Major Adverse Drug Reactions Research Articles

P-2040. Real-world safety and effectiveness of ensitrelvir in COVID-19 patients with risk factor : a post-marketing surveillance in Japan

Abstract Background After obtaining emergency approval on November 22, 2022, a post-marketing surveillance (PMS) in COVID-19 patients was conducted in Japan to investigate the safety and effectiveness of ensitrelvir. We report the safety and effectiveness of ensitrelvir focusing on patients with high-risk (HR) factors for severe COVID-19. Methods In the PMS, COVID-19 patients administered ensitrelvir for the first time in about 500 Japanese hospitals or clinics were targeted and observed for 28 days after the first administration. Patient demographics, concomitant medications, other therapy for COVID-19, adverse events, and clinical course (fever, systemic, respiratory, and gastrointestinal symptoms) were investigated. Results A total of 4155 cases participated from November 2022 to August 2023, and 4125 case reports were collected. The safety and effectiveness analysis population were 3760 and 3638 cases respectively. Among the safety analysis population, the average age was 43.6 years; 452 cases (12.0%) were aged 65 and over; 1823 cases (48.5%) were male; and 939 cases (25.0%) had HR factors. The severity of COVID-19 was mild in 3666 cases (97.5%), moderate 1 in 81 cases (2.2%), moderate 2 in 3 cases (0.1%), and asymptomatic in 10 cases (0.3%). In the safety analysis population, 379 events of non-serious adverse drug reactions (ADRs) were reported, and 5 events (headache, nausea, vomiting, cold sweat, and generalized oedema) of serious ADRs were reported. The major ADRs in the safety analysis population were diarrhoea in 91 cases (2.4%), nausea in 43 cases (1.1%), headache in 42 cases (1.1%), vomiting in 24 cases (0.6%), and rash in 20 cases (0.5%). The frequency of ADRs was 7.09% in the standard-risk (SR) group and 7.56% in the HR group. The median time to resolution of fever was 48.0 hours in the SR group (n=1929) and 36.0 hours in the HR group (n=590). The median time to resolution of all symptoms was 204.0 hours in the SR group (n=2732) and 156.0 hours in the HR group (n=903). Thirteen cases (0.4%) were hospitalized, and the reason was exacerbation of COVID-19 in 10 cases, and others in 5 cases. Conclusion Results of the analysis suggest that ensitrelvir is well tolerated and effective in patients with risk factors same with patients without risk factors. Disclosures Satoru Takashima, n/a, Shionogi & Co., Ltd: Stocks/Bonds (Private Company) Noriko Hayashi, n/a, Shionogi & Co., Ltd: Stocks/Bonds (Private Company) Eri Tsukimura, n/a, Shionogi & Co., Ltd: Stocks/Bonds (Private Company) Eriko Ogura, MD, Shionogi & Co., Ltd: Employee

Increased risk of adverse drug reactions by higher linezolid dose per weight in multidrug-resistant tuberculosis

ObjectivesLinezolid treatment has a high risk of toxicity and adverse drug reactions (ADR) are frequent. Few studies have investigated risk factors of major ADRs separately, therefore, we aimed to evaluate major ADRs including peripheral neuropathy in relation to risk factors and drug concentration levels of linezolid in a high-resource setting for multidrug-resistant tuberculosis (MDR-TB). MethodsWe conducted a retrospective cohort study including participants treated with a linezolid-containing MDR-TB regimen in Sweden 1992–2018. Data was collected from medical records. ADRs were classified according to Common Terminology Criteria for Adverse Events (version 5.0). ResultsOf all participants (n = 132), 43.2% were female and the median age 28 y. The median linezolid treatment was 6.5 months (IQR 3.0–12.7) with a median daily dose of 9.6 mg/kg/d. Any ADR was seen in 58.3% (n = 77) of participants, with 35.6% having peripheral neuropathy (n = 47), 27.3% anaemia (n = 36), 22.0% leukopenia (n = 36) while 6.1% (n = 8) had optic neuritis. The median time for peripheral neuropathy was 3.6 months (IQR 2.1–5.9) and 8.3 months (6.2–10.7) for optic neuritis. A >2.0 mg/L trough concentration (n = 40) was associated with anaemia (P = 0.0038) and thrombocytopenia (P = 0.009) but not with peripheral neuropathy. In multivariable analysis, a dose ≥12 mg/kg/d was associated with time to peripheral neuropathy (HR 2.89, 95% CI 1.08–7.74, P = 0.035), anaemia (HR 6.62, 95% CI 2.22–19.8, P = 0.001) and leukopenia (HR 5.23, 95% CI 1.48–18.5, P = 0.010). ConclusionsLinezolid ADRs were frequent in a high-resource setting. Structured, regular follow-up for ADRs and adjusting dosing according to body weight followed-up by monitoring of drug concentrations early may reduce toxicity.

Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial.

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

Safety and Efficacy of the Ayurvedic Formulation Guduchi Ghana Vati as a Preventive Remedy in COVID-19.

Background and objectives Guduchi (Tinospora cordifolia) is a well-known Ayurvedic herb used as a preventive and curative remedy for various infections and immunity-related conditions. This study aimed to evaluate Guduchi Ghana Vati as a preventive remedy for COVID-19 and non-COVID-19 infections in a healthy population. Materials and methods An open-labeled, multi-centric, randomized, comparative, interventional, prospective community-based clinical study was conducted on healthy individuals at the community level in five different districts of Rajasthan by the National Institute of Ayurveda (NIA), Jaipur, India. Participants were divided into two groups. One group received Guduchi Ghana Vati as an intervention for 45 days, and the control group did not receive any intervention. Incidences of COVID-19 infection, non-COVID-19 infections, their severity, and hospitalization requirements were assessed. Safety was evaluated through monitoring of adverse reactions. Results Among the 10,022 participants who completed the study, the incidence of COVID-19 infection was found to be lower in those taking Guduchi Ghana Vati compared to the control group; however, the difference was statistically non-significant. The severity of COVID-19 based on the WHO ordinal scale was found to be significantly lower in the Guduchi Ghana Vati group compared to the control group. The number of episodes and severity of non-COVID-19 illness were also significantly lower in participants taking Guduchi Ghana Vati compared to the control group. No major adverse drug reactions were observed. Conclusion Guduchi Ghana Vati has the potential to act as a safe and effective remedy for the prevention of infection and immunity-related conditions, including COVID-19.

Time to major adverse drug reactions and its predictors among children on antiretroviral treatment at northwest Amhara selected public hospitals northwest; Ethiopia, 2023.

Adverse drug reaction is one of the emerging challenges in antiretroviral treatment. Determining the incidence rate and predictors among children on antiretroviral treatment (ART) is essential to improve treatment outcomes and minimize harm. And also, evidence regarding the time to major adverse drug reactions and its predictors among children on antiretroviral treatment is limited in Ethiopia. This study aimed to assess the time to major adverse drug reaction and its predictors among children on antiretroviral treatment at selected public hospitals in Northwest Amhara, Ethiopia, 2023. A retrospective cohort study was conducted among 380 children on antiretroviral treatment who enrolled from June 27, 2017, to May 31, 2022. Data was collected using a structured data extraction checklist. Data were entered into Epidata 4.6 and analyzed using STATA 14. The incidence rate of major adverse drug reactions was determined per person/months. The Cox proportional hazards regression model was used to identify predictors of major adverse drug responses. A p-value less than 0.05 with a 95% CI was used to declare statistical significance. The minimum and maximum follow-up time was 6 and 59 months, respectively. The study participants were followed for a total of 9916 person-months. The incidence rate of major adverse drug reactions was 3.5 /1000 person-months. Advanced clinical stages of HIV/AIDS (III and IV) [adjusted hazard ratio = 7.3, 95% CI: 2.74-19.60)], poor treatment adherence [adjusted hazard ratio = 0.33, 95% CI: 0.21-0.42], taking antiretroviral treatment twice and more [adjusted hazard ratio = 3.43, 955 CI: (1.26-9.33)] and not taking opportunistic infection prophylaxis [adjusted hazard ratio = 0.35, 95% CI: 0.23-0.52)] were predictors of major adverse drug reactions. The incidence rate of major adverse drug reactions among children on antiretroviral treatment was congruent with studies in Ethiopia. Advanced clinical stages of HIV/AIDS, poor treatment adherence, taking antiretroviral treatment medications twice or more, and not taking opportunistic infection prophylaxis were predictors of major adverse drug reactions.

