Drug Reactions Research Articles

Identifying the Burden of Inappropriate Prescribing Using Consensus in a Day Hospital Setting

Abstract Background Inappropriate prescribing (IP) is highly prevalent in older adults and is associated with increased risk of adverse drug reactions, increased morbidity, mortality and healthcare utilisation. Risk factors associated with IP include older age, polypharmacy and having multiple healthcare providers. The aim of our study was to identify the prevalence of polypharmacy and potential IP in the day hospital setting. Methods Patients attending our day hospital over two months were included. Consensus was reached between two Geriatric medicine SpRs and the day hospital pharmacist regarding various categories of potentially IP, and a proforma was agreed. We gathered demographic data, number of medications and subjective medication burden. We recorded data in Excel, and we quantified potentially inappropriate medicines and categorised all identified IP. Results 179 participants were included, mean age 83 (range 68-98). 80% of patients were taking ≥5 medications, overall, 40% perceived they were taking too many. 79% of participants had at least one example of IP, 25% had ≥3. The commonest example of IP involved PPIs, involving 26% participants, followed by antihypertensives involving 21% of participants. Overall, 48% of potentially inappropriate medications were identified due to ‘inappropriate indication’, and 37% related to side-effects. People aged 65-69 and 90-94 were the most likely to report they were taking too many medicines, 75% and 46% respectively. This correlated with the same age brackets having the highest number of average IP, 2.75 and 2.2 respectively. Conclusion Despite the well-known associated risk of harm, our study confirms ongoing high prevalence of polypharmacy and IP amongst older adults. Prescriber vigilance is key in reducing harm. Regular presence of a pharmacist, liaising strongly with medical staff, is invaluable in the day hospital setting.

Genetic Background of Medication-Related Osteonecrosis of the Jaw: Current Evidence and Future Perspectives

Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1, VEGFA, and CYP2C8. With the development of molecular biology, newer methods such as miRNA and gene expression studies have been introduced in MRONJ, in addition to methods that can examine the base sequence of the DNA. Describing the complex genetic background of MRONJ can help further understand its pathophysiology as well as identify new therapeutic targets to better manage this adverse drug reaction.

Prevalence of Adverse Drug Reactions in Hospital Among Older Patients with and Without Dementia.

Older inpatients with dementia are at an increased risk of an adverse drug reaction (ADR) during hospitalization. To quantify the prevalence of ADRs in older inpatients according to dementia status and ADR definition approach and to identify risk factors of ADRs during hospitalization. This was a retrospective cohort study of 2000 inpatients aged ≥ 75 years admitted consecutively to six Sydney hospitals (1 July 2016 to 31 May 2017). Dementia was defined by diagnosis in electronic medical records. ADRs were defined according to two approaches: the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) and classification by a research pharmacist (subset cohort, n = 600). A binary logistic regression was conducted to determine risk factors of ADRs. Among 2000 patients, 25.9% (n = 517) were reported to have dementia. ADRs defined by ICD-10-AM were identified in 8.3% (n = 43) and 14.6% (n = 217) of inpatients with and without dementia respectively (p < 0.001). A total of 13.0% (n = 260) and 12.5% (n = 75) of patients had ADRs defined by ICD-10-AM and a research pharmacist, respectively. Key risk factors of ADRs were longer hospital stay [odds ratio (OR) 1.01, 95% confidence interval (CI) 1.01, 1.02) and a greater number of regular potentially inappropriate medicines (PIMs) on admission (OR 1.17, 95% CI 1.00, 1.38). ADRs were more prevalent among inpatients without dementia and when assessed by a research pharmacist. Our findings underline the need for improved ADR detection in older inpatients.

DRESS syndrome and tuberculosis: Implementation of a desensitization and re-desensitization protocol to recover antituberculosis drugs in a case series at a specialized TB Unit in Lima, Peru.

