Aim: This systematic review and meta-analysis assessed the effects of pharmacist interventions in Asian health care environments on hospitalization, mortality, and quality of life (QoL) among older people in Asia. Methods: A comprehensive search was conducted across 5 databases, encompassing studies from inception until December 2021. Only studies involving pharmacist interventions for people aged 65 years or older, residing in Asian countries, were considered. Studies without evidence of pharmacist involvement or conducted outside of Asia were excluded. Data extraction was independently performed by two reviewers, capturing key study characteristics, pharmacist intervention types, and outcome measures for subsequent meta-analyses. Forest plots were generated using a random effects model to obtain risk ratios or pooled standardized mean differences (SMD). Results: A total of 142 articles underwent thorough review, and ultimately, eight studies meeting the inclusion criteria were included in the meta-analyses. These studies encompassed diverse healthcare settings such as outpatient, inpatient, and nursing homes, with sample sizes ranging from 32 to 306 older adults. Pharmacist interventions were found to significantly reduce hospitalization rates (n=4, risk ratio: 0.64, 95% CI: 0.42-0.98) and mortality rates (n=4, risk ratio: 0.59, 95% CI: 0.38-0.92) among older people. However, the analysis did not reveal a significant improvement in QoL compared to usual care (n=5, SMD: 0.37, P = 0.208). Conclusions: These findings highlight the crucial role of pharmacists within healthcare teams in Asian countries. Pharmacist interventions have an impact on reducing hospitalization and mortality rates among the elderly, underscoring the importance of optimizing patient outcomes in Asia.

Aims: To analyze and compare the adverse events (AEs) and adverse drug reaction (ADRs) associated with pirfenidone and nintedanib, two antifibrotic drugs commonly used in the treatment of idiopathic pulmonary fibrosis (IPF), based on real-world data. Methods: We collected reports from the FD Adverse Event Reporting System (FAERS) and VigiAccess databases. Two main disproportional analysis, including reporting odds ratio (ROR) and proportional reporting ratio (PRR), were conducted to determine the association of these drugs with signals at both the preferred term (PT) and system organ class (SOC) levels. Results: A total of 55,949 reports for pirfenidone and 35,884 reports for nintedanib were obtained from the FAERS database. Correspondingly, the VigiAccess database provided 37,187 reports for pirfenidone and 23,134 reports for nintedanib. Male patients and individuals over the age of 65 were more likely to report AEs for both drugs. Gastrointestinal disorders emerged as the most significant signal at SOC level for both pirfenidone and nintedanib. Additionally, signals such as nausea, diarrhoea and decreased appetite were notable at PT level. Furthermore, we also identified signals, including hemiplegic migraine for pirfenidone and asthenia, constipation, as well as flatulence for nintedanib, which were previously unknown or underestimated risks. Conclusion: This study identified AEs and ADRs of pirfenidone and nintedanib in the treatment of IPF, confirming the most of the corresponding label information is relatively safe. However, some unexpected risk signals should be taken seriously, and further research is needed to manage the safety profiles of these drugs in IPF patients.

Objective: Metamizole is quite an old drug with analgesic, antipyretic and spasmolytic properties. Recent findings have shown that it may induce several cytochrome P450 enzymes, especially CYP3A4 and CYP2B6. The clinical relevance of these properties is uncertain. We aimed to unravel potential pharmacokinetic interactions between metamizole and the CYP3A4 substrate quetiapine. Methods: Plasma concentrations of quetiapine from a large therapeutic drug monitoring database were analyzed. Two groups of 33 patients, either receiving quetiapine as a monotherapy (without CYP modulating co-medications) or with concomitantly applied metamizole were compared addressing a potential impact of metamizole on the metabolism of quetiapine being reflected in differences of plasma concentrations of quetiapine and dose-adjusted plasma concentrations (C/D). Results: Patients co-medicated with metamizole showed significantly lower plasma concentrations of quetiapine (median 45.2 ng/mL, Q1=15.5; Q3=90.5 vs. 92.0 ng/mL, Q1=52.3; Q3=203.8, p=0.003). Accordingly, plasma concentrations of quetiapine in the control group were more than twice of those in the metamizole group (+103% higher). The dose-adjusted plasma concentrations were 69 % lower in the co-medication group (p=0.001). Conclusions: The combination of metamizole and quetiapine leads to significantly lower drug concentrations of quetiapine, most likely via an induction of cytochrome P450 CYP3A4 by metamizole. Clinicians have to consider the risk of adverse drug reactions, especially treatment failure under quetiapine when adding metamizole.

