Effect of Vortioxetine in Comparison to Fluoxetine on Metabolic Parameters in Patients With Depressive Disorder: A Randomized Controlled Trial.

Background Major depressive disorder (MDD) is a debilitating mood disorder that increases the risk of metabolic syndrome (MS), emphasizing the need for mental and physical health treatments. Although many studies have linked atypical antipsychotics to metabolic disturbances, there is limited evidence linking selective serotonin reuptake inhibitor use to MS. This study aimed to assess the risk of MS among patients with MDD who were administered vortioxetine and fluoxetine. Methodology This was a prospective, open-label, randomized controlled trial conducted in the psychiatry department. Using computer-generated random numbers, the physician assigned fluoxetine 20 mg or vortioxetine 10 mg and recorded MS parameters at baseline and each visit (4, 8, 12, 16, 20, and 24 weeks). This study was registered with CTRI (CTRI/2021/07/034892). Results A total of 122 participants were allocated randomly to the following two groups: group A (n = 60) and group B (n = 62). An independent-sample t-test showed a significant improvement in fasting plasma glucose (FPG) at week eight (p = 0.005), triglycerides (TGs) at week 16 (p = 0.005), high-density lipoprotein (HDL) at week 20 (p = 0.005), and waist circumference at week 24 (p = 0.005) in group A compared to group B. However, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were not significantly associated with either group (p = 0.126 and p = 0.793, respectively). Overall depression remission (Hamilton Depression Rating Scale (HAM-D)) and medication adherence rating scale scores were similar between groups (p = 0.337 and 0.325, respectively). Furthermore, most adverse drug reactions were possibly associated with the study drugs. Conclusions In comparison to group B, group A showed significant improvements in FPG, HDL, and waist circumference more effectively; however, both groups led to higher TG levels, with non-significant numerical improvements observed in SBP and DBP in both groups. In addition, both treatment groups reduced the HAM-D score and had a similar MDD remission rate.

Neurosarcoidosis and Neurologic Complications of Sarcoidosis Treatment.

Sarcoidosis is an immune-mediated multisystem granulomatous disorder. Neurosarcoidosis (NS) accounts for 5% to 35% of cases. The diagnostic evaluation of NS can be a clinical challenge. Gadolinium-enhanced magnetic resonance imaging (MRI) is the gold standard to evaluate central nervous system NS. In almost all cases treatment is warranted. Although glucocorticoids remain the first-line therapy in patients with sarcoidosis, in NS timely initiation of second- or third-line treatment is strongly recommended. Of these, tumor necrosis factor-alpha inhibitors are the most promising. However, the treatment itself may be responsible for/associated with developing neurologic symptoms mimicking NS. Thus, it is important to consider the possibility of drug-induced neurologic symptoms in sarcoidosis.

Controversies regarding lithium-associated weight gain: case-control study of real-world drug safety data.

BACKGROUND: The impact of long-term lithium treatment on weight gain has been a controversial topic with conflicting evidence. We aim to assess reporting of weight gain associated with lithium and other mood stabilizers compared to lamotrigine which is considered free of metabolic adverse drug reactions (ADRs). METHODS: We conducted a case/non-case pharmacovigilance study using data from the AMSP project (German: "Arzneimittelsicherheit in der Psychiatrie"; i.e., Drug Safety in Psychiatry), which collects data on ADRs from patients treated in psychiatric hospitals in Germany, Austria, and Switzerland. We performed a disproportionality analysis of reports of weight gain (> 10% of baseline body weight) calculating reporting odds ratio (ROR). We compared aripiprazole, carbamazepine, lithium, olanzapine, quetiapine, risperidone, and valproate to lamotrigine. Additional analyses related to different mood stabilizers as reference medication were performed. We also assessed sex and age distributions of weight-gain reports. RESULTS: We identified a total of 527 cases of severe drug-induced weight gain representing 7.4% of all severe ADRs. The ROR for lithium was 2.1 (95%CI 0.9-5.1, p > 0.05), which did not reach statistical significance. Statistically significant disproportionate reporting of weight gain was reported for olanzapine (ROR: 11.5, 95%CI 4.7-28.3, p < 0.001), quetiapine (ROR: 3.4, 95%CI 1.3-8.4, p < 0.01), and valproate (ROR: 2.4, 95%CI 1.1-5.0, p = 0.03) compared to lamotrigine. Severe weight gain was more prevalent in non-elderly (< 65 years) than in elderly patients, with an ROR of 7.6 (p < 0.01) in those treated with lithium, and an ROR of 14.7 (p < 0.01) in those not treated with lithium. CONCLUSIONS: Our findings suggest that lithium is associated with more reports of severe weight gain than lamotrigine, although this difference did not reach statistical significance. However, lithium use led to fewer reports of severe weight gain than some alternative drugs for long-term medication (olanzapine, quetiapine, and valproate), which is consistent with recent studies. Monitoring of weight gain and metabolic parameters remains essential with lithium and its alternatives.

