PRES is a rare neurological disease possibly associated with the use of calcineurin inhibitors like cyclosporine A. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, is responsible for the outbreak of coronavirus disease 19 (COVID-19) and can cause neurological manifestations. We describe a case of CSA-related PRES whose diagnosis was difficult due to concurrent infection with SARS-CoV-2. The 16-year-old patient was known to have corticosteroid-resistant nephrotic syndrome secondary to minimal change disease. CSA was therefore introduced and on the fifth day of treatment, he presented with seizures followed by fever. Biological and MRI data were in favor of SARS-CoV-2 encephalitis. Relief of immunosuppression by discontinuation of CSA was decided and the patient was put on anticonvulsants. After being declared cured of COVID-19, which was without other clinical signs, the CSA was reintroduced but the patient presented with seizures the next day. This allowed us to rectify the diagnosis and relate the seizures to a CSA-related PRES. We concluded that infection with SARS-CoV-2 could be a differential diagnosis of a PRES related to anticalcineurins.

AIMS Doxorubicin-induced cardiotoxicity (DIC) is a significant cause of mortality in cancer care. This study was conducted to establish the frequency of DIC in Zimbabwean breast cancer patients on doxorubicin and to test the DIC predictive power of genetic biomarkers. METHODS A cohort of 50 Zimbabwean breast cancer patients treated with doxorubicin were followed up for 12 months with serial echocardiography and genotyped for UGTA1A6*4, SLC28A3 and RARG. 11% of the patients experienced DIC. RESULTS The frequency of SLC28A3 (rs7853758), UGT1A6*4 (rs17863783) and RARG (rs2229774) was 60.7%, 17.9% and 14.3% respectively. No association between DIC and the three variants was observed. CONCLUSIONS This is the first study on the prevalence of DIC and associated genetic biomarker predictive evaluation in Zimbabwean breast cancer patients. The genetic frequencies observed in our study was different to that reported in other populations. A larger sample size with a longer follow up time will be necessary in future studies.

Background: TMS-007, an SMTP family member, modulates plasminogen conformation and enhances plasminogen-fibrin binding, leading to promotion of endogenous fibrinolysis. Its anti-inflammatory action mediated by soluble epoxide hydrolase inhibition contributes to the efficacy. Evidence suggests that TMS-007 can effectively treat experimental thrombotic and embolic strokes with a wide time window while reducing hemorrhagic transformation. Aims: To evaluate the safety, pharmacokinetics, and pharmacodynamics of TMS-007 in healthy volunteers. Methods: A randomized, placebo-controlled, double blind, dose-escalation study, administered as a single intravenous infusion of TMS-007 in cohorts of healthy male Japanese subjects. There were 6 cohorts planned, but 5 were completed. In each cohort (n = 8), individuals were randomized to receive one of 5 doses of TMS-007 (3, 15, 60, 180, or 360 mg; n = 6) or placebo (n = 2). Results: TMS-007 was generally well-tolerated, and no serious adverse events attributed to the drug. A linear dose-dependency was observed for plasma TMS-007 levels. No symptoms of bleeding were observed in brain MRI analysis, and no bleeding-related responses in laboratory testing were found. The plasma levels of the coagulation factor fibrinogen and the anti-fibrinolysis factor 2-antiplasmin levels were unchanged after the TMS-007 dosing. A slight increase in the plasma level of plasmin-α2-antiplasmin complex, an index of plasmin formation, was observed in some subjects who received 360 mg of TMS-007 (≈ 6 mg kg−1). Conclusions: TMS-007 is generally well-tolerated and exhibits favorable pharmacokinetic profiles that warrant further clinical development.