This cross-sectional observational study evaluated the availability and switching patterns of branded generics of Vildagliptin, an antidiabetic medication, in a real-world setting. Data from 967 prescriptions obtained from various pharmacies over a 3-month period post-patent expiration were analyzed. The study revealed a diverse range of branded generics, highlighting challenges in consistent availability. Switching patterns were observed, with a significant proportion of patients deviating from the initially prescribed branded generic. These findings emphasize the need for strategies to improve availability and promote appropriate use of branded generics, enhancing cost-effective diabetes management and patient care. Further research is warranted to investigate factors influencing brand switching behaviors and their impact on patient outcomes. This study provides valuable insights for optimizing the prescribing and availability of branded generics, ultimately enhancing the quality of care for patients requiring Vildagliptin treatment.

Background and Purpose: In major depressive disorder (MDD), exploration of biomarkers will be helpful in diagnosing the disorder as well as in choosing a treatment, and predicting the treatment response. Currently, tRNA-derived small ribonucleic acids (tsRNAs) have been established as promising non-invasive biomarker candidates that may enable a more reliable diagnosis or monitoring of various diseases. Herein, we aimed to explore tsRNA expression together with functional activities in MDD development. Experimental Approach: Serum samples were obtained from patients with MDD and healthy controls, and small RNA sequencing (RNA-Seq) was used to profile tsRNA expression. Dysregulated tsRNAs in MDD were validated by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic utility of specific tsRNAs and the expression of these tsRNAs after antidepressant treatment was analyzed. Key Results: In total, 38 tsRNAs were significantly differentially expressed in MDD samples relative to healthy individuals (34 upregulated and 4 downregulated). qRT-PCR was used to validate the expression of six tsRNAs that were upregulated in MDD (tiRNA-1:20-chrM. Ser-GCT, tiRNA-1:33-Gly-GCC-1, tRF-1:22-chrM.Ser-GCT, tRF-1:31-Ala-AGC-4-M6, tRF-1:31-Pro-TGG-2, and tRF-1:32-chrM. Gln-TTG). Interestingly, serum tiRNA-Gly-GCC-001 levels exhibited an area under the ROC curve of 0.844. Moreover, tiRNA-Gly-GCC-001 is predicted to suppress brain-derived neurotrophic factor (BDNF) expression. Furthermore, significant tiRNA-Gly-GCC-001 downregulation was evident following an eight-week treatment course and served as a promising baseline predictor of patient response to antidepressant therapy. Conclusion and Implications: Our current work firstly found that tiRNA-Gly-GCC-001 is a promising MDD biomarker candidate that can predict patient responses to antidepressant therapy.

Background: Assessment of kidney function in emergency settings is essential across all medical subspecialties. Daily assessment of patient creatinine result from emergency medical services showed that some creatinine results apparently deviated from expected creatinine values implying occurrence of drug-related interferences. Methods: Real-time head-to-head clinical evaluation of an enzyme method (Roche CREP2) in comparison to Jaffé gen. 2 method (Roche CREJ2) was performed. During the period of December 2022 and January 2023 we analyzed 8498 patient specimens where 5524 were heavily medicated STAT patient specimens, 500 were pediatric specimens and 2474 specimens were from a distant general population in a different region using the same methods. Results: About 5 percent of hospital specimens having patient history showed apparent drops of creatinine concentrations by the enzyme method against the compensated Jaffé method. Suspect medication was found in 43 out of 46 reviewed patients where medication data were allowed for review. A general patient cohort showed no drops of concentrations measured by the enzyme method. Pediatric hospital cohort showed 6 drops out of 500 total measurements. Conclusions: Pharmacotherapy-induced inaccuracies with enzyme creatinine methods imply the need for proper method validations in the relevant patient population such as emergency hospital setting and may facilitate introduction of cystatin C to emergency medicine clinical practice as suitable creatinine alternate biomarker.