Polygenic risk scores in pharmacogenomics: opportunities and challenges-a mini review.

Pharmacogenomics (PGx) aims at tailoring drug therapy by considering patient genetic makeup. While drug dosage guidelines have been extensively based on single gene mutations (single nucleotide polymorphisms) over the last decade, polygenic risk scores (PRS) have emerged in the past years as a promising tool to account for the complex interplay and polygenic nature of patients' genetic predisposition affecting drug response. Even though PRS research has demonstrated convincing evidence in disease risk prediction, the clinical utility and its implementation in daily care has yet to be demonstrated, and pharmacogenomics is no exception; usual endpoints include drug efficacy or toxicity. Here, we review the general pipeline in PRS calculation, and we discuss some of the remaining barriers and challenges that must be undertaken to bring PRS research in PGx closer to patient care. Besides the need in following reporting guidelines and larger PGx patient cohorts, PRS integration will require close collaboration between bioinformatician, treating physicians and genetic consultants to ensure a transparent, generalizable, and trustful implementation of PRS results in real-world medical decisions.

Incidence of adverse drug reactions in COVID-19 hospitalised patients through the minimum basic data set / Incidencia de reacciones adversas a medicamentos en pacientes hospitalizados por COVID-19 a través del conjunto mínimo básico de datos

Background: At the beginning of the COVID-19 pandemic many drugs were used with an uncertain benefit/risk profile that needed to be evaluated. The goal of this study was to analyse the incidence of adverse drug reactions (ADRs) and describe the drugs used in COVID-19 hospitalised patients at the beginning of the COVID-19 pandemic through the minimum basic data set (MBDS). Methods: Retrospective observational study that included hospitalised patients with COVID-19 at our centre between March and May 2020 who had ADRs coded in discharge/death medical reports according to the International Classification of Diseases (ICD-10). Those patients with ADRs ascribed to COVID therapy were selected and the causal relationship was evaluated using the Naranjo algorithm. Descriptive statistical analysis was used. Results: We identified 141 ADRs in 110 cases of hospitalisation due to COVID-19 that entailed an incidence of 9.66% (141/1459), CI95% 8.25-11.29. From the ADRs analysed, 60.3% (85/141) were ascribed to COVID therapy. Lopinavir/ritonavir represented 38.8% (33/85) of ADRs, glucocorticoids 23.5% (20/85) and hydroxychloroquine 9.4% (8/85). Out of the ADRs, 31.8% (27/85) were gastrointestinal disorders (probable lopinavir/ritonavir), 27.0% (23/85) blood glucose disorders (probable glucocorticoid) and 17.6% (15/85) hypertransaminasaemia (probable azithromycin, possible lopinavir/ritonavir, possible hydroxychloroquine, possible interferon). Regarding intensity, 64.7% (55/85) were mild cases, 29.4% (25/85) moderate and 5.9% (5/85) severe. The percentage of ADRs that did not require intervention were 24.7% (21/85), 32.9% (28/85) required pharmacological treatment, 40.0% (34/85) suspension of the drug, 1.2% (1/85) close monitoring and 1.2% (1/85) dose reduction. Conclusions: The incidence of ADR in COVID population that required admission at the beginning of the pandemic seems to be higher than in the general population. The MBDS proves to be a useful tool to trace ADRs. (AU)