Antituberculosis drugs (ATDs) could cause severe and rare reactions, such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome. Recovering ATDs might guarantee a higher cure rate for tuberculosis patients. Our aim was to evaluate the results of desensitization and re-desensitization to recover ATDs in a case series of patients with DRESS syndrome. A retrospective case series study was conducted on patients with DRESS syndrome due to therapy with ATDs from 2021 to 2023. Desensitization and re-desensitization protocols, designed with an algorithm proposed by the Tuberculosis Specialized Unit of the Dos de Mayo National Hospital in Lima, Peru, were implemented. A total of 18 patients underwent desensitization or re-desensitization protocols, achieving an overall success rate of 72.2%. The average time for the development of DRESS syndrome due to ATDs was 19 days. Rifampicin (84.2%), isoniazid (68.4%), and pyrazinamide (26.3%) were identified as the main drugs responsible for this adverse reaction. All patients presented with fever and skin rash, with an average eosinophil percentage of 16.7% (interquartile range: 4.5-28.8). Organ involvement (liver, kidney, and heart) was observed in 8 patients, but only 2 patients experienced severe complications due to DRESS syndrome. A significant association was found between the number of ATDs used and eosinophil levels (P =.03). The study introduced a desensitization and re-desensitization algorithm for the treatment of DRESS syndrome, notable for its safety, adaptability, and high success rate. This advancement provided healthcare professionals with safer and more effective therapeutic approaches for managing this complex condition.

¿Pero esto qué es? ¿El ácido valproico es el culpable?

Acute pancreatitis in children can result from a wide variety of etiologies, one of them being drug toxicity. Although the list of medications associated with acute pancreatitis is extensive, the literature provides stronger evidence for drugs such as 6-mercaptopurine, azathioprine, angiotensin-converting enzyme (ACE) inhibitors, metronidazole, asparaginase, acetaminophen and valproic acid. Valproic acid is a drug frequently used in pediatrics. Although most side effects associated with its use are benign, it may also be linked to severe adverse reactions. The most commonly reported include hepatotoxicity, teratogenicity, and acute pancreatitis. Valproic acid-induced acute pancreatitis is thought to occur due to an idiosyncratic reaction, which is independent of drug levels in the blood and can happen at any time during treatment.

Effectiveness and safety of Tachosil® as a ventricular sealant: an observational cohort study.

Surgery close to or in contact with the ventricular system is challenging due to the complications. We sought to evaluate the effectiveness and safety of TachoSil® as a ventricular sealant in preventing complications after cranial surgery with an open ventricular system (OVS). This is a single-center and prospective cohort study We included patients who underwent elective surgery for supratentorial craniotomy and periventricular pathology between December 2020 and November 2023. We registered surgical complications arising from CSF dynamics (such as percutaneous cerebrospinal fluid (CSF) leakage, hydrocephalus, pseudomeningocele), infections, and other complications (postsurgical hematoma) adverse drug reactions (ADRs), reintervention or hospital readmission up to 90days after surgery. Forty interventions were performed on 39 patients, whose median age was 56years. Eleven patients (28.2%) had antecedents of previous surgery in the same location, 5 (12.8%) had previously received radiotherapy and chemotherapy, and 11 (28.2%) were smokers. Twenty-four patients (60%) underwent surgery for high-grade glioma, 8 (20%) for low-grade gliomas, 6 (15%) for metastasis and 2 (5%) for meningioma. Throughout the study and up to 90days after surgery, none of the patients presented an ADR. Only 2 patients (5%) presented with a surgery complications derived from ventricular opening (one patient with a percutaneous CSF leakage and one patients with external hydrocephalus). Both patients resolved with a ventriculoperitoneal shunt. TachoSil® is a dural sealant that can be used safely and effectively intraparenchymally in patients whose surgery involves a ventricular opening. Only 5% of treated patients presented complications arising from CSF hydrodynamics. No patients had pseudomeningocele, infections or complications related to the use of this sealant. To confirm these positive results, randomized and comparative clinical trials assessing the efficacy of TachoSil® in patients after cranial surgery with an OVS are essential. This study was registered in the Clinical Trials.gov (NCT05717335). Date May 1st, 2022.

Drug-induced hypersensitivity syndrome due to phenytoin: Case report and review of the literature.