Background: In some breast cancers, decreased estrogen-sulfotransferase (SULT1E1) and its inactivation caused by oxidative-stress lead to elevated E2 levels as well as hypoxia-inducible tissue-damaging factors. Methods: Here, matrix-metalloproteases (MMP2/9) activity and SULT1E1-HIF1α protein/gene expression (Western-blot/RTPCR) were assessed in human breast-cancers versus their adjacent-tissues. Oxidant-stress neutralizer, chalcone (α,β unsaturated ketone) and SULT1E1-inducer dialyl-sulfide (source garlic; Allium sativum) were tested to prevent cancer causing factors in rat, in-vitro and in-vivo model. The antioxidant-enzymres SOD1, catalase, GPx and LDH, and matrix-degenerating MMP2/9 activities were assessed (gel-zymogram). Histoarchitecture (HE-staining) and tissue SULT1E1-localization (immuno-histochemistry) were screened. Extensive statistical-analysis were performed. Results: Human cancer-tissue expresses higher SULT1E1, paralleling HIF1α protein/mRNA owing to lower LDH activity. In addition, increase of MMP2/9 activities commenced tissue damage. However, chalcone and DAS significantly induced SULT1E1 gene/protein, and suppressed HIF1α expression, and MMP2/9 activities in rat tissues. Correlation of individual parameter statistics and group statistics of t-test suggest significant correlation of oxidative-stress (MDA) with SULT1E1 (p=0.006), HIF1α (p=0.006) protein-expression. The NPSH showed a negative correlation (p=0.001) with HIF1α, These two proteins and SULT1E1 mRNA expressions in human breast tumor were significantly higher (p<0.05) compared to the adjacent tissues. Pearson correlation data suggest, SULT1E1 is correlated with NPSH in different exposure groups. Conclusions: Breast cancers associate with SULT1E1, HIF1α and MMPs deregulations. Higher SULT1E1-protein in advanced cancer, remain inactive in oxidant oxidative environment and may be re-activated in chalcone induced reducing-state. Moreover, DAS induced SULT1E1 mRNA expression augments its protein increment. Synergistic drug-effects commenced HIF1α and MMPs suppression. Further studies are necessary.

OBJECTIVES: There is a need for early identification and intervention of Adverse Drug Reaction (ADR) to alleviate unacceptably growing burden, morbidity and mortality associated in People With Epilepsy (PWE). This study is aimed at identifying factors associated with ADR and medication adherence among patients in PWE. METHODS: It is a cross-sectional questionnaire-based study consisting of 940 consenting participants aged 16 years and above attending epilepsy clinics for period of 5years with diagnosis confirmed by International League against Epilepsy (ILAE) criteria and supported by Electroencephalography (EEG). 21-item Liverpool Adverse Effect Profile (LEAP) and 8-item. Morinsky Medication Adherence Scale (MMAS) were used to assess ADR and adherence respectively. RESULTS: The highest reported ADR in PWE were nervousness (34.3%), aggression (33.6%) and weight gain (32.3%). Specifically, (20.1%) of the participant complained of memory problem, while the lowest were hair loss (7.2%), trouble with mouth (8.9%) and problem with skin (9.3%). Using the MMAS, 545(90.2%), 28(4.6%) and 31(5.1%) of PWE in this study were classified as having high, medium, and low adherence, respectively. Duration of AEDs use and duration of epilepsy were the major determinant of ADR in PWE on regression model. CONCLUSION: Duration of AEDs use and duration of epilepsy are the major determinant of ADR in PWE. Effective strategies to identify and reduce ADR should be incorporated to management of PWE by Health Care Providers to improve their quality of life. Furthermore, physician should aim towards reducing the duration of AED use and the epilepsy.