Aim: to design and implement a medication reconciliation protocol led by clinical pharmacists that allowed to identify, characterize and, eventually, prevent antiparkinsonian medication errors to promote therapeutic quality and safety in daily practice. Methods: This was an interventional, single-center, one-year, prospective study analyzing the impact of developing an antiparkinsonian medication reconciliation program. All the patients who were hospitalized and had, at least, one active prescription containing an antiparkinsonian drug at hospital admission were included. The medication reconciliation was performed by following a three-phased check: inpatient electronic prescription validation after assessing the outpatient medication schedule, review of the latest clinical report emitted by the Neurology Department, and pharmacist-driven interview of the patient and/or caregiver to confirm the information regarding medication gathered. Results: 171 admission episodes from 132 patients were registered between February 1, 2021, and January 31, 2022. Of 224 prescription lines involving antiparkinsonian drugs, 179 contained, at least, one medication error (59.8%). Commission errors (91.62%) were more frequent than omitted drugs (8.38%). The most common medication errors were related to timing (41.90%), frequency (21.23%), and dosing (19.55%). The implementation of the medication reconciliation program prevented the erroneous administration of 2716 antiparkinsonian doses, 60% of the total number of doses prescribed during this period. Interestingly, a significant relationship between the number of medication errors and having levodopa prescribed was evidenced (p<0.05). A contraindicated drug was prescribed in almost one-third of the episodes (29.82%). Conclusion: Clinical pharmacists’ implementation of an antiparkinsonian medication reconciliation program sharply reduced medication errors, and contraindicated drugs prescription.

Coronavirus disease 2019 (COVID-19) is the most prevalent disease in society today, and vaccination is a powerful weapon against COVID-19. However, there have been many recent reports of vaccine-induced skin side effects. Autoimmune bullous reactions caused by the COVID-19 vaccine are rare. We identified a case of refractory PV associated with COVID-19 vaccination that improved after 2 RTX injections.

Compounds Study Design Clinical Population Main Findings Reference SSRI SSRI+RAS PSM cohort study SSRI users 30,311 SSRI+RAS 30,311 A total of 49,327 1997 to 2012 Risk for psychiatric hospital contacts↓ (Köhler-Forsberg et al., 2020) ACEI ARB Nationwide population-based study in Danish 1,576,253 individuals 2005 to 2015 Rate of incident depression↓ (Kessing et al., 2019) ACEI ARB Meta-analysis of Randomized clinical trials Mental health domain of quality of life↑ (Brownstein et al., 2018) ACEI ARB 378 patients with HBP Rates of antidepressant usage↓ (Nasr et al., 2011) ACEI CCB β-blockers Nationwide Population-Based Study in Danish 5.4 million individuals 2005 and 2015 Rates of depression↓ (Enalapril, ramipril propranolol, atenolol, bisoprolol, and carvedilol user) (Kessing et al., 2020) ACEI ARB Prospective study 144,066 patients Risk of mood disorders admissions↓ Risk for mood disorder↓ β-blockers and CCB higher risk (Boal et al., 2016) Candesartan 4 mg/d orally for 3 months 17 patients with T2DM Interpersonal sensitivity↓ Depression ratings↓ Sensitivity of the adrenals to ACTH↓ Expression of AT1R↓ (Pavlatou et al., 2008)

The European Medicines Agency (EMA) started operating under its new legal mandate on 1 April 2022. The mandate brings new responsibilities to the Agency in three different areas: • Reinforcement of the role and activities of the EMA pandemic Task Force(which is now known as the Emergency Task Force (ETF)). • A stronger role of EMA in the monitoring of shortages of critical medicines, medical devices and in-vitro diagnostics, both in anticipation of and during a crisis. • A more coordinated mechanism of European Union (EU) experts advice on medical devices classified as high-risk (class IIa and III or class D (1)) and in-vitro diagnostic medical devices. Here we consider the impact of the COVID-19 pandemic on the operations of EMA and the European medicines regulatory network, and how EMA’s new mandate will strengthen the Agency’s and the Network’s ability to face crises. EMA’s extended mandate brings clear benefits in terms of response to public health emergencies at EU level, which ranges from improvements in crisis management to avoiding medicine shortages and improving access to diagnostics and medical devices that are safe and conform to their expected function.