Drug hypersensitivity syndrome (DIHS) is a rare but potentially fatal adverse drug reaction characterized by fever, rash, and visceral organ damage, particularly affecting the liver. Early recognition and appropriate management are crucial to prevent serious complications. However, there is limited information on the clinical presentation and management of DIHS, especially in the context of antiepileptic drugs. This case report aims to highlight the importance of recognizing subtle clinical signs and symptoms of DIHS, which can be easily overlooked, particularly in the context of antiepileptic drug use. We report a case of a 15-year-old male patient who developed DIHS after being prescribed phenytoin sodium for epilepsy. The patient presented with symptoms of fever, sore throat, rash, jaundice, and liver dysfunction. Initially, the patient did not receive glucocorticoids and experienced additional reactions to cefoxitin and phosphatidylcholine, likely due to cross-reactivity. The diagnosis of DIHS was made based on the patient's clinical presentation, including fever, extensive rash, organ involvement, and hematological abnormalities. The temporal association with the use of phenytoin sodium, along with the exclusion of other causes of fever and rash, supported the diagnosis. Upon initiation of glucocorticoid therapy with dexamethasone, the patient's symptoms significantly improved. The rash and pruritus decreased, and laboratory values showed improvement, with a decrease in liver enzymes and normalization of white blood cell counts. The patient's fever resolved within 48 hours of starting corticosteroids, and there was no evidence of ongoing inflammation as indicated by a decrease in C-reactive protein levels. Furthermore, the patient's 30-month follow-up revealed no recurrence of rash, liver dysfunction, or organic damage, indicating the long-term effectiveness of the treatment administered. This case highlights the importance of recognizing the subtle clinical signs and symptoms of DIHS, especially in the context of antiepileptic drug use. It underscores the potential benefits of early initiation of glucocorticoid therapy in managing DIHS. The case also serves as a reminder of the potential for drug cross-reactivity in DIHS and the need for cautious drug selection during the acute phase of the syndrome.

Dermatological manifestations, and drug-induced reactions in COVID-19 patients: an observational study from İstanbul, Turkiye

Aims: The systemic and respiratory clinical manifestations of coronavirus disease 2019 (COVID-19) include fever, cough, sneezing, sore throat, rhinitis, dyspnoea, chest pain, malaise, fatigue, anorexia, and headache. Moreover, cutaneous manifestations have been observed in 0.2% to 20.4% of cases. This investigation further explores the dermatological manifestations associated with COVID-19 and reactions induced by its pharmacological treatments. Conducted at a university hospital, the study examined 841 patients and identified skin manifestations in 1.5% of cases. It differentiates between symptoms directly attributed to the viral infection and those arising from treatment, highlighting the need for clinical vigilance and adaptability in managing these manifestations. COVID-19 has been linked to a wide range of clinical symptoms, extending beyond the well-known respiratory effects to include various dermatological manifestations. These manifestations, which range from mild rashes to severe conditions like vasculitis, may complicate diagnosis and management, particularly when similar symptoms are induced by therapeutic drugs used in COVID-19 treatment. Methods: This cross-sectional study included 841 patients treated in the COVID-19 outpatient and inpatient units of the university hospital between March and May 2020. The assessment involved clinical examinations and telemedicine consultations, focusing on differentiating between viral and drug-induced dermatological reactions. Results: Dermatological manifestations were observed in 1.5% of the 841 patients. Direct virus-related skin changes were noted in 1% (n=8) of patients, including maculopapular eruptions (50%, n=4) on the face and trunk, trunk-localized urticaria (25%, n=2), and purpuric lesions (12.5%, n=1) on the lower extremities. Drug-induced dermatological reactions were identified in 0.5% (n=5) of patients, featuring conditions such as bullous drug reactions, psoriasiform drug eruptions, hypertrichosis, and urticaria. Conclusion: These findings highlight the complex interplay between COVID-19 and its treatment, where both the virus and pharmacological agents can trigger significant dermatological reactions. The need for healthcare providers to consider both viral and drug-induced factors in the diagnosis and management of skin manifestations in COVID-19 patients is underscored. Further studies are essential to refine treatment protocols and reduce adverse dermatological outcomes.