INTRODUCTION: Paroxetine is an antidepressant belonging to the class of SSRI. It is used in multiple psychiatric disorders including depression, anxiety and obsessive-compulsive disorder. Apart from being very efficacious, it causes some adverse effects too and hyponatremia is one of them. The association between the two is not well established, which makes this case worth of attention. CASE PRESENTATION: A 52 years old male hypertensive patient was brought to the ER after having an episode of seizure. Hyponatremia due to an unknown cause was made a provisional diagnosis. He was then referred to the psychiatric department for further assessment, where his detailed history was taken and mental state examination was performed. The patient was found to be suffering from chronic depression. The patient has been taking a combination of antipsychotics and antidepressants for this condition. Paroxetine, Olanzapine and Quetiapine were prescribed to him by his psychiatrist 10 years back, and since then he was taking it daily. His current medication was then immediately altered and paroxetine was replaced by mirtazapine. DISCUSSION/ CONCLUSION: Numerous studies have been done on the effects of SSRIs, but very few of them mentioned their association with hyponatremia. Electrolyte imbalances are common with many medications including antiepileptic and antidepressant drugs as well. Although some literature has shown the link between the two, drug induced hyponatremia remained one of the rarest adverse effect. In summary, paroxetine is very effective in the management of depression but its long-term use could result in an electrolyte imbalance in hypertensive patients

Background: Interleukin-23 (IL-23) inhibitors are widely used in clinical practice for Psoriasis , but multiple adverse events (AEs) have been reported. We aimed to describe the distribution of AEs related IL-23 inhibitors including Guselkumab, Tildrakizumab, Risankizumab, Ustekinumab. Methods: Data from January 1, 2014, to September 30, 2022 were extracted from the FDA Adverse Event Reporting System (FAERS). Disproportionality analysis including reporting odds ratio (ROR) and information component (IC) was performed to access potential signals. It was defined a signal when the lower limit of 95% confidence interval (CI) of ROR (ROR025) more than one or IC(IC025) exceeding zero, with the number of cases greater than or equal to three at the same time. Results: A total of 41,408,408 drug-AE reports were extracted from the FAERS database involving 13271168 people. 704, 13164, 62853, 11399 patients have used Tildrakizumab, Guselkumab, Ustekinumab, Risankizumab and 8, 20, 107 and 115 signals were found respectively. The “infections and infestations” has the highest incidence of SOC in Tildrakizumab(6/8), Guselkumab(5/20), Ustekinumab(50/107), Risankizumab(25/115). Conclusion: Our pharmacovigilance analysis showed that a high frequency was reported for AEs triggered by IL-23 inhibitors. IL-23 inhibitors had the potential to impair immune function resulting in a risk of infections or cancers. We need to pay special attention to Risankizumab because the drug has more AE occurrences than Ustekinumab despite Risankizumab has few reports than Ustekinumab and launched later than Ustekinumab.

Background & purpose Morphine is important for treatment of acute and chronic pain. However, there is high interpatient variability and often inadequate pain relief and adverse effects. To better understand variability in the dose effect relationships of morphine, we investigated the impact of its nonlinear blood-brain-barrier (BBB) transport on mu-opioid receptor (μ-OR) occupancy in different CNS locations, in conjunction with its main metabolites that bind to the same receptor. Methods CNS exposure profiles for morphine, M3G and M6G for clinically relevant dosing regimens based on intravenous, oral immediate- and extended-release formulations were generated using a CNS PBPK model which incorporated nonlinear BBB transport of morphine. The simulated CNS exposure profiles were then used to derive corresponding μ-OR occupancies at multiple CNS pain matrix locations. Results The simulated CNS exposure profiles for morphine, M3G and M6G, associated with nonlinear BBB transport of morphine resulted in varying μ-OR occupancies between the different dose regimens, formulations, and CNS locations. We find that at lower doses, the μ-OR occupancy of morphine was relatively higher than at higher doses of morphine, due to the relative contribution of M3G and M6G. At such higher doses, M6G showed higher occupancy than morphine, whereas M3G occupancy was low throughout the dose ranges. Conclusion and implications Nonlinear BBB transport of morphine influences the μ-OR occupancy ratios of morphine and its metabolites, depending on dose and route of administration, and CNS location. This may impact the clinical effects of morphine treatment for pain relief.