Background: Facial angiofibromas (FAs) are common skin manifestations of tuberous sclerosis complex (TSC) that occur in up to 80% of patients. Rapamycin seems to be effective in decreasing FAs. Objective: The aim of our study was to investigate the efficacy and safety of topically applied rapamycin in TSC patients with FAs. Methods: The methods and the results were carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. PubMed/MEDLINE, SCOPUS, and Cochrane database were systematically searched until April 21, 2022, using the PICO tool (Patient, Interventions, Comparisons, Outcome). Studies regarding efficacy and/or safety of topical sirolimus for the treatment of FAs in TSC with a published full-text in English were included. Safety was assessed based on adverse effects and sirolimus’ blood levels, and efficacy was documented by clinical improvement and reduction of Facial Angiofibroma Severity Index (FASI). For Meta-analysis, Review Manager (RevMan) 5.4.1 software was used, using random-effects model and standardized mean difference (SMD) with 95% confidence interval (CI). Results: Twenty-one final studies were included. Regarding safety, in the included studies the observed adverse effects were mainly local, while the blood levels of rapamycin were within safe limits, decreasing the likelihood of systemic immunosuppression. The meta-analysis revealed a statistically significant decrease in post-treatment FASI (SMD: -1.31, 95% CI: [-1.85,-0.77], p-value <0.00001). Subgroup and sensitivity analyses indicated similar findings. No publication bias was found to this association. Conclusion: The application of topical sirolimus to FAs can safely decrease their severity in patients with TSC.

Several systematic reviews have been published on tacrolimus (TAC) population pharmacokinetic (PPK) modeling; however, most of them have focused on the transplant patient population. This study investigated TAC population pharmacokinetic characteristics in non-transplant patients through a systematic review of TAC population pharmacokinetic studies carried out in this patient population, with the aim of clarifying factors affecting TAC pharmacokinetic behavior and promoting individualized TAC-based treatment in non-transplant patients. The Cochrane Library, PubMed, and Embase databases, as well as Chinese databases (SinoMed, Wanfang, and China National Knowledge Infrastructure) and related references, were searched using a non-linear mixed-effects modeling approach, from the time of inception of the databases to July 2022, to identify TAC population pharmacokinetic studies modeled in non-transplant patients. Eighteen studies, all from Asian countries (China and Korea), were included in this study. Of these studies, 56% and 28% were carried out in pediatric and adult patients, respectively. Over half of the studies (56%) were conducted in patients with nephrotic syndrome. Combined medications, body weight, genetic polymorphisms, and physiological function were the most common covariates affecting TAC clearance, and variability in the apparent volume of distribution was largely explained by body weight. In addition, only 2 studies assessed the developed models through external evaluation. In non-transplanted patients, factors that affect TAC pharmacokinetics include combined medications, body weight, genetic polymorphisms, and physiological function. Recent investigations have focused mainly on Asian populations, and expanded trials that will use external evaluations for relevant model assessment are required to investigate generalizability to other ethnic populations.

Background: Vonoprazan-based regimens are anticipated to have higher Helicobacter pylori eradication rates than PPIs. Aim and objective: to compare between the effectiveness of two 14-day regimens; one based on vonoprazan and the other on esomeprazole, to eradicate H. pylori. Patients and methods: Participants were determined to have active H. pylori infection and were either untreated or had previously received therapy were randomly assigned to either the VAL group (vonoprazan 20 mg bid, amoxicillin 1000 mg bid, plus levofloxacin 500 mg once day) or the EAL group (Esomeprazole 20 mg bid., amoxicillin 1000 mg bid., and levofloxacin 500 mg once daily). After 4-6 weeks following the end of the therapy, an H. pylori antigen test was used to determine the degree of eradication. Results: A number of 122 individuals were randomly assigned to either the VAL (n = 61) or EAL (n = 61) groups, and 118 patients were successful in completing the study. The eradication rates of H. pylori were found to be 97.7 percent for the VAL group and 68.5 percent for the EAL group, respectively (P = 0.031). All adverse treatment-related occurrences were minor and did not differ substantially between the two groups, such as nausea and vertigo. Conclusions: The VAL regimen was well tolerated and led to increased eradication rates; as a result, VAL may be thought of as a powerful regimen for treating H. pylori, particularly in nations with high levels of antibiotic resistance.