Introducción: La llegada de la pandemia de COVID-19 supuso la utilización de muchos fármacos con un perfil de riesgo/beneficio incierto que debe ser evaluado. El objetivo de este estudio fue analizar la incidencia de reacciones adversas a medicamentos (RAM) y describir los medicamentos utilizados en pacientes hospitalizados por COVID-19 al comienzo de la pandemia a través del conjunto mínimo básico de datos (CMBD). Materiales y métodos: Estudio observacional retrospectivo que incluyó pacientes hospitalizados por COVID-19 en nuestro centro entre marzo y mayo de 2020 que presentaban RAM codificadas en los informes médicos de alta/exitus según la Clasificación Internacional de Enfermedades (CIE-10). Se seleccionaron los pacientes con RAM atribuidas a la terapia COVID-19 y se evaluó la relación causal mediante el algoritmo de Naranjo. Se realizó un análisis estadístico descriptivo. Resultados: Identificamos 141 RAM en 110 casos de hospitalización por COVID-19 lo que supone una incidencia del 9,66% (141/1459), IC95% 8,25-11,29. De las RAM analizadas el 60,3% (85/141) se atribuyeron a la terapia COVID. Lopinavir/ritonavir representó el 38,8% (33/85) de las RAM, los glucocorticoides el 23,5% (20/85) y la hidroxicloroquina el 9,4% (8/85). De todas las RAM, el 31,8% (27/85) fueron trastornos gastrointestinales (probable lopinavir /ritonavir), el 27,0% (23/85) trastornos de la glucemia (probable glucocorticoide) y el 17,6% (15/85) hipertransaminasemia (probable azitromicina, posible lopinavir /ritonavir, posible hidroxicloroquina, posible interferón). En cuanto a la intensidad, el 64,7% (55/85) de las RAM fueron casos leves, el 29,4% (25/85) moderados y el 5,9% (5/85) graves. El porcentaje de RAM que no requirió intervención fue 24,7% (21/85), 32,9% (28/85) requirió tratamiento farmacológico, 40,0% (34/85) suspensión del fármaco, 1,2% (1/85) seguimiento estrecho y 1,2% (1/85) reducción de dosis... (AU)

Pharmacovigilance in Herbal Drugs: A Challenge.

There is a growing awareness of a disease at many levels, its treatment, and treatment outcomes including side effects. Alternative therapy techniques, herbal medicines and formulations are extensively acknowledged and practiced in India and around the world. Herbal medicine is usually considered being safe regardless of the absence of scientific evidence to support its claims. Several issues concerning the methods in which herbal medications are labelled, evaluated, sourced, and used are connected to herbal medicine. Herbal therapeutics in the management and treatment of diabetes, rheumatism, hepatic disorders and other mild to chronic diseases and disorders are widely accepted. However, the adversities are difficult to recognize. The idea that the nature is safe and may be taken without the prescription of a physician has resulted in widespread self-medication across the world, sometimes with disappointing results, side effects, or unpleasant after-effects. The existing pharmacovigilance paradigm and its accompanying tools were created in connection with synthetic medicines. Nevertheless, adopting these approaches to keep records of herbal medications' safety poses a distinct challenge. This might be due to the variations in the usage of non-traditional medicines, which can offer unique toxicological issues whether taken alone or in conjunction with other medications. The goal of pharmacovigilance is to identify, analyse, explain, and minimize the adverse reactions and other drug-related complications associated with herbal, traditional, and complementary medications. Systematic pharmacovigilance is required to collect accurate data on the safety of herbal medications to create adequate guidelines for effective and safe usage.

Development of Pharmacovigilance System in India and Paradigm of Pharmacovigilance Research: An Overview.

The drugs are projected to cure, prevent and treat diseases; however, there are also chances of mild or severe adverse drug reactions (ADRs) in the patients. Pharmacovigilance (PV) enhances the approach to safe medicines and healthcare, but integration into public healthcare remains a challenge in many countries. The Pharmacovigilance Programme of India (PvPI) is a nationwide programme launched by the Ministry of Health and Family Welfare (MoHFW), Government of India, on 14 July 2010. It is currently run by the Indian Pharmacopoeia Commission (IPC). Presently, 567 ADR Monitoring Centres (AMC) are functioning under PvPI across India. The Central Drugs Standard Control Organization (CDSCO), under the Directorate General of Health Services (DGHS), and the Ministry of Health, Family & Welfare (MoHFW) Government of India is the National Regulatory Authority (NRA) of India. This review aims to trace the development of PV in India and its status among the top ADR reporting countries, with a focus on the current status of the studied ADR in different regions in India. Among the top 20 countries enthusiastic about sending ICSR per million population between 2015 and 2020, India shares 2% of the total ICSRs in VigiBase. India is now being recognized as a hub of global clinical trials and clinical research studies. Hence, it is the need of the hour in India to have a dynamic PV network system with an efficient and prudent operation method. Nevertheless, in India, PV programs are at an early stage on par with other countries, and only because of underreporting of ADRs. However, in the future, PvPI may appear as a big dashboard for ADR reporting culture in India as it continuously works hard to improve patients and drug safety.

