Incidence Of Adverse Drug Reactions Research Articles

Preliminary efficacy and safety of YSCH-01 in patients with advanced solid tumors: an investigator-initiated trial

ObjectiveTo evaluate the safety and preliminary efficacy of YSCH-01 (Recombinant L-IFN adenovirus) in subjects with advanced solid tumors.MethodsIn this single-center, open-label, investigator-initiated trial of YSCH-01, 14 patients with advanced solid...

Pharmacogenomics as a Tool in Addressing Genetic VariationDependent Adverse Drug Reactions

Adverse drug reactions (ADRs) are a cause of discontinuing drug development and withdrawal from market, as well as a very common  source of morbidity and mortality. Genetic variables may be the primary predictor of drug response for certain medications, but they are  estimated to account for 15– 30% of the variability in drug response. Many factors can contribute to adverse drug reactions, including  genetics and drug targeting/delivery. Genetic markers, such as single nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes,  drug targets, and human leukocyte antigen (HLA) genotypes, have been associated with an increased risk of ADRs. Pharmacogenomics is  the study of the genetic variation in the way that different people react to different pharmaceuticals, including variations in the risk of  adverse drug reactions, dose requirements, and efficacy. The implementation of genetic data for predicting responses to medications  and ADRs is becoming a reality in clinical practice, offering the potential to reduce the incidence of ADRs and improve patient outcomes.  As pharmacogenomic research continues to advance, it holds great promise for enhancing drug safety and efficacy, ultimately leading to  more tailored and effective therapeutic interventions. 

Safety and effectiveness of clofarabine in Japanese patients with relapsed/refractory acute lymphoblastic leukaemia: a post-marketing surveillance study.

Clofarabine is used to treat acute lymphoblastic leukaemia, but evidence of its safety and effectiveness in Japanese patients is limited. We evaluated the safety and effectiveness of clofarabine in patients with relapsed/refractory acute lymphoblastic leukaemia in real-world clinical practice in Japan. An observational, multicenter, post-marketing, all-case surveillance was conducted for safety. Effectiveness analyses were conducted in patients aged ≤21years and those treated with clofarabine monotherapy and combination therapy (clofarabine plus etoposide and cyclophosphamide). In the all-case survey, 260 of 264 registered patients were eligible for safety analysis. Among the 225 patients eligible for effectiveness analysis, 139 were aged ≤21years. For monotherapy and combination therapy, 20/31 and 34/88 patients were eligible, respectively. In the all-case survey, the median age was 16.0years, and 47.7% of patients were<15years old. Adverse drug reaction incidence was 83.5% and the most common were hematologic toxicities. The best overall response rates in the population aged ≤21years were complete remission, 29.7%; complete remission without platelet recovery, 7.3% and partial remission, 10.9%. The rest (52.2%) were classified as ineffective. The sum of complete remission, complete remission without platelet recovery and partial remission rates (effectiveness rate) was 47.8% (66/138 patients). The effectiveness rates in the monotherapy and combination therapy surveys were 10.0% (2/20 patients) and 58.8% (20/34 patients), respectively. These post-marketing surveys provide real-world evidence of the safety and effectiveness of clofarabine regimens, including monotherapy and combination therapy in Japanese patients with relapsed/refractory acute lymphoblastic leukaemia. The safety and effectiveness profiles were comparable with those of previous prospective studies.

Study on the clinical efficacy and safety of baloxavir marboxil tablets in the treatment of influenza A.

To evaluate the clinical efficacy and safety of baloxavir marboxil tablets in the treatment of influenza A. According to a random sequence generated by computer software, 200 patients with confirmed influenza A were divided into a study group and a control group with 100 cases in each group. Group allocation was concealed using sealed envelopes. The study group was treated with oral administration of baloxavir marboxil tablets, 40 mg once. The control group was given oral oseltamivir capsules, 75 mg twice a day, for five consecutive days. The therapeutic effects, symptom disappearance time and adverse drug reactions of the two groups after 5 days of treatment were compared. There was no significant difference in the total effective rate between the two groups (99% vs. 98%, p > 0.05). There was no significant difference in fever subsidence time (1.54 ± 0.66 d vs. 1.67 ± 0.71 d, p > 0.05), cough improvement time (2.26 ± 0.91 d vs. 2.30 ± 0.90 d, p > 0.05) and sore throat improvement time (2.06 ± 0.86 d vs. 2.09 ± 0.83 d, p > 0.05) between the two groups. There was no significant difference in the incidence of adverse drug reactions between the two groups (8% vs. 13%, p > 0.05). Baloxavir marboxil tablets can be effectively used in the treatment of patients with influenza A and have a similar efficacy and safety profile as oseltamivir capsules.