Aim: ST-segment elevation myocardial infarction (STEMI) is usually caused by a rupture in the atherosclerotic plaque, followed by platelet aggregation which ultimately leads to acute coronary artery occlusion. In this study, we investigated the effect of maintenance dose of Eptifibatide (intravenous drug of GP IIb/IIIa inhibitor) in patients with STEMI who underwent primary percutaneous coronary intervention (PPCI). Methods: 264 patients who had acute chest pain suggestive of STEMI were entered in the study. All patients received the same dose of bolus dose of eptifibatide. Then the patients were randomly divided into two groups, one group (n=147) received a maintenance dose of intravenous eptifibatide (infusion of 2g/kg/min) and the other group (n=117) did not receive this treatment. All patients were evaluated 1 and 3 months after the start of treatment in terms of predicted outcomes. Results: The occurrence of three-month MACE between the case and control groups did not have a statistically significant difference (28.6% versus 35.0% ; P-value: 0.286). Re-hospitalization occurred in 10 patients (6.8%) from the case group and 30 patients (25.6%) from the control group, which was statistically significant (P-value: 0.000). Also, investigations showed that the rate of re-infarction (P-value: 0.024) and target lesion revascularization (P-value: 0.003) was significantly lower in the group that received Eptifibatide infusion. Conclusion: Eptifibatide maintenance dose infusion in patients who undergo PPCI in the context of STEMI, does not significantly reduce MACE, although it does significantly reduce re-hospitalization and re-infarction. It also does not increase the risk of bleeding and cerebrovascular events.

Background：There are many methods to treat subungual wart, but the treatment results are not satisfactory. Case presentation：A patient with a 10-year history of subungual warts was cured after using paiteling, and no warts recurred after six months of follow-up. Conclusion：Paiteling is effective and safe to treat subungual warts.

Aims Healthcare workers’ (HCWs) ability to recognize, classify and manage adverse reactions (ADR) is crucial to ensure patient safety. This study assessed HCWs’ awareness, knowledge, and practice on ADR. Methods This was a cross sectional online questionnaire case-based study, involving clinical HCWs at two tertiary hospitals. Results We recruited 321 respondents with 256 doctors, 58 nurses and seven medical assistants. HCWs with more than five years’ experience and dermatologists had better ADR knowledge. Three-quarter failed to recognize off-target nonimmune mediated non-steroidal anti-inflammatory drugs reactions. About 26% (n=84) could not recognize severe cutaneous adverse drug reactions (SCARs). In those who recognized SCARs, only 76.6% (n=177) will not re-introduce the implicated drugs. Knowledge in managing anaphylaxis and awareness in paradoxical drug-induced reaction was poor. About 18% (n=58) did not use adrenaline in anaphylaxis and 80% (n=259) were unfamiliar with the usefulness of tryptase in anaphylaxis. Nearly 52% were ignorant of succinylated gelatin solution as a hidden allergen. Nearly 90% (n=286) were unfamiliar with utilization of fresh frozen plasma in severe ACE-inhibitor induced angioedema. A significant proportion of respondents understood the reporting pathway for ADRs to medications and vaccines, respectively. Only up to 67.3% (n=216) understood the need to update ADR reporting when a new reaction occurred. Conclusion The overall HCWs knowledge and practice on ADRs is not satisfactory where they lacked awareness on many aspects of ADRs. These findings provide supportive evidence for the incorporation of ADR into the healthcare curricula and plan periodic programs to ensure patient safety.