Comparison of efficacy between levonorgestrel intrauterine system and dienogest in adenomyosis: a randomized clinical trial.

Medical management of adenomyosis is an emerging perspective in modern gynecology. Though levonorgestrel intrauterine system (LNG-IUS) and dienogest (DNG) effectively relieve symptoms in adenomyosis, neither has been approved for the same indication. Our study aims to compare the efficacy and safety of these progestins in treating adenomyosis. To study the efficacy and safety of LNG-IUS versus DNG in patients with symptomatic adenomyosis. Open-labeled, parallel, single-centered, randomized clinical trial. Patients with adenomyosis-associated pain with or without abnormal uterine bleeding were randomly allocated to either LNG-IUS group or DNG group. The primary outcome was a reduction in painful symptoms after 12 weeks of treatment measured by visual analog scale (VAS) score. Changes in menstrual blood loss (MBL), improvement in quality of life (QoL), and adverse drug reactions were also analyzed. The VAS score significantly decreased from baseline in both groups. The baseline and post-treatment VAS scores in the LNG-IUS group were 6.41 ± 1.07 and 3.41 ± 1.04 (p = <0.001) and in the DNG group, were 6.41 ± 0.95 and 3.12 ± 1.40 (p = <0.001), respectively. A significantly greater proportion of patients in the LNG-IUS group experienced lighter MBL as compared to the DNG group [27/30 (90%) in the LNG-IUS group versus 17/22 (77.2%) in the DNG group (p = 0.006)]. Both the groups had improvement in QOL scores calculated by the World Heath Organisation QOL scale (WHOQOL BREF) questionnaire; however, it was more pronounced in the DNG group [(28.76 ± 30.47 in the LNG-IUS group versus 48.26 ± 44.91 in the DNG group (p = 0.04)]. Both the agents were safe as there were no reported major adverse drug reactions. DNG can be an effective and safe alternative to LNG-IUS for the medical management of adenomyosis. The trial was prospectively registered at the clinical trial registry - India (CTRI) vide CTRI number CTRI/2020/05/025186.

Incidence of side effects of antituberculosis drugs and their related factors in northern Iran: a retrospective cohort study.

Antituberculosis drugs may cause mild, moderate or severe adverse drug reactions (ADR) leading to poor compliance. Description of the pattern of ADR and their related factors can help tuberculosis (TB) control program as part of the WHO programs. This study aims to investigate the incidence of ADR and associated factors among TB patients in northern Iran. This is a retrospective cohort study. The required information, including year of diagnosis, age, gender, residence area, nationality, HIV co-morbidity, history of anti TB treatment and ADR, was obtained from the Deputy of Health, Mazandaran University of Medical Sciences, Iran. All data were analyzed using SPSS version 21 software. Out of 3903 TB patients, 136 (3.5%) experienced major ADR. The incidence of ADR for men and women as well as for those with and without previous treatment history were 3.9% vs. 3.3% and 5.3% vs. 3.4%, respectively (p>0.05). Multiple logistic regression models showed a higher chance of ADR among those aged over 59 compared with those aged under 29 (OR=2.63, 95% confidence interval: 1.54-4.49). Age over 59 can be considered a risk factor for ADR with anti-TB drug administration.

Incidence and Predictors of Major Adverse Drug Reactions Among Human Immunodeficiency Virus–infected Children on Antiretroviral Treatment in West Amhara Comprehensive Specialized Hospitals, Northwest Ethiopia: A Multicenter Retrospective Follow-up Study

Incidence and Predictors of Major Adverse Drug Reactions Among Human Immunodeficiency Virus–infected Children on Antiretroviral Treatment in West Amhara Comprehensive Specialized Hospitals, Northwest Ethiopia: A Multicenter Retrospective Follow-up Study

MetaLAB-HOI: Template standardization of health outcomes enable massive and accurate detection of adverse drug reactions from electronic health records.