Análisis de Reacciones Adversas a Medicamentos por fármacos antipsicóticos en un instituto de salud mexicano

Introduction: Adverse Drug Reactions (ADR) are unwanted clinical or laboratory manifestations that are related to drug use. ADR are common and are associated with significant risk of morbidity, mortality and hospital admissions. Antipsychotics have a reduced therapeutic window, and have been related to the manifestation of a variety of ADR. Objective: To evaluate the pattern of ADRs due to antipsychotic drugs detected in patients treated at the Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz between December 2021 and May 2022. Methods: Observational, descriptive, prospective and cross-sectional study of a series of cases. The seriousness, severity, and quality of the information in the notification of the ADR were defined in accordance with NOM-220-SSA1-2016, Installation and Operation of Pharmacovigilance, while causality was determined using the Naranjo algorithm. Results: The incidence of ADRs was 59%, with one or more ADR detected in 52 of the 88 patients who were receiving antipsychotic treatment during the study period. Forty-five percent of the ADR had probable causality and 55% possible; only three ADR were classified as serious as they prolonged the hospital stay and endangered the patient's life. Conclusions: The ADR of the gastrointestinal and endocrine systems were the most incidental, with hyperprolactinemia being the most frequent. Olanzapine and clozapine were the medications that caused the most ADR. It is recommended to promote the culture of notification and follow-up of ADR caused by antipsychotic drugs.

Predictive Pharmacogenetic Testing in Psychiatry: Pros and Cons

Pharmacogenetic testing (PGx) is an important diagnostic tool for achieving an optimal balance between the effectiveness and safety of psychotropic drugs, especially those requiring long-term use. The most prescribed medications in psychiatric practice are antipsychotics (APs). Despite the long period of use of APs, their safety profile remains insufficiently high. Due to the high incidence of adverse drug reactions (ADRs), from the central nervous system (CNS) and other organs and tissues of the human body. Therapeutic drug monitoring can help predict and diagnose AP-induced ADRs only if the patient is receiving APs. PGx helps to individually select an AP, its dose and clarify the risk of ADRs before prescribing an AP, or at the start of therapy. This explains the importance of PGx in psychiatrist practice. However, to date, most practicing psychiatrists rarely use predictive PGx or do not use this method. PGx is more often prescribed in the case of a long history of un-successful AP-therapy, or in the case of the development of serious ADRs, the risk of which could be significantly reduced if predictive PGx was used. This case report of PGx in a 56-year-old woman with severe bipolar disorder demonstrates that the trajectory of ADRs and socialization could be significantly improved if this method was prescribed before the initiation of APs, rather than in the event of the development of serious ADRs.

Safety of non-ionic contrast media in CT examinations for out-patients: retrospective multicenter analysis of 473,482 patients.

This study aimed to explore the incidence of and potential risk factors for adverse drug reactions (ADRs) after non-ionic iodinated contrast media (NICM) administration for CT exams in out-patient settings in China. A total of 473,482 out-patients who underwent intravenous NICM between January 1st, 2017, and Dec 31st, 2021, were retrospectively enrolled from three institutions. The occurrence of ADRs and clinical information were recorded. Chi-square test, Poisson regression, and logistic regression analyses were used to evaluate potential ADR risk factors and correlation with demographics, season, and NICM type. Among the 473,482 patients (mean age 55.22 ± 14.85; 253,499 male) who received intravenous NICM, the overall ADR incidence was 0.110% (522 of 473,482), with 0.099% acute-related drug reactions (469 of 473,482) and 0.0004% serious ADRs (two of 473,482). Iopromide was associated with a higher risk of acute ADRs. Late ADRs were more frequently observed with iodixanol 320. Multi-level logistic regression of patients with acute ADRs and a control group (matched 1:1 for age, gender, NICM, prescriber department, and institution) showed that summer (adjusted OR = 1.579; p = 0.035) and autumn (adjusted OR = 1.925; p < 0.001) were risk factors of acute ADRs. However, underlying disease and scanned body area were not related to a higher ADR incidence. The use of NICM for out-patients is in general safe with a low ADR incidence. The type of contrast medium (iopromide) and the seasons (summer and autumn) were associated with a higher risk of acute ADRs. Late ADRs were more often observed with iodixanol. In comparison to in-patients, out-patients may be exposed to higher risk due to a lack of extensive risk screening, less nursing care, and higher throughput pressure. Safety data about NICM from a large population may complement guidelines and avoid ambiguity. • The incidence and risk factors for adverse events after using non-ionic iodinated contrast media are complex in out-patients. • Non-ionic iodinated contrast media are safe for out-patients and the overall incidence of adverse drug reactions was 0.110%. • There is a higher risk of acute adverse drug reactions in summer and autumn.