Abstract There are two simple concrete methods to reduce the dosage of NSAIDs dramatically. An attending physician is suspected of being a fake doctor if the blood test is never performed after administration of the antihyperlipidemic drug. However, the analgesic effects are often not examined after the administration of analgesics. As with antihyperlipidemic drugs, efficacy should be examined after administration of analgesics. Analgesics should not be administered continuously without examining the analgesic effects. One study shows no difference in the analgesic effects between NSAIDs and acetaminophen at the latest 2 weeks after injury or surgery. If NSAIDs are administered for more than 2 weeks, it is necessary to confirm that NSAIDs are more analgesic than acetaminophen. If NSAIDs are more analgesic than acetaminophen, prolonged administration of NSAIDs is acceptable, knowing that they have more adverse effects than acetaminophen. If the analgesic effects of both medicines are comparable, acetaminophen should be administered. These are a matter of course. The two methods reduce the administration of NSAIDs dramatically, reducing the aforementioned adverse effects due to NSAIDs dramatically.

Olanzapine pamoate is an intramuscular depot injection for the treatment of schizophrenia. Approximately 1.4% of patients develop a serious adverse event called Post Injection Delirium/Sedation Syndrome (PDSS); characterised by drowsiness, anticholinergic and extrapyramidal symptoms. The objective is to investigate olanzapine PDSS presentations including clinical features and treatment approach. This is a retrospective review of olanzapine PDSS patients from three toxicology units and the NSW Poisons Information between 2017 and 2022. Adult patients were included if they had intramuscular olanzapine then developed PDSS criteria. Clinical symptoms, treatment, timing and length of symptoms were extracted into a preformatted Excel database. There were 18 patients included in the series, with a median age of 49 years (IQR: 38-58) and male predominance (89%). Median onset time post injection was 30 minutes (IQR: 11-38). PDSS symptoms predominate with drowsiness, confusion and dysarthria. Median length of symptoms was 24 hours (IQR: 20-54). Most common treatment included supportive care without any pharmacological intervention (n=10), benzodiazepine (n=4) and benztropine (n=3). In one case, bromocriptine and physostigmine followed by oral rivastigmine were given to manage anti-dopaminergic and anti-cholinergic symptoms respectively. This proposed treatment combination could alleviate some of the symptoms. In conclusion, this case series supports the characterisation of PDSS symptomology predominantly being anti-cholinergic with similar onset (<1 hour) and duration (<72hours). A combination of bromocriptine and physostigmine followed by rivastigmine is proposed to manage PDSS if patients develop severe dopamine blockade or anti-cholinergic delirium.

As a general rule in pharmacotherapy, ineffective pharmacological treatment should be discontinued. Ineffective pharmacotherapy should not be administered for a long time. The first problem is the appropriate duration to determine that the pharmacological treatment is ineffective. The second problem is the criterion for determining the efficacy (or ineffectiveness) of the pharmacological treatment. As far as I know, there is no evidence regarding the duration. Nevertheless, it is necessary to determine the duration. Standards by academic organizations are necessary, even provisional standards are acceptable. Long-term administration of ineffective medicine causes the problem of adverse effects. It loses the opportunity to receive effective treatment. In case that HT is ineffective for menopause, the treatment of fibromyalgia may relieve symptoms of menopause. Patients do not get medical attention for the improvement of abnormal hormone levels but do for the improvement of subjective symptoms such as widespread pain, numbness, insomnia, and fatigue. Some people are almost asymptomatic even if their hormone levels are abnormal. I believe that the efficacy (or ineffectiveness) should be determined with the improvement of the above-mentioned subjective symptoms rather than the improvement of the abnormal hormone levels.

The lung is one of the most commonly encountered sites of Scedosporium infection. Due to its intrinsic resistance to all current antifungal agents, treatment of Scedosporium infections still remains a great challenge. Voriconazole has been recommended to the first-line systemic treatment of Scedosporium infections, but the duration is not well recommended, especially for immunocompetent patients. This case series presented our experience on diagnostic, manifestation, and treatment strategies of Scedosporium pneumonia. The case records of non-Transplanted non-HIV adults with Scedosporium pneumonia hospitalized in our Hospital from January 2020 to February 2022 were retrospectively analyzed, and their case characteristics, antifungal therapy drug selection and treatment course were summarized: All 3 patients had underlying lung disease, 2 female patients had a history of bronchiectasis, and 1 male patient had a history of emphysema. Both female patients had a mixed infection with Scedosporium and nontuberculous mycobacteria. In one female patients, Scedosporium was no longer detected after 2 months of treatment with voriconazole, and the clinical symptoms were improved than before, with no significant change in imaging. In one female patient, although Scedosporium was still isolated from sputum after 12 months with voriconazole treatment, the symptoms were improved than before, and antifungal therapy was discontinued after no significant improvement 1 and a half months after switching to Posaconazole. In one male patient, Scedosporium was no longer detected after 3 months treatment with voriconazole, and the clinical symptoms and imaging were significantly improved. Three patients had voriconazole concentrations between 1.1-2.8 μg/mL during treatment.