This study aimed to advance the MetaLAB algorithm and verify its performance with multicenter data to effectively detect major adverse drug reactions (ADRs), including drug-induced liver injury. Based on MetaLAB, we created an optimal scenario for detecting ADRs by considering demographic and clinical records. MetaLAB-HOI was developed to identify ADR signals using common model-based multicenter electronic health record (EHR) data from the clinical health outcomes of interest (HOI) template and design for drug-exposed and nonexposed groups. In this study, we calculated the odds ratio of 101 drugs for HOI in Konyang University Hospital, Seoul National University Hospital, Chungbuk National University Hospital, and Seoul National University Bundang Hospital. The overlapping drugs in four medical centers are amlodipine, aspirin, bisoprolol, carvedilol, clopidogrel, clozapine, digoxin, diltiazem, methotrexate, and rosuvastatin. We developed MetaLAB-HOI, an algorithm that can detect ADRs more efficiently using EHR. We compared the detection results of four medical centers, with drug-induced liver injuries as representative ADRs. MetaLAB-HOI's strength lies in fully utilizing the patient's clinical information, such as prescription, procedure, and laboratory results, to detect ADR signals. Considering changes in the patient's condition over time, we created an algorithm based on a scenario that accounted for each drug exposure and onset period supervised by specialists for HOI. We determined that when a template capable of detecting ADR based on clinical evidence is developed and manualized, it can be applied in medical centers for new drugs with insufficient data.

Preventing contrast-induced acute kidney injury with probucol and hydration in patients with coronary heart disease: A systematic review and meta-analysis of randomized controlled trials.

Preventing contrast-induced acute kidney injury (CI-AKI) is critical because of its association with poor clinical outcomes, including extended hospital stays and increased mortality. The effects of probucol on preventing CI-AKI have been controversial. Therefore, this systematic review and meta-analysis evaluated the influence of probucol combined with hydration on the CI-AKI risk in patients with coronary heart disease undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). We retrieved data from the following databases from their inception to May 29, 2022: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database (Sinomed), Wanfang Database, and Chinese Scientific Journal Database. The methodological quality of the trials was assessed following the Cochrane Handbook guidelines, and Review Manager 5.3 and Stata 14.0 software were used for the data analysis. We included 14 trials comprising 3306 patients in the analysis. All included trials reported the CI-AKI incidence rate (the primary outcome). Probucol with hydration significantly reduced the CI-AKI incidence compared to hydration alone (odds ratio [OR]: 0.33, 95% confidence interval [CI]: 0.25-0.44, P < .001). Subgroup analyses were performed based on the contrast medium type (iso-osmolality vs low-osmolality contrast medium [LOCM]) and volume (less than or more than 200 mL); the effects of probucol with hydration versus hydration-only on CI-AKI were comparable within each subgroup. Additionally, the serum creatinine (Scr) concentration 24 hours, 48 hours, and 72 hours and the estimated glomerular filtration rate (eGFR) 72 hours after contrast exposure were better in the probucol with hydration group than the hydration-only group. Finally, major clinical adverse events and adverse drug reactions were comparable between the probucol with hydration and hydration-only groups. Probucol with hydration decreases the CI-AKI incidence compared to hydration only in patients with coronary heart disease undergoing CAG or PCI. However, more high-quality, large-sample, multicenter randomized trials are needed to confirm this conclusion.

Adverse drug reactions to first-line antituberculosis drugs at four DOTS centers in Goa, India

BACKGROUND: Major adverse drug reactions (ADRs) can cause significant morbidity and can compromise the treatment regimen. This can result in substantial additional cost due to added outpatient visits to the health facility or laboratory investigations or hospitalization in serious instances. Treatment is often prolonged with additional challenge of compliance. Hence, there is a need to monitor and manage these ADRs timely for better patient care and outcome. This study was carried out with the objective of studying the pattern of ADRs due to first-line antitubercular drugs and to carry out the causality and severity assessment of the reported ADRs.METHODOLOGY: A prospective observational study was conducted at four DOTS centers. All tuberculosis (TB) patients registered and receiving treatment under DOTS were enrolled for the study and were followed up at regular intervals till the end of their treatment. Patients' demographic, personal, disease, investigation, and ADRs details were entered in a predesigned patient recording form. Causality assessment of all ADRs were done using Naranjo algorithm. Severity assessment was done using modified Hartwig and Siegel scale. The study was approved by the institutional ethics committee of the institute. Statistical analysis was conducted using IBM SPSS Statistics for Windows.RESULTS: Of 186 patients, 23 patients (12.26%) developed one or more ADRs. The average number of ADRs per person was 1.43. Majority of the ADRs were reported in the 20–40 years of age group and ADRs were more likely to be among females compared to males. There was no association between type of TB, site of TB, regimen of anti-TB drugs, treatment outcomes, and ADRs. Around 84.85% and 15.15% of ADRs were classified as of mild and moderate severity, respectively, as per modified Hartwig and Siegel scale, while, as per Naranjo algorithm, 72.73% of the ADRs were classified as probable and 27.27% of ADRs as possible. No ADRs were classified as definite.CONCLUSION: Thorough understanding of the various ADRs and their management will help in the effective treatment of TB as well as designing effective counseling methods, which will help in adherence to treatment and also to have better compliance.