Exploring the factors influencing the health-related quality of life in patients experiencing adverse drug reactions: a cross-sectional study

BackgroundThis study aimed to assess the factors influencing health-related quality of life (HRQoL) in patients experiencing adverse drug reactions (ADRs) at a tertiary care public sector hospital. A cross-sectional study was conducted over a period of 18 months, and included both male and female patients aged 18 years and above. Patients who visited the outpatient and inpatient departments with complaints associated with ADRs were included in this study. HRQoL data were collected using the EuroQol—5 Dimension—5 Level (EQ-5D-5L) questionnaire to assess five dimensions of health on a five-level scale. Descriptive statistics, t-tests, and analysis of variance were used to analyze the data. Multivariate regression analysis was performed to identify the potential determinants of HRQoL.ResultsA total of 316 patients were included in the study among these participants, of which 54% were female, and 65% were from rural areas. The majority (68%) of the patients had moderately severe ADRs, and 63% of the participants had an income < 2.5 lakh Indian rupees (3009 USD). The mean EQ-5D-5L and EuroQoL Visual Analog Scale (EQ VAS) scores of the study participants were 0.714 and 69.73, respectively. The variables ADR severity, income, and age showed a significant difference (p < 0.05) in HRQoL.ConclusionThis study provides insights into HRQoL among patients with ADRs and identifies the determinants of HRQoL. The findings of this study will contribute to improving patient-centered care and optimizing patient outcomes.

Efficacy of Ciprofloxacin in Treating Gram-Negative Infections: Does Obesity Matter?

Obesity is considered a health issue associated with increased morbidity and a risk factor for multiple conditions, such as type 2 diabetes, cardiovascular diseases and infections. It may affect the pharmacokinetics and pharmacodynamics of many drugs, including antimicrobials like ciprofloxacin. Regrettably, data on ciprofloxacin's efficacy in obese patients remain scarce. This study aims to evaluate the impact of obesity on the efficacy of ciprofloxacin in treating Gram-negative bacterial infections. A retrospective multicenter cohort study was conducted in two tertiary hospitals in Saudi Arabia. Adult patients (≥18 years) treated with ciprofloxacin for confirmed Gram-negative infection between January 2017 and April 2023 were included. Patients were excluded if they received ciprofloxacin empirically, had inadequate source control within 72 h, or had missing weight and height information at ciprofloxacin initiation. The primary outcome was clinical cure, defined as the resolution of the clinical infection manifestations without additional therapeutic management by the end of treatment. Other secondary and safety outcomes were also assessed. A total of 99 patients were included, divided into obese (n = 42) and non-obese (n = 57) groups. The obese group had a significantly lower median age (50 years) compared to the non-obese group (64 years) (p = 0.002). The obese group had fewer male patients (38.10% vs. 68.42%; p = 0.004), higher body weight (90 (81-97) vs. 63 (55-70) days; p < 0.001), and lower height (158 (155-165) vs. 165 (158-172) days; p = 0.008) compared to non-obese. Urinary tract infection was the most common type, with Escherichia coli being the most common isolate. The median hospital length of stay was shorter in the obese group than in the non-obese group (1 vs. 3 days, p = 0.007). There were no significant differences in clinical cure rates between obese (85.71%) and non-obese (85.96%) patients (p = 1). No significant differences were observed in terms of in-hospital mortality, 30-day mortality, or 60-day infection recurrence rates between the two groups. Microbiological eradication was not achieved in the obese group, whereas a 10.53% eradication rate was observed in the non-obese group (p = 0.037). However, the majority of the patients had indeterminate eradication. The incidence of adverse drug reactions (ADRs) was lower in the obese group (4.76%) compared to the non-obese group (17.54%, p = 0.066). Treatment with ciprofloxacin in obese patients has similar efficacy and safety outcomes compared to non-obese patients with infections due to Gram-negative pathogens.

Early Oral Step-Down Versus Continued Intravenous Antibiotic Treatment of Complicated Intra-Abdominal Infection.