Off-label drug use which could be defined as the practice of prescribing a drug for a different purpose than what is permissible by the regulation is a common practice among clinicians, nevertheless, it is often subject to ethical and legal uncertainties. In general, clinicians must balance the need to provide patients with the best possible care while complying with the regulatory requirements governing drug use. This paper will review the current literature on off-label drug use, including its prevalence, the regulatory landscape, and the ethical issues involved with the aim of formulating an ethical and legal framework that could guide clinicians in using off-label drugs in clinical practice in Malaysia. The framework will include ethical considerations that are centred on the principles of beneficence, non-maleficence, and autonomy, which require clinicians to balance the benefits and risks of using off-label drugs while respecting patients’ autonomy. The legal framework consists of federal and state regulations governing drug use, including the Control of Drugs and Cosmetics Regulations (CDCR) 1984 and other regulations published by the National Pharmaceutical Regulatory Agency (NPRA). The aim of this paper is to provide guidance on how clinicians can navigate the ethical and legal terrain of off-label drug use by understanding the regulatory requirements, being obliged to the requirements of obtaining informed consent from patients and documenting the rationale for off-label use. Ultimately, by understanding the ethical and legal framework, clinicians can provide patients with the best possible care while complying with the regulatory requirements governing drug use.

Anemia is a public health problem affecting about a third of the world's population, the major cause of it being iron deficiency. The many oral iron preparations available at present, are inadequate due to intolerance, or contraindications. IV iron preparations are painful, require patient monitoring and carry the risk of anaphylaxis. Iron salts like Iron pyrophosphate are covered with liposome, a spherical structure of a phospholipidic nature that is similar to those human cell membranes. The bioavailability of liposomal pyrophosphate iron is 3.5 times greater than the free pyrophosphate iron, 2.7 times higher than iron sulfate, and 4.1 times higher compared with iron gluconate. Clinical studies showed that oral liposomal iron is a safe and efficacious alternative to correct anaemia, as also it is a viable treatment option for iron deficiency anaemia in pregnant women.

Abstract Introduction One of the most often used OTC antipyretic and analgesic is paracetamol or acetaminophen. Though widely used, the mechanism by which it reduces fever and pain remains unknown. Although paracetamol is available in a variety of formulations, there are no set guidelines for the various formulations of paracetamol alone or in combination. Materials and Methods In Department of Pharmacology at Government Doon Medical College, the study was planned as an observational cross-sectional study. Data regarding different paracetamol dosages and dosages of paracetamol in fixed dose combinations (FDCs) with various ingredients were gathered and evaluated from the editions of Drug Today, Current Index Of Medical Specialties (CIMS), Monthly Index Of Medical Specialties (MIMS), and India 2021/2022. Results Analysing Drug Today, CIMS and MIMS, it was found, 810 formulations of paracetamol tablets are available in the Indian market, of which, 77 formulations contain only paracetamol, rest being fixed dose combinations (FDCs). Among all the available FDCs with paracetamol having 2or 3 drug formulation, among the 2 constituent FDCs group containing paracetamol, 47% drugs have paracetamol in 325 mg or less dose, whereas, 53% drugs are in clear violation of the notice by CDSCO, by containing more than 325 mg paracetamol. Conclusion In spite of widespread use there is ambiguity in paracetamol doses, as well as absence of data for few constituents in the FDCs. Thus, further research into paracetamol dosing, as well as strict regulation is the need of the hour for one of the most widely used drug.

Abstract: Background: Sotrovimab, a monoclonal antibody, is among the approved therapies for coronavirus disease – 2019 (COVID-19). Sotrovimab binds to the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and inhibits virus attachment to human cells. Real-life experience about the effectiveness of Sotrovimab is limited. We aimed to evaluate the efficacy of Sotrovimab in preventing COVID-19 hospitalizations and other patient-related outcomes as well as the appropriateness of use in an academic hospital in Lebanon. Methodology: In this retrospective observational study, we included adult patients with positive test results for SARS-CoV-2 who received intravenous (IV) Sotrovimab at the American University of Beirut Medical Center (AUBMC) from November 2021 through March 2022. The data collected included patient demographics and comorbidities. Primary outcomes were hospitalization, deterioration after 24 hours, and death due to any cause up to 60 days after the Sotrovimab infusion. Secondary outcomes were progression to critical illness and adverse events. Results: A total of 62 subjects received Sotrovimab infusion at our hospital. More than 50% of the patients had a malignancy. About 77% of the cohort belonged to Tier 1 of the National Institutes of Health (NIH) criteria for Sotrovimab use, and 21% of the patients had clinical deterioration 24 hours after Sotrovimab infusion. The percentage of progression to critical disease was 9.7% and the mortality 6.5 %. Conclusion: Sotrovimab is effective against COVID-19 infection and prevents mortality in high-risk patients.