Artificial Intelligence in Pharmacovigilance and COVID-19.

The history of pharmacovigilance started back 169 years ago with the death of a 15- year-old girl, Hannah greener. However, the Thalidomide incident of 1961 brought a sharp change in the pharmacovigilance process, with adverse drug reaction reporting being systematic, spontaneous, and regulated timely. Therefore, continuous monitoring of marketed drugs was essential to ensure the safety of public health. Any observed adverse drug reaction detected by signals was to be reported by the health profession. Moreover, signal detection became the primary goal of pharmacovigilance based on reported cases. Among various methods used for signal detection, the Spontaneous Reporting System was most widely preferred; although, it had the limitation of "under- reporting". Gradually, the World Health Organization collaborating centre and "Uppsala Monitoring Centre" were established in 1978 for international monitoring of drugs. The centre was responsible for operating various databases like vigiflow, vigibase, vigilyze, and vigiaccess. Recently, huge data could be generated through spontaneous reporting linked with computational methods, such as Bayesian Framework, E-Synthesis. Furthermore, drug safety surveillance at an early stage prior to the official alerts or regulatory changes was made possible through social media. In addition, India created a National Pharmacovigilance Program, and Schedule Y of the Drug and Cosmetic Act 1945 was reviewed and amended in 2005. The collaboration of Information Technology and Pharmaceutical Company can further enhance the awareness regarding artificial intelligence in pharmacovigilance, which was in its infancy until 2017. Artificial intelligence helps improve the quality and accuracy of information much quickly.

Unraveling Catechol-O-Methyltransferase rs4680 SNP's Role in Patients' Response to Tramadol and Its Adverse Effects: A Pharmacogenetics Insight into Postoperative Pain Management.

Effective postoperative pain management is essential for patient well-being and an efficient healthcare system. Variations in the Catechol O-Methyltransferase (COMT) gene, specifically rs4680, play a crucial role in pain perception and opioid response. This study seeks to elucidate the impact of rs4680 polymorphism on tramadol efficacy and adverse reactions in post-surgical patients. We performed an uncontrolled cohort pharmacogenetics study in which participants underwent postoperative tramadol administration. The frequencies of rs4680 alleles were determined and the association between rs4680 genotypes and the efficacy of tramadol analgesic as pain relief, measured by the Numeric Rating Scale (NRS), was analyzed. Secondary outcomes included tramadol-induced sedation levels, opioid-induced nausea and vomiting, and other adverse effects of tramadol. Data analysis, using IBM SPSS Statistics 23, focused on pain and side effect differences across genotypes, with statistical significance set to p ≤ 0.05. The COMT (rs4680) genotype distribution exhibited a 'G' allele frequency of 41.5% and an 'A' allele frequency of 58.5%, with the AA genotype present in 44% of individuals, adhering to the Hardy-Weinberg equilibrium (p = 0.788). Patients with the AA genotype reported lower pain scores post-tramadol administration across all times examined (p < 0.001), but also experienced statistically significant (p < 0.001) higher incidences of tramadol-induced nausea, vomiting, and sedation. However, GG genotype individuals experienced poor pain relief from tramadol, requiring more supplemental analgesia. These significant findings underscore the critical role of COMT rs4680 polymorphism in response to tramadol and the necessity of a personalized approach to postoperative pain management.

Class-imbalance Prediction and High-dimensional Risk Factor Identification of Adverse Reactions of Traditional Chinese Medicine with Centralized Monitoring in Real-world Hospitals / 中国实验方剂学杂志

ObjectiveTo achieve high-dimensional prediction of class imbalanced of adverse drug reaction（ADR） of traditional Chinese medicine（TCM） and to classify and identify risk factors affecting the occurrence of ADR based on the post-marketing safety data of TCM monitored centrally in real world hospitals. MethodThe ensemble clustering resampling combined with regularized Group Lasso regression was used to perform high-dimensional balancing of ADR class-imbalanced data， and then to integrate the balanced datasets to achieve ADR prediction and the risk factor identification by category. ResultA practical example study of the proposed method on a monitoring data of TCM injection performed that the accuracy of the ADR prediction， the prediction sensitivity， the prediction specificity and the area under receiver operating characteristic curve（AUC） were all above 0.8 on the test set. Meanwhile， 40 risk factors affecting the occurrence of ADR were screened out from total 600 high-dimensional variables. And the effect of risk factors on the occurrence of ADR was identified by classification weighting. The important risk factors were classified as follows：past history， medication information， name of combined drugs， disease status， number of combined drugs and personal data. ConclusionIn the real world data of rare ADR with a large amount of clinical variables， this paper realized accurate ADR prediction on high-dimensional and class imbalanced condition， and classified and identified the key risk factors and their clinical significance of categories， so as to provide risk early warning for clinical rational drug use and combined drug use， as well as scientific basis for reevaluation of safety of post-marketing TCM.