Post-marketing surveillance of zinc acetate dihydrate for hypozincemia in Japan.

Zinc is an essential microelement, and its deficit causes various diseases and symptoms. In adults, especially in elderly individuals, zinc shortage can cause symptoms such as taste disorder, dermatitis, and susceptibility to infection. In children, zinc deficiency can lead to growth retardation. In 2017, the indication for zinc acetate dihydrate (NOBELZIN®) was expanded from Wilson's disease to include hypozincemia, leading to wider use of zinc acetate dihydrate. At five years after this broadening of use, we conducted a post-marketing study (PMS) to investigate the utilization, safety, and effectiveness of zinc acetate dihydrate. Over 52 weeks, the overall incidence of adverse drug reactions (ADRs) was 9.4% (87/928). The most common ADR was copper deficiency (2.4%), followed by nausea (1.4%). Among 928 patients, 19 (2%) developed serious ADRs. Of the patients with copper deficiency, 92% were >65 years of age, and all had comorbidities at baseline. Physicians evaluated the effectiveness of zinc acetate dihydrate using three categories: "effective", "not effective", and "indeterminate". The overall efficacy rate was 83.0%. The average serum zinc levels were elevated from 50-60 μg/dL to >90 μg/dL within 12 weeks, and were maintained up to 52 weeks after administration. Among the symptomatic sub-categories, the efficacy rate was highest in pressure ulcer (96.2%; 25/26), followed by in stomatitis (87.5%; 42/48), and taste disorder (87.4%; 181/207). Among pediatric patients with developmental symptoms, an efficacy rate of 66% was achieved. In conclusion, zinc acetate dihydrate has been safely used, and has produced beneficial effects on various diseases and symptoms.

Effects of rifampicin on the pharmacokinetics and safety of carotegrast methyl in healthy subjects: A randomized 2 × 2 crossover study.

To evaluate the effect of the combination of carotegrast methyl with rifampicin, a potent inhibitor of organic anion transporter polypeptide, on the pharmacokinetics (PKs), safety and tolerability of carotegrast methyl. In this 2 × 2 crossover study in 20 healthy Japanese adults, 10 subjects received carotegrast methyl 960 mg and rifampicin 600 mg on day 1 and received carotegrast methyl 960 mg on day 8. The subjects in the other sequence received the same treatments but in the opposite order. The 90% confidence interval (CI) of the geometric mean ratio of the Cmax and AUC0-t for carotegrast, the main active metabolite of carotegrast methyl, with/without rifampicin was calculated. If the 90% CI fell within the range of 0.80-1.25, this indicated the absence of any drug-drug interaction. Adverse events (AEs) were monitored. The geometric mean ratios (90% CI) of the Cmax and AUC0-t for carotegrast with/without rifampicin were 4.78 (3.64-6.29) and 5.59 (4.60-6.79), respectively, indicating that carotegrast has a PK interaction with rifampicin. The combination with rifampicin increased the exposure of carotegrast and also that of its metabolites. The incidence of any AEs with/without rifampicin was five (25.0%) and one (5.0%), respectively. Coadministration of carotegrast methyl with rifampicin significantly increased the exposure of carotegrast compared with carotegrast methyl administration alone. In this single dose study, the incidence of AEs of carotegrast methyl with rifampicin increased compared with carotegrast methyl alone, but the incidence of adverse drug reactions did not increase with combination administration.