The dose selections for phase 1 assessments which aim to investigate intrinsic and extrinsic factors of pharmacokinetic variability as well as safety is a central and challenging question in long drug development programs. The dose of an investigational product are selected with respect to regulatory guidances, stage of program, feasibility and maximization of information for later regulatory submission. This review selected 37 development programs of drugs recently approved in the EMA- and FDA-covered regions to explore the doses selected in these trials and also supporting modeling activities with focus on drug interaction, renal and hepatic impairment, food effect and concentration-QTc assessment. This survey found that most sponsors followed regulatory guidance documents, with some interesting deviations. Particular oncology drugs programs but also some cardiovascular programs which have a drug associated safety risks were not able to test supratherapeutic dose levels. Drugs using a titration scheme in development or label were often tested using a dose range. Drugs from combination treatments incorporated the expected exposure increase through interactions or tested the combination in patients. Sponsors included multiple food effect studies due to ongoing formulation developments. Incomplete programs were subject of post market commitments. In this retrospective review, the discrepancies from conventional approaches may give interesting insights into strategic consideration and regulatory acceptability for drug development programs.

Aims: Over the years, Indian regulations have undergone numerous amendments including stringent reporting deadlines, relatedness requirements, and compensation obligations for Serious Adverse Event (SAE). A historic change, New drugs and trial rules- 2019 was proposed on 19th March 2019. Study aimed to ascertain whether various stakeholders were reporting in accordance with the evolving SAE criteria. Methods: Data was retrieved after Ethics approval between August 2014 and December 2021. Data gathered before 19th March 2019, was categorised as “BEFORE” data while remaining data was categorised as “AFTER”. Utilising causality, on-site SAE reporting, and the ethics committee review procedure, we evaluated the compliance. The data was evaluated using descriptive statistics, appropriate statistical tests were used to compare the “BEFORE” and “AFTER” groups. Results: A total of 163 (6.9%) of 2361 studies were drug trials. 26 clinical trials with 77 SAE, 92.3% of which were in Phase-III. Endocrine projects made up 9/26 (34.61%). In the cardiology studies, the greatest SAE distribution was 21 SAEs/ 89 participants (23.59%) with approximately 48% of these being vascular. The “AFTER” group noticed a decrease in the total number and length of SAE sub-committee meetings. In the “AFTER” group, there was significantly higher median number of agenda items/ meetings [8 (4.5 – 10.75)] (p<0.0001). The median interval between the onset of SAE and the first reporting date, however, was just 1 day [IQR: 1-5 days]. In non-death SAEs, there was no significant difference in the compensation paid. Conclusion: There is acceptable adherence to SAE reporting criteria.

Background: Although Two first-generation tropomyosin receptor kinase (TRK) inhibitors larotrectinib and entrectinib have been approved by the Food and Drug Administration (FDA), The current adverse effect profile in the real world remains unknown. Objective: The purpose of this study was to retrospectively examine the adverse effects of two typical first-generation TRK inhibitors by spontaneously mining the data from FDA Adverse Event Reporting System (FAERS) database. Methods: Four general data mining algorithms were used to conduct a disproportionate analysis of TRK inhibitors, and the time of adverse events of drugs was counted. The definition relied on the system organ class (SOC) and preferred terms (PT) by the MedDRA. Results: A total of 326 cases of ‘larotrectinib’ and 450 cases of ‘entrectinib’ as the ‘primary suspect’ drug were collected in this study. A total of 86 adverse drug reaction (ADR) signals involving 18 SOCs were mined. ‘Dizziness’ was the most common ADR, with ‘glioma’ as the strongest signal. The SOC with the highest number of occurrences was ‘Nervous system disorders’.The median time of onset of larotinib and entertinib-related ADR was 41 days and 18 days, respectively. Most cases occurred within one month after treatment. Conclusion: The main ADRs found in this study were ‘Neurotoxicity’, ‘Pain’, ‘Hepatotoxicity’, ‘Drug resistance’, ‘Nephrotoxicity’ and ‘Weight increased’, which provide important support for clinical monitoring and risk identification of TRK inhibitors.

