combination ledipasvir sofosbuvir in June 2020, 400 mg per day. Five weeks later, she developed a slightly itchy erythematous and symmetrical rash on lower members. The patient initially suspected the treatment and she stopped it. Histological finding revealed a diffuse neutrophile infiltration of vessel walls confirming leukocytoclastic vasculitis. These lesions disappeared completely three days after drug withdrawal without any symptomatic treatment. Conclusions: Sofosbuvir is one of the several recent drugs that should be prone to further attention.

Aims: Although voriconazole-induced hepatotoxicity has been reported previously, the direct cause-effect relationship in the real world remains to be established. The aim of this study was to investigate the association between voriconazole and hepatic dysfunction based on the FAERS database. Methods: Data from January 2004 to March 2022 in FAERS were retrieved. We estimate the association between the hepatic dysfunction and voriconazole using reporting odds ratios (RORs) for mining the adverse event report signals and compare voriconazole with the full database and other antifungal drugs. Results: 646 reports of hepatic dysfunction related to voriconazole as the primary suspect drug were collected totally. The median time to event of the hepatic dysfunction events was 8 (interquartile range [IQR] 2-28) days. 62.20% hepatic-related adverse events appeared within the first 15 days since the initiation of voriconazole administration. The overall ROR (95% CI) for hepatic-related adverse events was 6.82 (95% CI 6.26-7.42). Comparing to other antifungal drugs, the RORs for hepatic-related adverse events of fluconazole, isavuconazole and amphotericin B were 2.19 (95% CI 1.94-2.47), 2.31 (95% CI 1.66-3.33) and 1.26 (95% CI 1.08-1.48), respectively. Conclusions: We observed strong signals of higher frequency of reporting hepatic dysfunction events associated with voriconazole in the events of hepatic dysfunction. Since the risk of developing liver injury and possible hepatic dysfunction by voriconazole depends on several factors including underlying hepatic disease, close clinical and laboratory monitoring, including therapeutic drug monitoring (TDM), are essential to prevent or promptly recognize further deterioration of the hepatic function.

Aims: To improve the countermeasures of clinical trial institutions against major public health events such as COVID-19. Methods: A questionnaire was created to investigate the effects of the global static management policy against COVID-19 on clinical trials in Shanghai in 2022. And the convenience sampling combined with snowball sampling were adopted to interview clinical research coordinators (CRC) and clinical research associates(CRA) on the platform of SOJUMP as well as WeChat. Results: 156 valid questionnaires were collected, with an effective recovery rate of 93.98%. 98.07% of the respondents believed that the effects was severe. The extent of effects on different links of clinical trials was different (rank sum test P<0.01), being great on medication/follow-up (76.28% of significant effects), monitoring/audit (74.36%) and screening/admission (71.79%).The protocol deviations associated with out of visit window (experienced by 94.23% of respondents, during the static management policy), inspection (78.85%), medication (67.95%) and withdrawal (62.82%). And the interviewees reported 49.66% of the exclusion should blame the epidemic situation. The development of online-office or remote-ethics meetings alleviated the impact of lockdown policy on approval/ethics/contract and data cleaning/site closing. 90.98% of oral drugs could be sent by express delivery, but only 1.28% had the experience of online informed consent and remote inspection. Conclusions: We shall speed up the application of the intelligent clinical trial system and remote monitoring system, realize the transformation to a new model of patient-centered clinical trial, and improve the ability to cope with major public health events such as COVID-19.

Background and Purpose: β-arrestin2 plays an important role in opioid receptor signaling, but its involvement in morphine- and fentanyl-induced respiratory depression is widely debated. The aim of this study was to determine whether β-arrestin2 signaling is associated with fentanyl- and morphine-induced respiratory depression. Experimental Approach: This study investigated whether β-arrestin2 is involved in respiratory depression induced by fentanyl or morphine by inhibiting the upstream signaling molecule GRK2 and knocking out β-arrestin2 in mice, using whole-body plethysmography chambers to assess changes in respiratory function. Key Results: In the experiment of inhibiting GRK molecules, GRK inhibitors significantly improved the respiratory depression induced by morphine, but had no effect on fentanyl. In experiment of knocking out β-arrestin2, respiratory depression was significantly improved in the morphine group, but less affected in the fentanyl group. Conclusion and Implications: Our results suggested that inhibition of β-arrestin2 signaling alleviated morphine-induced respiratory depression but had little effect on fentanyl-induced respiratory depression in both models, suggesting differences in the respiratory depression mechanisms between fentanyl and morphine. This suggests that we may need to give a differentiated dosing regimen in clinical treatment of respiratory depression caused by the two drugs.