A Prospective Observational Study on the Prescription Pattern of Anticancer Drugs and Adverse Reactions of Chemotherapy in Patients with Breast Cancer

Background: Every hospital should conduct a periodic study of prescription patterns as a potential tool for determining the function of pharmaceuticals in society. Objective: The study’s primary goals were to evaluate prescription patterns and frequent adverse reactions in individuals undergoing breast cancer chemotherapy. Materials and methods: At the American Oncology Institute in Guntur, a prospective observational study was carried out. The breast cancer patients who met the inclusion criteria underwent a six-month period of purposive sampling in a daycare centre. Information about the patient’s demographics, recommended medications, and adverse responses was gathered using a standard data collection form. Results: The study included 230 patients with breast cancer who, according to the study, were found to be in the 50–60year age range. Of the 230 patients, 117 had left breast cancer and 113 had right breast cancer; 226 of the patients were female and 4 were male. The most frequently used chemotherapeutic agent was cyclophosphamide (26%), which was followed by docetaxel (19%) and Adriamycin (14%). Adriamycin + Cyclophosphamide was the most frequently suggested regimen, followed by Docetaxel + Carboplatin + Trastuzumab. The most often reported ADR was nausea, which was followed by alopecia, fatigue, vomiting, and skin rashes. Conclusion: The medication most frequently prescribed was cyclophosphamide. ADR incidence was highest when cyclophosphamide and Adriamycin were used. Despite receiving prophylactic antiemetic medication, the majority of patients experienced nausea and vomiting. This suggests that more steps should be taken to prevent emesis, as these adverse drug reactions (ADRs) associated with antineoplastic medicines are typically avoidable. Keywords: breast cancer, prescription medications, anti-cancer drugs, breast cancer therapy, adverse effects.

Long-Term Safety and Effectiveness of Tacrolimus in Patients With Lupus Nephritis in Japan: 10-Year Analysis of the Real-World TRUST Study.

To assess the long-term safety and effectiveness of tacrolimus as maintenance therapy in patients with lupus nephritis (LN) receiving treatment in real-world clinical settings in Japan. An open-label, noncomparative, observational, prospective postmarketing surveillance study was conducted in 1395 patients with LN receiving maintenance treatment with tacrolimus at 278 medical institutions across Japan over a period of 10 years. Tacrolimus continuation rate and cumulative incidence of adverse drug reactions (ADRs), relapse, progression to renal failure, and progression to dialysis were calculated using Kaplan-Meier analysis. Safety data were available for 1355 patients, almost half (49.3%) of whom remained on tacrolimus for the full 10 years of follow-up. A significant reduction in mean (SD) daily oral corticosteroid dose was observed from 16.0 (9.7) mg/day at 4 weeks after initiation of tacrolimus treatment to 7.2 (4.4) mg/day at year 10 (P < 0.001). The most frequently reported serious ADRs were infections (reported for 131 [9.7%] patients). Except for infections, no marked increase in the incidence of any other ADRs was seen over time, including renal impairment, malignant tumors, and cardiac dysfunction. Renal function was generally well maintained over the 10 years of follow-up. At year 10, cumulative rates of relapse, renal failure, and dialysis were 44.5%, 12.2%, and 4.5%, respectively. Tacrolimus was effective and generally well tolerated as maintenance therapy for LN in a large cohort of patients in Japan followed for 10 years, almost half of whom remained on therapy for the entire duration of follow-up. (ClinicalTrials.gov: NCT01410747).

Real-World Safety and Effectiveness of a 4-Factor Prothrombin Complex Concentrate in Japanese Patients Experiencing Major Bleeding: A Post-marketing Surveillance Study.

Limited data are available regarding the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) in patients experiencing major hemorrhage or requiring expeditious surgical intervention, both globally and within Japan. We executed a prospective, observational post-marketing surveillance study of patients receiving 4F-PCC for the first time between September 19, 2017 and August 15, 2018 in Japan. Patients were subjected to a comprehensive follow-up for a duration of 4weeks. Of 1381 eligible patients, 1271 (92%) received a vitaminK antagonist. Among these, 58% were aged ≥ 75years, 49% manifested atrial fibrillation, 17% presented with valvular heart disease, and 6% exhibited venous thromboembolism. The median (range) international normalized ratio was 2.67 (0.96-27.11) at baseline and 1.21 (0.45-6.61) at first measurement post-administration of 4F-PCC. The most common reason for 4F-PCC administration was intracranial hemorrhage (59.6%), followed by gastrointestinal bleeding (6.6%). Hemostatic effectiveness was achieved in 85.8% of patients. The incidences of adverse drug reactions (ADRs) and serious ADRs were 3.9% and 2.8%, respectively. Thromboembolic events (TEEs) occurred in 20 (1.5%) patients, with a mean onset of 10days. The majority of TEEs were classified as nervous system disorders (55%). At the time of TEE, only 13% of patients resumed anticoagulant therapy. The incidence of TEEs following treatment with 4F-PCC did not surpass those observed in phase3 trials. No novel safety signals were identified. The safety and effectiveness of 4F-PCC in Japanese real-world practice were in harmony with the observations of prior studies.