Background: Major Depressive Disorder (MDD) is a heterologous disease in respect to clinical symptoms, severity and responsiveness to treatment, and is often accompanied by somatic comorbidities. The objective of this study was to identify and characterize subgroups of patients with a first-time MDD diagnosis based on somatic drug utilization, including socio-demographic and clinical characteristics, and psychiatric healthcare-related outcomes. Methods: The nationwide register-based study included all Danish patients with an incident MDD diagnosis between 2011 and 2015. Using Latent Class Analysis (LCA), the population was sub-grouped according to somatic drug use (drug profiles). Sociodemographic and clinical characteristics at baseline and odds/hazards of shift in antidepressant treatment and psychiatric hospitalization one year after index were compared between the drug profiles. Trajectories of drug profile membership over time was also analyzed. Results: Of 37,080 MDD patients (mean age 41.5 years, 62% women), the LCA identified five unique somatic drug profiles: 1) limited drug use (74.3%), 2) drugs for pain management (7.6%), 3) cardiovascular drugs (10.7%), 4) drugs for obstructive airway diseases (2.3%) and 5) high drug burden (5.1%). There were large differences in age between the drug profiles, and limited drug use profile and high drug burden profile had lower rates of psychiatric hospitalization than the cardiovascular drug profile. When analyzing the trajectories, we found that the majority of the population continued in the same drug profile during all time intervals. Conclusion: The identified five somatic drug profiles were comparable in respect to the course of the depression during one year following diagnosis.

Paraquat is an extremely corrosive and lethal herbicide. After intentional or unintentional ingestion, paraquat causes extensive mucosal damages extending through the upper gastrointestinal tract which are characterized by pain, inflammation, ulceration, bleeding, and sloughing of the associated mucosa. The aim of this systematic review is to compile and evaluate evidence based studies in relation to the effectiveness of different methods of management of oral mucositis induced by paraquat in terms of reduction of associated pain and duration of symptoms.We undertook computerized electronic searches through both English and Chinese databases so as to identify all published articles in the subject. We also searched reference lists from relevant articles for any related articles. This review is not registered.A total of 10 relevant randomized controlled trials (RCTS) were selected after the electronic searches after satisfying our inclusion criteria. They were published between the 2000s and 2020. The primary outcome measurement assessed an improvement in the healing time/recovery time or adequate pain management. Interventions from all the studies highlighted the use of multi-agent management that included either oral care by the use of bland and multi-agent mouth rinses, corticosteroids, Chinese herbal remedies, growth factors, smectites or anti-oxidant therapy. The main findings were that the main method of management was the implementation of a multi-drug regimen, through the use of compounded preparations or a polydrug system. In addition, herbal and natural remedies, if used appropriately, can play a beneficial role in the management of paraquat induced oral mucositis.

Purpose: To evaluate the drug-induced liver injury (DILI) adverse events related to antidepressants. Method: Post-marketing cases were obtained from the United States Food and Drug Administration Adverse Events Reporting System (FAERS). Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). Result: There were a total of 10,355 reported cases of DILI out of a total of 324,588 cases reported from January 2004 to December 2021. Among the 42 antidepressants assessed, nefazodone (n = 47, ROR = 7.79, IC=2.91), fluvoxamine (n = 29, ROR = 4.69, IC=2.20), and clomipramine (n = 24, ROR = 3.97, IC=1.96), were the top three compounds ranked with the highest reporting odds of cholestatic injury. Mianserin (n = 3, ROR = 21.46, IC=3.99), nefazodone (n = 264, ROR = 18.67, IC=3.84), and maprotiline (n = 15, ROR = 5.65, IC=2.39), were the top three compounds ranked with the highest reporting odds of hepatocellular injury. Nefazodone (n = 187, ROR = 12.71, IC=0.48), clomipramine (n = 35, ROR = 2.07, IC=0.26), and mirtazapine (n = 483, ROR = 1.96, IC=0.94) were the top three on drug related severe hepatic disorders. Only nefazodone detected the signals (n = 48, ROR = 18.64, IC=4.16) in the study of hepatic faliure. Conclusion: The data mining of FAERS suggested significant association between DILI and nefazodone. Duloxetine and clomipramine detected the signals on three categories of DILI besaides hepatic failure. Moreover, DILI risk on the new generation of antidepressants should also be taken into consideration.