Background: Complicated intra-abdominal infections (cIAIs) require a combined tactic, of source control and antimicrobial therapy. This study aimed to evaluate the safety and efficacy of oral step-down antimicrobial therapy in cIAIs after initial intravenous (IV) antimicrobial therapy. Methods: This retrospective cohort study included hospitalized adult patients diagnosed with a cIAI who received more than seven days of IV therapy from March 2017 to October 2021. Exclusion criteria included primary/peritoneal dialysis-related peritonitis, necrotizing pancreatitis, fistulizing inflammatory bowel disease, or upper gastrointestinal tract infection. Patients were assigned into two groups: IV-only or oral step-down therapy. The primary outcome was infection recurrence, defined as re-initiation of antimicrobial agents after a treatment-free period of more than or equal to three days. Secondary outcomes included treatment escalation, repeat source control procedure, treatment-related complications, and all-cause mortality. Results: The cohort consisted of 248 patients (199 IV-only and 49 oral step-down). Patients receiving IV-only therapy had a shorter median antimicrobial duration than the oral step-down group (13 vs. 23 d; p <0.0001). Infection recurrence occurred in 26 (13.1%) and 6 (12.2%) patients in the IV-only and oral step-down groups, respectively (p = 0.88). Treatment escalation, repeat source control, and 28-day mortality were similar between groups. Oral step-down therapy resulted in more adverse drug events (10.2% vs. 3.0%; p = 0.04). Discussion: Transition to oral step-down after initial IV therapy had a similar rate of infection recurrence as IV-only therapy but was associated with a longer duration of antimicrobial therapy and an increased rate of adverse drug reactions. Larger randomized non-inferiority studies are needed to confirm this approach.

Prescription pattern of usage of analgesics in pain relief in cancer patients at a tertiary care teaching hospital - An observational prospective study

Objective The World Health Organization has developed guidelines for the pharmacological and radiotherapeutic management of cancer pain in adults and adolescents to provide evidence-based guidance to healthcare providers on the adequate relief of pain associated with cancer. This prospective study was done to evaluate the prescription pattern of analgesics for the treatment of cancer pain. Material and Methods This prospective observational study was conducted in cancer patients attending the pain clinic of the Anesthesia and Radiotherapy Outpatient Department. Approval was obtained from the Institutional Human Ethics Committee. Inclusion criteria were age ≥18 years of either gender, willing to provide written informed consent, and patients undergoing radiotherapy, chemotherapy, or palliative treatment. Exclusion criteria were patients having psychiatric illness, not willing to provide written informed consent, patients having renal and or hepatic dysfunction, patients with comorbidities with chronic pain, and patients who underwent surgical intervention. Results A total of 100 participants were recruited during the study period of July 2022–April 2024 whose data were assessed. Participants were prescribed different classes of analgesic drugs, which included 30% participants on opioid analgesics, 30% on non-opioid analgesics, and 40% on combination therapy. Among opioid analgesics, morphine was the most commonly prescribed. Among non-opioid, paracetamol was the most commonly prescribed. Among combination therapy, tramadol was the most commonly prescribed. Pregabalin was most commonly used as an adjuvant analgesic. Conclusion This study also emphasizes on need for adequate treatment of cancer pain and vigilant monitoring of patients on opioids to prevent drug abuse, drug dependence, and adverse drug reactions.

Unravelling Transplant-Ineligible Newly Diagnosed Multiple Myeloma Treatment in Real-World Practice in Spain: The CARINAE Study.

Real-world evidence on the impact of monoclonal antibodies as first-line treatment in Spain is limited. This observational, retrospective and prospective, multicenter, descriptive study included 117 transplant-ineligible newly diagnosed multiple myeloma (TIE-NDMM) patients divided into Group A, who received no daratumumab standard regimens, and the DVMP group (daratumumab, bortezomib, melphalan, and prednisone treatment). More than 90% of the patients in Group A received bortezomib, lenalidomide, or a combination of them. The median follow-up time for Group A was 38.2 months in comparison to 25.8 months for the DVMP group (p < 0.0001). The rate of DVMP patients that experienced disease progression or death from any cause was 36.8%, compared to 67.3% of Group A patients at 36 months of follow-up. The DVMP group had a higher 36-month progression-free survival (PFS) rate (52.9% vs. 31.7%). During the retrospective period, 73.0% of patients reported adverse drug reactions, while in the prospective period, 40.5% experienced adverse events, with no clinical differences between groups. The study supports the use of daratumumab regimens in frontline therapy based on real-world data. The findings provide valuable insights into the clinical outcomes of daratumumab therapy, which can help physicians make informed decisions regarding the optimal treatment approach for this patient population.

Real-world safety and effectiveness of lenvatinib in unresectable hepatocellular carcinoma in Korea: post-marketing study.