Machine learning and bioinformatic analyses link the cell surface receptor transcript levels to the drug response of breast cancer cells and drug off-target effects.

Breast cancer responds variably to anticancer therapies, often leading to significant off-target effects. This study proposes that the variability in tumour responses and drug-induced adverse events is linked to the transcriptional profiles of cell surface receptors (CSRs) in breast tumours and normal tissues. We analysed multiple datasets to compare CSR expression in breast tumours with that in non-cancerous human tissues. Our findings correlate the drug responses of breast cancer cell lines with the expression levels of their targeted CSRs. Notably, we identified distinct differences in CSR expression between primary breast tumour subtypes and corresponding cell lines, which may influence drug response predictions. Additionally, we used clinical trial data to uncover associations between CSR gene expression in healthy tissues and the incidence of adverse drug reactions. This integrative approach facilitates the selection of optimal CSR targets for therapy, leveraging cell line dose-responses, CSR expression in normal tissues, and patient adverse event profiles.

Adverse drug reactions attributed to generic substitution of antiretroviral medications among HIV treatment and pre-exposure prophylaxis clients in British Columbia, Canada.

In British Columbia, antiretrovirals (ARVs) for HIV treatment (HIV-Tx) and pre-exposure prophylaxis (PrEP) are free-of-charge through publicly-funded Drug Treatment Programs (DTPs). When available, less costly generics are substituted for brand-name ARVs. We describe the incidence and type of product substitution issue (PSI) adverse drug reactions (ADRs) attributed to generic ARVs. Cohorts included DTP clients ≥19years who received generic ARVs for HIV-Tx (abacavir-lamivudine, emtricitabine-tenofovir DF, efavirenz-emtricitabine-tenofovir DF, atazanavir or darunavir between 01 Jun 2017 and 30 Jun 2022) or PrEP (emtricitabine-tenofovir DF, 01 Apr 2018 to 30 Jun 2022). Demographic, ARV and ADR data were extracted from DTP databases and summarized by descriptive statistics. PSI incidence was calculated for each product during the year following brand-to-generic and generic-to-generic transitions (first-year-post-rollout), and compared between generic versions using generalized estimating equations. For context, incidence of any ARV product-related ADR was calculated in the same 1-year periods. During first-year-post-rollout periods, 5339 HIV-Tx (83% male, median age 52years) and 8095 PrEP (99% male, median 33years) clients received generic ARVs, and reported 78 and 23 generic PSIs, respectively. PSI incidence was <1% for most generic ARVs, with mild-moderate symptoms including gastrointestinal upset, headache, dizziness, fatigue/malaise and skin rash. In HIV-Tx clients, the efavirenz-containing product had higher PSI incidence than other ARVs (2.2%, p = .004), due to more neuropsychiatric adverse reactions. Any ADR incidence was stable across measurement periods, and generic PSIs represented less than one third of all product-related ADRs. Generic substitution of antiretrovirals for HIV-Tx and PrEP was well tolerated, with ≤2% incidence of mild-moderate PSI ADRs.

Time to develop adverse drug reactions and associated factors among children HIV positive patients on antiretroviral treatment in North West Amhara Specialized Hospitals: Retrospective cohort study, 2022.

Adverse drug reactions (ADRs) are harmful and unintended reactions to medicines given at standard doses through a proper route of administration for the purpose of prophylaxis, diagnosis, or treatment. The objective of this research paper was to assess median time to development of ADRs and associated factors among children HIV positive patients on antiretroviral treatment (ART) in North West Amhara Specialized Hospitals. The adverse drug effect survival time was estimated using the Kaplan-Meier survival method and log-rank test curves was applied for analyze "time-to-event" data. Cox regression model was used to identify the associated factors. Adjusted hazard ratios with their respective 95% confidence intervals (CIs) were estimated and a value of p less than 0.05 was used to declare the presence of a significant association. The overall incidence of ADRs was 0.67 (95% CI: 3.74-4.44) per 10,000 person-year observation, with a median of 57 months. Adults are presenting with opportunistic Infections (OIs) experiences, baseline CD4 < 200 cells/µL counts, 1e, tenofovir disoproxil fumarate-lamivudine-efavirenz ART regimen, bedridden baseline functional status, World Health Organization (WHO) clinical stage II and III were notably associated with the incidence of ADRs development. ADRs were uncommon in this study. predictors, such as OIs experiences, a low CD4 count, ART regimen, an advanced WHO stage, and bedridden functional status were significantly associated with ADRs.