Individual Pharmacotherapy Management (IPM)-IV: Optimized Usage of Approved Antimicrobials Addressing Under-Recognized Adverse Drug Reactions and Drug-Drug Interactions in Polypharmacy.

Antimicrobial therapy is often a life-saving medical intervention for inpatients and outpatients. Almost all medical disciplines are involved in this therapeutic procedure. Knowledge of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) is important to avoid drug-related harm. Within the broad spectrum of antibiotic and antifungal therapy, most typical ADRs are known to physicians. The aim of this study was to evaluate relevant pharmacological aspects with which we are not so familiar and to provide further practical guidance. Individual pharmacotherapy management (IPM) as a synopsis of internal medicine and clinical pharmacology based on the entirety of the digital patient information with reference to drug information, guidelines, and literature research has been continuously performed for over 8 years in interdisciplinary intensive care and trauma and transplant patients. Findings from over 52,000 detailed medication analyses highlight critical ADRs and DDIs, especially in these vulnerable patients with polypharmacy. We present the most relevant ADRs and DDIs in antibiotic and antifungal pharmacology, which are less frequently considered in relation to neurologic, hemostaseologic, hematologic, endocrinologic, and cardiac complexities. Constant awareness and preventive strategies help avoid life-threatening manifestations of these inherent risks and ensure patient and drug safety in antimicrobial therapy.

Utility of Lymphocyte Transformation Test for Assisting Updated Roussel Uclaf Causality Assessment Method in Drug-Induced Liver Injury: A Case-Control Study.

Background: The Roussel Uclaf Causality Assessment Method (RUCAM) is a validated tool for assessing causality in cases of suspected drug-induced liver injury (DILI). However, RUCAM cannot discriminate between concomitant hepatotoxic drugs with the same temporal sequence. Objective: To analyse the utility of the lymphocyte transformation test (LTT) for assisting updated RUCAM in 45 patients and 40 controls with a clinical diagnosis of DILI. Methods: Suspected DILI cases were detected through the Prospective Pharmacovigilance Program from Laboratory Signals in Hospital (PPLSH) or by consultations. The controls completed the drug therapy with no adverse reactions during the study period. A receiver operating characteristics (ROC) curve analysis was performed to calculate the optimal cut-off value for the stimulation index (SI), corresponding to the largest sum for the specificity and sensitivity values of LTT for true DILI cases. Results: Out of 45 patients diagnosed with DILI, 42 cases were detected by the PPLSH, two cases by consultation and one case by both methods. Most DILI cases (64.4%) arose during hospitalization. According to the biochemical parameters, 24 cases (53.3%) had the hepatocellular phenotype, 14 (31.1%) had the cholestatic phenotype, and 7 cases (15.6%) had the mixed phenotype. Considering the severity criteria, 7 (15.5%) cases were classified as moderate DILI, and 4 (8.9%) were severe DILI; there were no fatal cases. A total of 149 drugs (median/case, 3; IQR, 2-5) were suspected to be involved in the DILI cases (RUCAM score ≥3). In 8 cases, only one drug was suspected, and polypharmacy (≥5 drugs) was identified in 29% of the cases. Of all DILI cases, 46 (30.9%) of the 149 suspected drugs produced positive LTT results, and the LTT was positive in 34 (75.5%) of the 45 patients. No exposed controls produced positive LTT results. The optimal cut-off of 1.95 for the SI was obtained with a sensitivity of 77% and specificity of 100% (area under the curve, 0.91; 95% asymptotic confidence interval 0.84-0.97; p < 0.001). The sensitivity of the hepatocellular phenotype was 92%. Conclusion: Our results demonstrate that LTT is an add on strengthening causality in cases of suspected idiosyncratic DILI, especially for patients with several suspected drugs and a hepatocellular phenotype.