Pregabalin is an anti-epileptic drug which also represents one of the most frequently prescribed medications for neuropathic pain management worldwide. Moreover, in recent years its use has widely increased also in critically ill patients in the setting of multimodal analgesia. Commonly available as capsules and oral solution, it is characterized by a predominant kidney elimination. Consequently, in patients with kidney failure posology adjustments are needed. According to the pharmacokinetic parameters (low molecular weight and volume of distribution, negligible protein binding), pregabalin is expected to undergo a significant extracorporeal clearance, which should be taken into account when one of the different Kidney Replacement Therapy (KRT) modalities is required for Acute Kidney Injury (AKI). The case of a critically ill patient with AKI undergoing Therapeutic Drug Monitoring of Pregabalin in course of Continuous, Prolonged Intermittent KRT (CKRT and PIKRT, respectively), and conventional intermittent hemodialysis (IHD) is presented here for the first time.

Aim: The effectiveness and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with stage III chronic kidney disease (CKD) are still subject to debate. We therefore assessed and compared the effectiveness and safety of DOACs vs. warfarin in this population. Methods: A cohort of patients with an inpatient or outpatient code for AF and stage III CKD who were newly prescribed an oral anticoagulant (OAC) was created using administrative databases from the Quebec province of Canada between 2013 and 2017. The primary effectiveness outcome was a composite of ischemic stroke, systemic embolism, and death, whereas the primary safety outcome was a composite of major bleeding within a year of DOAC vs. warfarin initiation. Treatment groups were compared in an on-treatment analysis using inverse probability of treatment weighting and Cox proportional hazards. Results. A total of 8,899 included patients filled a new OAC claim: 3,335 for warfarin and 5,564 DOACs. Compared with warfarin, rivaroxaban 15 mg and 20 mg presented a similar effectiveness and safety composite risk. Apixaban 5.0 mg was associated with a lower effectiveness composite risk (Hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.65–0.88) and a similar safety risk (HR 0.94; 95% CI 0.66–1.35), whereas apixaban 2.5 mg was associated with a similar effectiveness composite (HR 1.00; 95% CI 0.79–1.26) and a lower safety risk (HR 0.65; 95% CI 0.43–0.99). Conclusion: In comparison with warfarin, rivaroxaban and apixaban appear to be effective and safe in AF patients with stage III CKD.

Mucormycosis was an acute and invasive fungal infection with a high mortality rate. The treatment of mucormycosis was challenging. And the incidence of the mucormycosis seems to be increasing. The key to Mucormycosis therapy not only depend on anti-Mucor infection, but also included the management of some risk factors. Liposomal amphotericin B (L-AMB) was the first line drug to treat mucormycosis. The dosage regimen recommended by the guideline was often associated with higher nephrotoxicity and morbidity. A pharmacokinetic/pharmacodynamic (PKPD) model was conducted to evaluate suitable dosage regimens in Mucormycosis patients. 10mg/kg/day LAMB recommended in the guidelines might not be needed. 5mg/kg/day LAMB might be sufficient to achieve the target value of PKPD and indicated a good anti-Mucor effect. Successful management of mucormycosis was also based on suitable management of several risk factors which played a very important role in the progression of mucormycosis, such as iron factor, diabetes mellitus with acidosis and thrombosis. Application of deferasirox, statins and keep platelet level might be promising approaches in mucormycosis therapy.