A retrospective and observational study of the adverse drug reactions reported in a tertiary care hospital

Background: Adverse drug reaction (ADR) is considered a common cause of prolonged hospitalization and death among patients. Pharmacovigilance is essential in the surveillance of adverse drug reactions. The responsibility of a healthcare professional is to report any adverse reaction that occurs with the use of drugs. This helps in providing a database and improving the safety of patients. The aim of the study was to determine the incidence of ADR, assess causality, severity, and preventability of the submitted adverse drug reactions, increase the awareness of preventability of adverse drug reactions in health care professionals by conducting regular workshops on ADR, and document occurrence of a rare ADR. Methods: A retrospective observational study was conducted to assess the ADR reported to the ADR monitoring Centre, for the past 6 years included in the study. The data were entered into Microsoft excel and analyzed using descriptive statistics. Mean and standard deviation were calculated for the categorical data. Drugs were classified according to the class. Reactions were analyzed using scales and presented in descriptive statistics. Results: A total of 95 ADR reports were received and reported. These ADRs were associated with a total of 108 drugs that were prescribed- the occurrence of ADRs dominated among females 60% (57). Antimicrobials were causing the highest number of adverse reactions 21 (19.44%) and antituberculosis drugs and radiocontrast media were associated with the following larger number of the ADRs 19 (17.59%).  Intravenous at 40% was the most common route related to the development of ADR. The most common ADR caused by antimicrobials was rash (9), antitubercular therapy commonly caused hepatitis, and chills and rigors were more common with radiocontrast media. Most of the reactions observed in the patients were moderate reactions at 52.63% with 3.16% fatal ones. Conclusions: In this study, the predominant causative drugs associated with ADR were antimicrobials, antitubercular drugs, and radiocontrast media. The number of ADRs reported though was less there was a wide range of drugs causing ADR that were reported which gave a broader spectrum for analysis. There is a requirement for active monitoring of ADRs to understand the occurrence as well as help in prevention.

Towards a better detection of patients at-risk of linezolid toxicity in clinical practice: a prospective study in three Belgian hospital centers.

Introduction: Linezolid is a last-resort antibiotic for infections caused by multidrug-resistant microorganisms. It is widely used for off-label indications and for longer than recommended treatment durations, exposing patients at higher risk of adverse drug reactions (ADRs), notably thrombocytopenia. This study aimed to investigate ADR incidence and risk factors, identify thrombocytopenia-related trough levels based on treatment duration, and evaluate the performance of predictive scores for ADR development. Methods: Adult in- and outpatients undergoing linezolid therapy were enrolled in three hospitals and ADRs and linezolid trough levels prospectively monitored over time. A population pharmacokinetic (pop-PK model) was used to estimate trough levels for blood samples collected at varying times. Results: A multivariate analysis based on 63 treatments identified treatment duration ≥10days and trough levels >8mg/L as independent risk factors of developing thrombocytopenia, with high trough values correlated with impaired renal function. Five patients treated for >28days did not develop thrombocytopenia but maintained trough values in the target range (<8mg/L). The Buzelé predictive score, which combines an age-adjusted Charlson comorbidity index with treatment duration, demonstrated 77% specificity and 67% sensitivity to predict the risk of ADR. Conclusion: Our work supports the necessity of establishing guidelines for dose adjustment in patients with renal insufficiency and the systematic use of TDM in patients at-risk in order to keep trough values ≤8mg/L. The Buzelé predictive score (if ≥7) may help to detect these at-risk patients, and pop-PK models can estimate trough levels based on plasma samples collected at varying times, reducing the logistical burden of TDM in clinical practice.

Treatment outcomes amongst older people with HIV infection receiving antiretroviral therapy.