Nutritional evaluation study based on NRS 2002, OPNI, and their combined use in patients with adverse drug reactions after chemotherapy: a cross-sectional study.

Background: It is important to assess the nutritional status of patients who have experienced adverse drug reactions (ADRs) after chemotherapy. We aimed to explore the nutritional status of patients who developed ADRs after chemotherapy, using the Nutritional Risk Screening 2002 (NRS 2002) tool, the Onodera Prognostic Nutrition Index (OPNI), and their combined application. Methods: NRS 2002 screening and OPNI calculation for patients before chemotherapy. Patients with ADRs after chemotherapy were grouped according to the NRS 2002, OPNI, and combined scores from both assessments. The types of ADRs were classified according to the National adverse drug reaction monitoring system (http://www.adrs.org.cn/). The impact of nutritional risk on the classification and types of ADRs in cancer chemotherapy patients was analyzed. Logistic regression was used to analyze the key influencing factors of gastrointestinal damage and bone marrow suppression. the consistency between the NRS 2002, OPNI, and their combined application analyzed. Results: The difference in body mass index (BMI) scores between the OPNI (P=0.041) and NRS 2002 groups was statistically significant (P=0.051). The difference in ADR type in the OPNI subgroups (P=0.04) was statistically significant. It showed that the proportion of new and severe ADRs in the low OPNI group (47.14%) was significantly higher than that in the high OPNI group (27.13%). The differences in digestive tract-associated ADRs were statistically significant among the OPNI groups (P=0.004), NRS 2002 groups (P=0.012), and combined measures groups (P=0.000), as were the differences in myelosuppressive-type ADRs in the OPNI groups (P=0.035), NRS 2002 groups (P=0.000), and combined measures groups (P=0.000). Logistic regression analysis showed that BMI was the key influencing factor for digestive tract-associated ADRs (95% CI: 1.267, 95% CI: 1.022-1.570, P=0.031) and myelosuppressive-type ADRs (95% CI: 1.213, 95% CI: 1.020-1.443, P=0.029). It had good consistency with the combined measures of nutritional risk (Kappa value =0.675). Conclusions: Patients with severe ADRs after chemotherapy showed low OPNI values, high NRS 2002 scores, and malnutrition. These patients also had a significantly increased incidence of digestive tract and myelosuppressive-type ADRs with BMI as the key influencing factor. The combined assessments showed good consistency with the NRS 2002 scores.

Detection and Prevention of Medication Errors by the Network of Sentinel Pharmacies in a Southern European Region.

A medication error (ME) is a drug-related problem that has been recognized as a common and serious threat to patient safety. The aim of this study was to detect and analyze ME reports occurring throughout the therapeutic process through the community's pharmacies in order to improve the efficacy and safety of medications and contribute to the prevention of future MEs. This was a three-year descriptive, observational, and prospective study to detect and analyze the different MEs reported by the Catalan sentinel pharmacies network (Catalan SePhaNet). In total, 1394 notifications of MEs were reported (an incidence rate of 737.34 cases/100,000 inhabitants). MEs were detected more frequently in primary care centers. Most of the MEs reported were caused by an incorrect, incomplete, illegible, or verbal medical prescription (41.3%). Of the global notifications detected, 71.9% did not reach the patient (categories A and B). The drugs most frequently implicated in the reported ME cases were beta-lactam antibiotics. In 6.0% of the cases, the ME caused injury to the patient (categories E and F). In 72.0% of the global notifications, a pharmacist's intervention avoided the ME. The importance of a community pharmacy and the role of a pharmacist were demonstrated in aspects related to patient and drug safety.

Efficacy and safety of alectinib in ALK-positive non-small cell lung cancer and blood markers for prognosis and efficacy: a retrospective cohort study.