Novel Gonadotrophin Releasing Hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add-back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix, and linzagolix have assessed treatment efficacy for fibroid related heavy menstrual blood loss in comparison to placebo. Marketing authorization has already been granted by several agencies including those in Europe, the United Kingdom, and the United States. Prior to marketing authorization, the European Medicines Agency recommends that Phase III registration trails should assess treatment efficacy in a representative study population, assess relevant outcomes with a comparison to gold-standard alternative treatment options and that long-term safety data will adequately be collected. In this review, we demonstrate limitations in the trial data generated to date, namely a lack of generalizability due to the restricted population studied, the absence of any comparison to alternative treatment methods, and findings limited to specific subgroups of patients because of the type of outcomes assessed. Symptoms related to uterine fibroids adversely affect many women’s quality of life and effective medical treatments are lacking. However, despite the urgent need for effective treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness, and cost-effectiveness in a representative population compared with alternative treatment methods before introduction into mainstream clinical practice.

Introduction: A global health issue known as antimicrobial resistance (AMR) transcends geopolitical boundaries. Surgical antibiotic prophylaxis (SAP) is the process of administering antimicrobial to treat contagions as a preventative measure, avoid them before, during, and after surgery. During surgery or after surgery there may be chances of acquiring infection. Infection at the surgical site is one such complication known as surgical site infection (SSI). It is one of the problems that reoccur the most frequently in clinical setting. Surgical site infection is described as an infection that develops with in thirty days of surgery and might be deep, affecting the organs reached during surgery, or superficial, involving only the skin. SSIs are occasionally the leading cause of death following surgical treatments. So, to reduce these types of complication we use surgical antibiotic prophylaxis. Methods: PubMed, Google Scholar, ResearchGate, and healthcare system evidence were searched from 2005 to 2022 for systemic review that was published in the English language. Result: Data were extracted for all primary outcomes, 38 reviews were included, and review quality was evaluated using AMSTAR 2. The most often reported administration of antibiotic, timing, drug class, and primary result, respectively, were preoperative antibiotic administration, first generation cephalosporin usage, and surgical site infection (SSI). Results indicate that, in comparison to a placebo or no SAP, SAP may, on average, decrease SSIs. The finding showed that postoperative SAP did not differ significantly from intraoperative SAP in reducing SSI. Keywords: Surgical Antibiotic Prophylaxis (SAP), Surgical Site Infections (SSIs), Wound Classification

Health systems encourage switching from originators to biosimilars as biosimilars are more cost-effective. The speed and completeness of biosimilar adoption is a measure of efficiency. We describe the approach to biosimilar adoption at a single hospital and compare its efficiency against the English average. We additionally follow up patients who reverted to a previously used biologic, having switched to a biosimilar, to establish whether they benefitted from re-establishing prior treatment. The approach we describe resulted in a faster and more complete switch to biosimilars, which saved an additional £380,000 on drug costs in 2021/22. Of patients who reverted to their original biologic, 85% improved short-term where the concern was tolerability, and 90% where it was efficacy. Patients remained on treatment for a prolonged period after reverting. Our approach to biosimilar adoption outperformed the English average and permits patients to revert to their original biosimilar post-switch if appropriate.

Chemotherapy induced nephrotoxicity is one of the most common complications in cancer patients, especially under treatment with cisplatin containing regimens, which may require cisplatin dose reduction and in some cases discontinuation of the treatment, which interferes with treatment process. Curcumin is an antioxidant and anti-inflammatory compound and the most important active component of curcuma longa. In this study, the preventive effect of nano-curcumin oral formulation on cisplatin-induced nephrotoxicity in cancer patients was investigated. In this triple-blind clinical trial 30 cancer patients were randomly divided into the treatment group, receiving 40 mg nano-curcumin capsules (15 patients) and the placebo group (15 patients) twice a day for four chemotherapy courses. Kidney function was measured at the beginning of the study and then at the end of each course of chemotherapy. There was no significant difference in acute kidney injury occurrence rate and creatinine and blood urine nitrogen serum levels between the treatment and placebo groups at the end of each chemotherapy course. (P value>0.05) and was not effective in preventing the cisplatin induced nephrotoxicity in cancer patients in comparison with the placebo. Additional studies with different doses and durations of administration are recommended.