The comparison between different over-the-counter drugs Analgesics used to relive cramps pain associated with menstrual cycle for females in Jordan on kidney function

Primary dysmenorrhea is an abdomen cramps caused pain for females under menstrual cycle. The majority of females in Jordan are consuming paracetamol and different types of NSAIDs to relive the mentioned pain. In this study a different group of females between ages 18–24 years old either not consuming any analgesic or consuming paracetamol, ibuprofen, or diclofenac salts have been asked to test the blood creatinine concentration after 10 days of consumption and after 5 and 10 days of discontinuation. SPSS analysis technique was used to analyse the results. As a results, consuming of paracetamol for 10 days show similar creatinine clearance for females without consuming any type of analgesics. While ibuprofen and diclofenac salts show change in kidney function after the 10 days of consumption. Ibuprofen normal kidney function was for 94.1% of the females where only 0.9% of the females show a sign of acute renal failure. On the other hand, the females using diclofenac salts show a high percentage of 61.2% with a sign of acute renal failure. Most of females show restored renal function after discontinuation of analgesics for 5 or 10 days. In conclusion, the consumption of analgesics between females should be monitored while the using of diclofenac salts should be considered as a prescribed drug due to the major and serious adverse drug reactions caused by the daily consumption.

A Comparative Study of Therapeutic Efficacy of BCG Immunotherapy (50 Cases) and Vitamin D (50 Cases) in Cutaneous Warts (Total 100 Cases)

Background: Human papilloma virus infects the epithelium of skin or mucosal cells to cause warts. Most of the current therapeutic modalities are ablative, act only on targeted lesions, and lack a well-defined treatment endpoint. These procedures have high recurrence rates, side effects and are not effective over distant warts. Intralesional immunotherapy acts on cell mediated immunity to treat local as well as distant lesions. Aims and objectives: To evaluate the efficacy and safety of intralesional BCG and intralesional VITAMIN D and to compare efficacy and safety of intralesional BCG and intralesional VITAMIN D in the treatment of patients with cutaneous warts. Materials and Methods: This study included 100 adult patients with single or multiple warts of different size, number and duration with or without distance warts. Each patient was randomly assigned into Group 1 (BCG : 0.1mL of 1mg/mL) and Group 2 (vitamin D3 : 0.2mL of 15mg/mL). One or two warts were injected per session at interval of 21 days for three sessions. Response was assessed. Adverse effects were noted. Cases were further followed up after 3 months without any treatment to assess for any recurrences. In both the groups, standard medical treatment will be also given. Standard digital photographs were taken at each visit to support the data. Results: The BCG group had the maximum patients with complete response (36 of 50, 72%) followed by VITAMIN D group (24 of 50, 48%). No major adverse drug reactions were reported in any of the group. Limitations: Small sample size and absence of control group were the main limitations of our study. Conclusion: Immunotherapy offers a safe, effective and affordable approach in the patients with multiple cutaneous viral warts with lesser side effects and recurrence rate. Keywords: BCG, VITAMIN D, WARTS

TO EVALUATE THE SAFETY AND EFFICACY OF AMLODIPINE AND CHLORTHALIDONE IN COMBINATION WITH TELMISARTAN IN HYPERTENSIVE PATIENTS ATTENDING TERTIARY CARE CENTRE, TELANGANA