Background: Alectinib is a second generation of ALK-tyrosine kinase inhibitors (ALK-TKIs), which has attracted much attention in the treatment of ALK-positive non-small cell lung cancer (NSCLC). At present, there are few reports on the efficacy and safety of alectinib in Chinese population. Moreover, biomarkers reflecting prognosis and efficacy are exceedingly needed. This study assessed the efficacy of alectinib in patients with ALK-positive NSCLC and analyzed the prognostic factors. Methods: Patients with ALK-positive NSCLC who were confirmed by histopathology or cytology at the Affiliated Cancer Hospital of Nanjing Medical University between October 2018 and October 2021 were enrolled. All patients were treated with alectinib. The clinical characteristics and circulating tumor biomarkers before and after treatment were collected. Kaplan-Meier test was used to calculate the progression-free survival (PFS). Univariate and multivariate Cox regression analyses were used to explore the influencing factors on PFS. Incidence of adverse events was observed. Results: Twenty patients progressed after first-line treatment (n=59) with alectinib, and 21 patients progressed following second-line treatment (n=36) with alectinib. The median PFS of first-line treatment patients was not achieved, and the median PFS of patients undergoing second-line treatment was 15.0 months [95% confidence interval (CI): 0.00-32.23]. The most common adverse reactions were liver dysfunction (37.50%), anemia (37.50%), and constipation (20.83%). The incidence of grade III and above adverse reactions was 6.25%. Univariate analysis showed that neutrophil-to-lymphocyte ratio [NLR; hazard ratio (HR) =0.424, P=0.005] carcinoembryonic antigen (CEA; HR =0.482, P=0.029), lactate dehydrogenase (LDH; HR =0.327, P<0.001), carbohydrate antigen (CA)199 (HR =0.313, P=0.002), and circulating cell free DNA (cfDNA; HR =0.229, P=0.008) concentration levels were associated with PFS, and multivariate analysis showed that NLR (HR =3.058, P=0.034) was independent prognostic factor. After three months of treatment, CEA, CA199, NLR, and LDH, could further predict the prognosis of alectinib treatment. Conclusions: The efficacy and safety of alectinib as a first-line or second-line treatment for ALK-positive NSCLC in keeping with published prospective studies. CEA, CA199, NLR, and LDH within the normal range after three months of treatment were associated with good prognosis. Detection of serum tumor markers can indicate therapeutic success in patients treated with alectinib.

"Is medical cannabis safe for my patients?" A practical review of cannabis safety considerations.

Medical cannabis use is increasing worldwide. Clinicians are commonly asked by patients to provide guidance on its safety and efficacy. Although there has been an increase in research on the role of medical cannabis for a number of different conditions, we found that there was a paucity of clear safety guidance on its use. We aim to address this issue by answering two pertinent clinician safety questions: 1 Can medical cannabis be safely used in this patient? 2. What strategies can be used to ensure that any harms from medical cannabis are mitigated? To address these questions, we reviewed available evidence and provided expert clinical opinion to summarize the fundamental components for evaluating medical cannabis safety and strategies to reduce risk from its use. Our review resulted in a safety-focused framework for medical cannabis initiation and utilization. We provide clear recommendations for patients being considered for cannabis (e.g. precautions, contraindications and drug interactions). Risk mitigation strategies such as appropriate chemovar (strain) selection, routes of administration, and dosing are reviewed. As with any other pharmacotherapy, we review the key components of monitoring and address potential issues that may arise while using medical cannabis. We propose a structured assessment and monitoring strategy that can be used by clinicians recommending cannabis (CRC) to guide patients through each step of their cannabis journey. This framework can be used to ensure that medical cannabis utilization is associated with the lowest possible risk to the patient.

Trends of Adverse Drug Reaction Reports in a Hospitalized Psychiatric Population: Exploring Prescriber Discontinuations as Potential Unreported Adverse Drug Events.

The review of adverse drug reactions (ADRs) is a safety mandate required by numerous organizations in the medication safety community. For adverse reactions to be properly reviewed, they must first be reported as potential events. There are notable challenges to ensure adequate and accurate reporting of ADRs that could be overcome if obstacles were better understood and addressed in a manner that is not punitive or threatening. Even reports of seemingly benign side effects might be valuable when considering the deleterious impact on medication adherence, notably in a psychiatric population. Our study examines the potential underreporting of adverse drug reactions that have been likely dismissed as expected side effects of medications. We underscore that there is a significant difference in what has been reported formally as an ADR and what should be reported based on the ability to identify prescribing changes that might be initiated in response to an ADR.

Analysis of severity and preventability in patients of-Toxic epidermal necrolysis-A case series.

SJS-TEN is life-threatening autoimmune disorder triggered due to drugs such as analgesics, antibiotics, anticonvulsants, and antipsychotics. This report provides awareness to the Clinicians regarding prescription of drugs which cause SJS-TEN. Among young females of 20-40 years, screening for previous history, issuing drug alert cards, and preventing OTC prescriptions decreases mortality.