We are reporting a case of toxic epidermal necrosis induced by herbal medicine in a 54-year-old woman who had been diagnosed with primary Sjogren’s syndrome for nine years and had discontinued all conventional therapies for at least one year. Approximately two weeks prior to her current admission, she developed crops of petechiae and purpuric macules on her lower extremities, which are typical symptoms of hypergammaglobulinemic purpura of Waldenström, and began taking herbal medicine. The following day, she presented to us with a high fever and new, generalized erythematous rashes over her face and trunk. She was ultimately diagnosed with toxic epidermal necrosis induced by the herbal medicine.

Aims Venous thromboembolism (VTE) is a rare but serious adverse drug reaction could be caused by antipsychotic drugs. However, the specific correlation of VTE caused by antipsychotic drugs is still controversial. This study explored the potential association between antipsychotics and VTE. Method All VTE cases of antipsychotic drugs as primary suspected medicines were extracted from the US Food and Drug Administration adverse event reporting system (FAERS) from 2004 to 2021.Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). Results 4, 455 VTE cases with antipsychotics as primary suspected drugs were identified. The VTE signal was detected in haloperidol, olanzapine, quetiapine and paliperidone. The RORs and the 95% confidence intervals (95% CI) of t haloperidol, olanzapine, quetiapine and paliperidone were (ROR=2.17, 95% CI(2.17-1.91), IC=1.1, 95%CI(1.52-0.66)), (ROR 2.53 95% CI 2.69–2.38 IC 1.31 95%CI 1.52-1.1), (ROR 1.37, 95% CI 1.47–1.28 IC 0.45 95%CI 0.67-0.23) and (ROR 1.6 95% CI 1.83–1.4 IC 0.67 95%CI 1.11-0.22), respectively. Pulmonary embolism occurred in more than 50% of VTE events (2760 cases, 52.84%). The outcome indicated that venous thrombosis caused by antipsychotics is usually a serious consequence. Conclusion The current data mining of FAERS suggested an association between VTE and antipsychotic drugs including olanzapine, haloperidol, paliperidone and quetiapine, which reminds health professionals to pay attention to the serious adverse drug effects of antipsychotic drugs leading to venous thromboembolism.

Aim The prevalence of undocumented medical treatments among children is a significant issue, as well as many EU countries lack access to newly developed children friendly medicines. Consequently, there is a pressing need for supplementary resources that can facilitate informed decision-making regarding children’s medication. We therefore aim to describe the process of establishing a children’s Drug and Therapeutics Committee (cDTC), as well as the preparing and implementation of recommendations for children in the Capital region of Denmark Method Following the guidelines outlined by the World Health Organization a cDTC was established. Recommendations for pediatric medication practice were constructed from assessments of medication use patterns among children in the Capital Region between 2019 and 2021. The recommendations were meticulously crafted based on evaluation of the current marketing authorization landscape and existing best available evidence. Results In 2019, the Capital Region established the first cDTC supported by expert councils and an editorial board. A total of 2.429 purchase item numbers covering 1.222.846 defined daily doses and 592.088 purchased packages covering 10.200.000 defined daily doses were identified in the secondary and primary sectors, respectively. Three comprehensive lists covering recommendations for newborns and children were published between 2021 and 2020 totaling 331 recommended pharmaceutical products. The recommendations primarily intended for use in the secondary healthcare sector were implemented through the revision of 38 pediatric- and 6 neonatal product ranges throughout Capital region. Conclusion Recommendation lists for children governed by a cDTC provide a rational auxiliary tool that can be immediately implemented in the clinic.