A 42-year-old female, treated with isoniazid, rifampicin, pyrazinamide and ethambutol for multifocal tuberculosis, developed, forty days later, hyperthermia, facial edema, cervical lymphadenopathy and generalized exanthema. Biological test results revealed eosinophilia, atypical lymphocytes, thrombocytopenia and liver injury. DRESS was suspected, and four antituberculosis drugs (ATD) were withdrawn. As patch tests for the four ATD showed negative results, we decided to reintroduce pyrazinamide, ethambutol and rifampicin separately with a three-day interval. Pyrazinamide and rifampicin were tolerated by the patient. However, six hours after receiving ethambutol, she developed fever and generalized rash, with no biological abnormalities, which resolved two days later. Since ethambutol was claimed to be the culprit drug, isoniazid was added, and 10 hours later, the patient developed fever, facial edema, generalized rash, eosinophilia and liver injury. This clinical and biological pattern resolved two weeks later. This report suggests a hypersensitivity relapse to ethambutol after isoniazid-induced DRESS in patients treated with first-line ATD.

Little is known about morbidity due to drug-related hyponatraemia, despite hyponatraemia being a common side effect of frequently prescribed medicines. We conducted a 12-month retrospective service evaluation of hospital admissions due to drug-related hyponatraemia to determine what drugs are contributing factors, describe patient demographics and burden of morbidity. This was undertaken at a large acute UK hospital and drug-related hyponatraemia was defined by admissions where hyponatraemia was coded as the principal diagnosis and specific medication(s) were recorded as either contributory factor(s) or the principal cause of hyponatraemia and these medication(s) were discontinued. Of 131 hyponatraemia admissions, 71 (54%) were drug-related. Angiotensin converting enzyme inhibitors/ angiotensin receptor blockers, proton pump inhibitors and thiazide diuretics were drug classes most commonly associated. 61% of patients were women, median age 81 (IQR15.5) years, 61% were on more than 2 implicated drugs. The median length of stay was 4 (2-9 days IQR). This study highlights that elderly woman on more than 2 drugs that can cause hyponatraemia, constituted the majority of patients admitted to hospital with drug-related hyponatraemia.

Acute liver injury with special clinical phenotype after use of herbal Runzaozhiyang capsulesRunning Head: Liver injury caused by Runzaozhiyang capsulesJiabing WangTaizhou Municipal Hospital, Zhejiang, Taizhou 318000, ChinaE-mail address: wangjiabing9205@163.comKeywords: Runzaozhiyang capsules; Acute liver injury; Herbal; Case report

Aim Assess the effectiveness and safety of nivolumab versus cetuximab in patients with R/M HNSCC, as well as to analyze possible prognostic factors for response to treatment with nivolumab. Methods We conducted an observational, retrospective, descriptive study of patients with R/M HNSCC who initiated treatment with nivolumab or cetuximab monotherapy in two periods of equivalent duration. Overall efficacy was measured in progression-free survival (PFS) and overall survival (OS); safety was evaluated using the CTCAE (Common Terminology Criteria for Adverse Events) classification version 5.0 of the National Cancer Institute (NCI). Results Median overall survival (OS) was 9.1 months with nivolumab (n=34) vs. 6.3 months with cetuximab (n=12)(HR=0.5; 95%CI: 0.24-1.03; p=0.058). Progression free survival (PFS) were 4.3 for nivolumab and 4.65 months for cetuximab (HR=0.59; 95%CI: 0.29-1.19; p=0.14). Any grade adverse events (AEs) were reported in 97% and 100% of the patients treated with nivolumab and cetuximab. Serious AEs were observed in 26% and 58% of the patients respectively. Elevated albumin values, lymphocytosis, neutropenia and elevated neutrophil/lymphocyte ratio values have positive prognostic value on the response to nivolumab in R/M CCECC. Conclusion Effectiveness of nivolumab in terms of OS remains superior to cetuximab. OS, PFS and severe or any grade AEs were superior in both arms of our study than in the clinical trials. The AEs profile of nivolumab differs in our study from the clinical trials’ observations. We have identified four positive statistically significant prognostic variables on the response to nivolumab in R/M HNSCC.