There is conflicting data regarding the response of older people with HIV (PWH) to antiretroviral therapy (ART). The objective of this study was to evaluate the long-term immunological and virological responses, changes in regimen, and adverse drug reactions (ADRs) in older participants (50+ years) compared with younger (18-34 years) and middle-aged (35-49 years) PWH. A retrospective review of medical records was conducted on 1622 participants who received ART in Yunnan Province, China, from 2010 to 2019. The study compared CD4+ T-cell counts, CD4+/CD8+ ratio, and relative numbers between different groups using the Kruskal-Wallis test. Cox proportional hazards regression models were used to identify variables associated with the occurrence of immune reconstitution insufficiency. The rates of immune reconstitution, incidence of ADRs, and rates of treatment change were analyzed using the chi-squared test or Fisher's exact test. Over 95% achieved viral load 200 copies/ml or less, with no age-related difference. However, older participants exhibited significantly lower CD4+ T-cell counts and CD4+/CD8+ recovery post-ART (P < 0.001), with only 32.21% achieving immune reconstitution (compared with young: 52.16%, middle-aged: 39.29%, P < 0.001) at the end of follow-up. Middle-aged and elderly participants changed ART regimens more because of ADRs, especially bone marrow suppression and renal dysfunction. Although the virological response was consistent across age groups, older individuals showed poorer immune responses and higher susceptibility to side effects. This underscores the need for tailored interventions and comprehensive management for older patients with HIV.

The safety and effectiveness of remdesivir in a postmarketing surveillance study in Japan

BackgroundTo evaluate the occurrence of adverse drug reactions (ADRs) and to assess mortality and health status in participants receiving remdesivir in real-world settings in Japan. MethodsThis postmarketing surveillance study used an all-case surveillance method for enrollment. Participants with SARS-CoV-2 infection administered remdesivir from July 2020 to November 2021 in Japan were eligible for inclusion. The observation period was from remdesivir treatment initiation to 4 weeks after the end of treatment or treatment discontinuation. Clinical status and outcomes were analyzed by Kaplan-Meier plots and compared across subgroups at baseline, Day 14, Day 28, and the final observation point. ResultsThe analysis included 2128 participants (mean age, 67 years; 71.4 % male; 84.1 % with current comorbidities). ADRs and serious adverse drug reactions (SADRs) were reported among 10.4 % and 1.2 % participants, respectively. Overall, 191/2127 participants died (mortality rate [95 % confidence interval], 11.10 [9.66–12.75] per 100 person-months), 1511/2127 showed clinical improvement (117.8 [112.0–123.9] per 100 person-months), 1392/2127 recovered (103.9 [98.6–110.0] per 100 person-months), and 216/324 were extubated (107.0 [93.6–122.3] per 100 person-months). ConclusionsThe incidence of ADRs and SADRs was low, and no new safety concerns were identified. Observed mortality and clinical improvement results were consistent with prior studies, confirming remdesivir's benefits in real-world settings in Japan.

Real-world safety and effectiveness of tenofovir alafenamide for 144 weeks in Japanese patients with chronic hepatitis B.

Tenofovir alafenamide (TAF), a prodrug of tenofovir, delivers high levels of active drug to hepatocytes and is given in a lower dose than tenofovir disoproxil fumarate (TDF). TAF reduces viral replication in patients with chronic hepatitis B (CHB) similar to TDF and has shown a lower risk of the renal and bone toxicities associated with TDF use. This post-marketing surveillance study examined the safety and effectiveness of TAF in treatment-naïve and -experienced CHB patients who received TAF for 144 weeks at real-world clinical sites in Japan. Safety assessments included the incidence of adverse drug reactions (ADRs), renal and bone events, and changes in selected laboratory parameters. Effectiveness was based on the proportion of patients with HBV DNA levels below the lower limit of quantitation or <29 IU/mL. This analysis included 580 patients; 18.4% of whom were treatment-naïve. The cumulative incidence of ADRs was 0.21 per 100 person-months, and the incidence of serious ADRs was 0.01 (95% CI, 0.00-0.04) per 100 person-months. There were no ADRs of declines in estimated glomerular filtration rates, renal failure or proximal tubulopathy. The most common ADR was hypophosphataemia in seven (1.2%) patients. Two (0.4%) patients each had decreased blood phosphorus, bone mineral density decreased, dizziness and alopecia. Overall, the proportion of virologically suppressed patients increased from 68.8% at baseline to 97.5% at Week 144. These results confirm the real-world safety and effectiveness of TAF in Japanese patients with CHB and are consistent with the findings of other evaluations of the safety and efficacy of TAF in CHB.