Objective: The main objective of this study is to evaluate and compare the effects of both treatments on systolic and diastolic blood pressure in 4th, and 8th weeks with baseline Methods: A prospective, comparative, Open-label, and parallel-group clinical study was conducted in out patient's department of general medicine at Osmania general hospital. 120 patients were randomly allocated into 2 groups. Group 1 with 60 patients received Tab: Telmisartan 40 mg+Amlodipine 5 mg once daily, and Group 2 with 60 patients received Tab: Telmisartan 40 mg+ Chlorthalidone 6.25 mg once daily for a period of 8 w. Follow-up was done in the 4th week and 8th week to evaluate the safety and efficacy in hypertensive patients. Results: The differences in the SBP, DBP, and HR in group A (P value&lt;0.001) and group B (P value&lt;0.001) at the 4th week and 8th week follow-up periods with baseline value (0 w) were statistically significant as P value&lt;0.05. Conclusion: The combination of telmisartan plus amlodipine is equally effective as the combination of telmisartan plus chlorthalidone in decreasing SBP, DBP, HR, and MAP. No major adverse drug reactions were noted during the study period.

Efficacy and Safety of Antiviral Agents in Preventing Allograft Rejection Following CMV Prophylaxis in High-Risk Kidney Transplantation: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Many antiviral agents have been studied in clinical trials for allograft rejection prevention following cytomegalovirus (CMV) prophylaxis in high-risk kidney transplant patients. However, data on the most effective and safest treatment are lacking. We conducted a systematic review and network meta-analysis to rank CMV prophylaxis agents for allograft rejection prevention following CMV prophylaxis in high-risk kidney transplant patients according to their efficacy and safety. We conducted searches on the MEDLINE, Embase, SCOPUS, and CENTRAL databases, as well as the reference lists of selected studies up to December 2021, for published and peer-reviewed randomized controlled trials assessing the efficacy of CMV prophylaxis agents in high-risk kidney transplant patients. Thirteen studies were independently selected by three reviewers and included post-kidney transplant patients indicated for CMV prophylaxis who had been randomized to receive prophylactic antiviral agents or standard of care. The reviewers independently extracted data from the included studies, and direct and network meta-analyses were applied to assess the study outcomes. The probability of efficacy and safety was evaluated, and the drugs were assigned a numerical ranking. We evaluated the risk of bias using the Cochrane Risk of Bias 2.0 tool. The primary outcome was an incidence of biopsy-proven acute rejection, whereas the secondary outcome was a composite of major adverse drug reactions. Each outcome referred to the definition provided in the original studies. Valganciclovir, valacyclovir, and ganciclovir were identified to significantly decrease the incidence of biopsy-proven acute rejection with pooled risk differences (RDs) of −20.53% (95% confidence interval [CI] = −36.09% to −4.98%), −19.3% (95% CI = −32.7% to −5.93%), and −10.4% (95% CI = −19.7% to −0.12%), respectively. The overall major adverse drug reaction was 5.7% without a significant difference when compared with placebo. Valganciclovir had the best combined efficacy and safety among the examined antiviral agents and was the most effective and safest antiviral agent overall for allograft rejection prevention following CMV prophylaxis. Valacyclovir was the optimal alternative antiviral agent for patients who were unable to tolerate intravenous ganciclovir or access oral valganciclovir as financial problem. However, compliance and dose-related toxicities should be closely monitored.

A Score to Predict the Risk of Major Adverse Drug Reactions Among Multi-Drug Resistant Tuberculosis Patients in Southern Ethiopia, 2014-2019.

BackgroundAdverse events (AE) contribute to poor drug adherence and withdrawal, which contribute to a low treatment success rate. AE are commonly reported among multi-drug resistance tuberculosis (MDR-TB) patients in Ethiopia. However, predictors of AE among MDR-TB patients were limited in Ethiopia. Thus, the current study aimed to develop and validate a score to predict the risks of major AE among MDR-TB patients in Southern Ethiopia.MethodsA retrospective follow-up study design was employed among MDR-TB patients from 2014–2019 in southern Ethiopia at selected hospitals. A least absolute shrinkage and selection operator algorithm was used to select the most potent predictors of the outcome. The adverse event risk score was built based on the multivariable logistic regression analysis. Discriminatory power and calibration were checked to evaluate the performance of the model. Bootstrapping method with 100 repetitions was used for internal model validation.ResultsHistory of baseline khat use, long-term drug regimen use, and having coexisting disorders (co-morbidity) were predictors of AEs. The score has a satisfactory discriminatory power (AUC = 0.77, 95% CI: 0.68, 0.82) and a modest calibration (Prob > chi2 = 0.2043). It was found to have the same c-statistics after validation by bootstrapping method of 100 repetitions with replacement.ConclusionA history of baseline khat use, co-morbidity, and long-term drug regimen use are helpful to predict individual risk of major adverse events in MDR-TB patients with a satisfactory degree of accuracy (AUC = 0.77).