Aim Prevalence of potentially suboptimal prescribing and associated risk factors were investigated among older patients attending primary care via Aboriginal Community Controlled Health Services (ACCHSs). Methods Prescription medications were audited for 420 systematically selected patients aged ≥50 years at three ACCHSs in urban, rural, and remote settings. Polypharmacy, potentially inappropriate medications (PIMs), and anticholinergic burden (ACB) were estimated and associated risk factors explored with logistic regression. Results The prevalence of polypharmacy, use of PIMs, and ACB score ≥3, was 43%, 18%, and 12%, respectively. In multivariable logistic regression analyses, polypharmacy was less likely in rural (OR=0.43, 95% CI=0.24-0.77) compared to urban health service patients, and more likely in those with heart disease (OR=2.62, 95% CI=1.62-4.25), atrial fibrillation (OR=4.25, 95% CI=1.08-16.81), hypertension (OR=2.14, 95% CI=1.34-3.44), diabetes (OR=2.72, 95% CI=1.69-4.39), or depression (OR=1.91, 95% CI=1.19-3.06). PIMs were more frequent in females (OR=1.88, 95% CI=1.03-3.42), and less frequent in rural (OR=0.41, 95% CI=0.19-0.85) and remote (OR=0.58, 95% CI=0.29-1.18) patients. Factors associated with PIMs were kidney disease (OR=2.60, 95% CI=1.37-4.92), urinary incontinence (OR=3.00, 95% CI=1.02-8.83), depression (OR=2.67, 95% CI=1.50-4.77), heavy alcohol use (OR=2.83, 95% CI 1.39-5.75) and subjective cognitive concerns (OR=2.69, 95% CI=1.31-5.52). High anticholinergic burden was less common in rural (OR=0.10, 95% CI 0.03-0.34) and remote (OR=0.51, 95% CI 0.25-1.04) patients, and more common in those with kidney disease (OR=3.07, 95% CI 1.50-6.30), or depression (OR=3.32, 95% CI 1.70-6.47). Conclusion Associations between potentially suboptimal prescribing and depression or cognitive concerns highlights the importance of considered medication review and deprescribing for these patients.

Aims: To analyze the clinical characteristics and risk factors for tigecycline-induced pancreatitis (TIP) and evaluate the safety and efficiency of tigecycline use in non-TIP. Methods: A retrospective case-control study was conducted on adult and juvenile patients administered tigecycline for >3 days. The adults were classified as TIP, non-TIP (pancreatitis with other causes), and non-pancreatitis. Univariate analyses were performed to compare TIP and non-pancreatitis, and multivariate analysis was used to identify risk factors for TIP. The clinical characteristics of TIP and the safety and efficiency of tigecycline use in non-TIP were evaluated. Results: A total of 3910 patients (3823 adults and 87 juveniles) were enrolled. The adult patients comprised 21 TIP, 82 non-TIP, and 3720 non-pancreatitis. The TIP prevalences were 0.56% in adults and 1.15% in juveniles. The mean time from tigecycline use to symptom onset was 7.2 days, and all cases were mild pancreatitis. The mean time from tigecycline withdrawal to symptom relief was 3.6 days. The multivariate analysis identified comorbid renal insufficiency as an independent risk factor for TIP (odds ratio = 3.032). Among the 82 non-TIP patients, 81.7% had severe pancreatitis and 47.6% had necrotizing pancreatitis. The modified computed tomography severity score after tigecycline use was similar to that before tigecycline use, but the pancreatic enzymes and infection indices were significantly decreased. Conclusion: The prevalence of TIP was low. Comorbid renal insufficiency was as an independent risk factor for TIP. Tigecycline is safe and efficient for treatment of pancreatitis, especially necrotizing pancreatitis, with intra-abdominal infection

Aim: Nirmatrelvir as a new 3CL protease inhibitor for treating COVID-19 drug of antiviral drug, the potential side effects have not yet been fully studied yet. The aim of this study was to identify potential risk of Nirmatrelvir by analyzing post-marketing safety data based on the largest publicly available worldwide pharmacovigilance database. Methods: We analyzed Nirmatrelvir adverse events to detect and characterize relevant safety signals based on the FDA Adverse Event Reporting System database in 2022. Case/non-case approach were used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for AEs with ≥4 counts. Results: Total of 26846 cases were included. Disease recurrence [ROR(95%CI)=413.2(395.6-431.59)], dysgeusia [ROR(95%CI)=110.84(106.04-115.85)], anosmia [ROR(95%CI)=15.21(12.76-18.11)], ageusia [ROR(95%CI)=9.80(8.50-11.3)] and urticaria [ROR(95%CI)=1.91(1.69-2.17)] were the main safety signals. In addition, abdominal pain upper and skin toxicity were two specific safety signals of Nirmatrelvir. In pregnant population, a significant increased ROR was found in life-threatening [ROR(95%CI)=5.12(1.38-19.00)]. Conclusion: We identified that disease recurrence, dysgeusia, abdominal pain upper and skin toxicity were the main and specific safety signals of Nirmatrelvir. Clinician and pharmacist should pay attention on these AEs. Notably, a potential risk of Nirmatrelvir in pregnant population should be alerted.

Introduction: Reactivation of varicella-zoster virus (VZV) most commonly manifests as shingles. A few months after the start of the COVID-19 vaccination campaign cases of shingles were reported. Objective: We aimed to report cases of VZV reactivation reported after COVID-19 vaccination to the Tunisian National Centre of pharmacovigilance (NCPV). Method: This is a retrospective study of cases of VZV reactivation reported to the CNPV after COVID-19 vaccination from March 2021 to May 2022. Results: We included 20 patients with shingle. The sex ratio (M/F) was 0.8. The median age was 68.5 years. Nine patients were over 70 years of age. The administered vaccines were an mRNA vaccine for 15 patients. The onset delay ranged between one and 30 days (mean of 4.5 days). All patients recovered within a few days and no severe cases have been reported. Two patients received the second dose; One patient did not experience a recurrence of the symptomatology. The other patient, had aggravation of symptomatology and occurrence of facial paralysis; noting that the initial symptomatology did not entirely disappear when the patient received the second dose. The patient was diagnosed with Ramsay Hunt Syndrome. Conclusion: Our study draws attention to the chronological association between SARS-CoV-2 vaccine and VZV reactivation, which should be investigated.

Aims: Mirvetuximab soravtansine is the first-in-class antibody-drug conjugate approved in November 2022 for the treatment of folate receptor-α positive ovarian cancer. The aim of this study was to develop a population pharmacokinetic (PK) model to describe the concentration-time profiles of mirvetuximab soravtansine, the payload (DM4) and a metabolite (S-methyl-DM4). Methods: Mirvetuximab soravtansine was administered intravenously from 0.15 to 7 mg/kg to 543 patients with predominantly platinum-resistant ovarian cancer in three clinical studies, and the plasma drug concentrations were analyzed using a nonlinear mixed-effects modelling approach to estimate the PK parameters, inter-individual variabilities, and residual errors. Stepwise covariate modelling was performed to identify covariates. Results: We developed a semi-mechanistic population PK model that included linear and nonlinear routes for the elimination of mirvetuximab soravtansine and a target compartment for the formation and disposition of the payload and metabolite in tumor cells. The model adequately described the concentration-time profiles for the three analytes. Patient body weight, serum albumin, and age were identified as the major covariates. Exposures in patients with renal or hepatic impairment were estimated. The effect of inhibition of cytochrome P450 (CYP) 3A4 on drug exposures was also evaluated. Conclusions: There is no need for dose adjustment due to covariate effects for mirvetuximab soravtansine administered at the recommended dose of 6 mg/kg based on adjusted ideal body weight. The model also showed that dose adjustment is not required for patients with mild or moderate renal impairment, mild hepatic impairment, or when concomitant weak and moderate CYP3A4 inhibitors are used.