Demographic analysis &amp; management strategies for treatment resistant depression

Purpose: A substantial proportion of Major depressive disorder patients do not react properly to antidepressants and are classified as having Treatment Resistant Depression (TRD). This study was undertaken to evaluate the demographic profile and management strategies for TRD in psychiatric department of a tertiary care super-specialty hospital. Methods: In this prospective observational study, a total of 27 subjects diagnosed with TRD were enrolled. Treatment resistant cases in the hospital setting were identified by using Montgomery Asberg Depression Rating Scale (MADRS). We evaluated the demographic profile, major adverse drug reactions and treatment provided for those patients and monitored for improvement of conditions. Results: The demographic profile result shows that females had predominance over males. Furthermore, family history also had a strong correlation with the occurrence of TRD. Sertraline, Venlafaxine and Sodium valproate combination was majorly used in the treatment of TRD patients. Among them, Venlafaxine was used commonly in TRD and the MADRS scores shown improvement in patient condition. Apart from drug therapy ECT when given in combination with antipsychotics were also effective in TRD. The major ADRs shown by TRD patients include weight changes, GI problems and sexual dysfunction.

Machine Learning Models for Predicting Liver Toxicity.

Liver toxicity is a major adverse drug reaction that accounts for drug failure in clinical trials and withdrawal from the market. Therefore, predicting potential liver toxicity at an early stage in drug discovery is crucial to reduce costs and the potential for drug failure. However, current in vivo animal toxicity testing is very expensive and time consuming. As an alternative approach, various machine learning models have been developed to predict potential liver toxicity in humans. This chapter reviews current advances in the development and application of machine learning models for prediction of potential liver toxicity in humans and discusses possible improvements to liver toxicity prediction.

Clinical Outcome and Drug Expenses of Intravitreal Therapy for Diabetic Macular Edema: A Retrospective Study in Sardinia, Italy.

Background: Diabetic macular edema (DME) is a leading cause of visual loss in working-age adults. The purpose of this retrospective study was to perform an epidemiological analysis on DME patients treated with intravitreal drugs in a tertiary hospital. The clinical outcome, adverse drug reactions (ADRs), and intravitreal drug expenses were assessed. Methods: All DME patients treated with Ranibizumab, Aflibercept, Dexamethasone implant, and Fluocinolone Acetonide implant at the Sassari University Hospital, Italy, between January 2017 and June 2020 were included. Central macular thickness (CMT) and best corrected visual acuity (BCVA) were measured. ADRs and drug expenses were analyzed. Results: Two-hundred thirty-one DME patients (mean age: 65 years) received intravitreal agents. Mean CMT and BCVA were 380 μm and 0.5 LogMAR at baseline, 298 μm and 0.44 logMAR after one year (p = 0.04), and 295 μm and 0.4 logMAR at the end of the follow-up period. A total of 1501 intravitreal injections were given; no major ADRs were reported. Treatment cost was €915,000 (€261,429/year). Twenty non-responders to Ranibizumab or Aflibercept were switched to a Dexamethasone implant. In these patients, mean CMT and BCVA were 468 µm and 0.5 LogMar at the time of switching and 362 µm and 0.3 LogMar at the end of the follow-up (p = 0.00014 and p = 0.08, respectively). Conclusion: Results confirm that Ranibizumab, Aflibercept, and Dexamethasone implant are effective and safe in DME treatment. A switch to Dexamethasone implant for patients receiving Aflibercept or Ranibizumab with minimal/no clinical benefit should be considered.

Dual inhibition of COVID-19 spike glycoprotein and main protease 3CLpro by Withanone from Withania somnifera

Dual inhibition of COVID-19 spike glycoprotein and main protease 3CLpro by Withanone from Withania somnifera