Aim: This post-marketing surveillance study evaluated the safety and effectiveness of lenvatinib as first-line treatment for unresectable hepatocellular carcinoma in Korea.Materials & methods: Adverse drug reactions (ADRs) and other safety and effectiveness end points were assessed in patients who initiated lenvatinib according to the approved label in republic of Korea.Results: Among 658 lenvatinib-treated patients, ADRs were reported in 57.8%; ADRs grade ≥3 in 13.5%. The most common grade ≥3 ADRs were asthenia (1.2%) and hepatic encephalopathy (1.2%). Physician-reported tumor responses (n=511) were complete (1.0%) or partial (12.9%) response and stable (45.2%) or progressive disease (40.9%); objective response rates were higher with longer lenvatinib treatment duration (p<0.001).Conclusion: Lenvatinib was generally well tolerated and effective in real-world clinical practice in Korea.Clinical trial registration: ClinicalTrials.gov NCT05225207.

Scientific Analysis with a Retrospective Method on the Incidence and Severity of Adverse Drug Reactions in Hospitalized Cancer Patients

Adverse Drug Reactions (ADRs) often result from omissions or inadequate use of preventative measures, making them definitely or probably preventable. Discrepancies between clinical severity and patients' perceptions of ADRs' impact on their well-being highlight the need for targeted interventions. This study focused on the frequency, manifestations, and severity of ADRs from chemotherapeutic agents, utilizing a cross-sectional design with data from ADR reports spanning November 2021 to October 2023 at dr. Saiful Anwar General Hospital, Indonesia. A total of 177 ADRs were analyzed descriptively. Of these, 99 (55.93%) occurred in women, with the highest incidence in the 19–60-year age group (77.40%). The most common malignancies were Chronic Myeloid Leukemia (10.17%), Colorectal Malignancy, and Non-Hodgkin Lymphoma (9.60% each). ADRs related to chemotherapy constituted 41.80%, involving drugs such as cisplatin, oxaliplatin, afatinib, imatinib, and Doxorubicin. The severity distribution was 70.37% mild, 27.16% moderate, and 2.47% severe. Monitoring and reporting these ADRs are crucial for patient safety and preventing recurrence.

The Impact of Antibiotic Misuse in Adult Patients: A Review of Contributing Factors, Consequences, and Strategies for Mitigation.

Antibiotic misuse, characterized by inappropriate use, over-prescription, and self-medication, is a severe threat to health in that it increases the rate at which antibiotic-resistant bacteria develop. This paper provides a review of antibiotic misuse concerning adult patients, an outline of factors that perpetuate it, the consequences, and the possible mitigation strategies. We discuss patient-related issues, such as lack of knowledge and non-compliance, problems with healthcare providers in terms of over-subscription and poor training, and system problems like poor stewardship programs and lack of regulatory efforts. In addition, the authors debate the environmental consequences of poor antibiotic stewardship coming from agriculture use and contamination. The consequences of misuse include the development of antibiotic-resistant pathogens and deleterious drug reactions, but also imply significant costs to the health system. The review calls for increased antibiotic stewardship, improved patient education, the development of new antimicrobial agents, and good policy infection control. This review is essence, a call to multifaceted efforts in the fight against the misuse of antibiotics and stresses that continuous research works are required to change policies. Antibiotic misuse is emerging as a global problem because addressing this problem not only ensures sustainability in the existing antibiotics but also assures that public health is protected.

Risks Associated with the Use of Intranasal Corticosteroids: An Analysis of Adverse Reactions Reported to EudraVigilance.

Background: Intranasal corticosteroids (INCS) are used for several conditions, including allergic rhinitis and sinusitis. Consequently, their safety profile needs continuous monitoring. This study aimed to analyse the adverse drug reactions (ADRs) of the INCS with market authorisation in Europe. Methods: A retrospective analysis of the ADR data from EudraVigilance in the period between the 1 January 2011 and 12 June 2023 was performed, with 2641 reports selected for analysis. ADRs were categorised by seriousness and evolution, with a focus on the most prevalent ADRs and their alignment with the Summary of Product Characteristics (SmPC). Results: The 18-64 age group, particularly females, was most affected. Mometasone was the most reported INCS, with predominantly non-serious ADRs, evolving towards resolution, which often were not listed in the SmPC. From the reported ADRs that were not described in the SmPC of the INCS studied, "Anosmia" and "Ageusia" were highlighted. Regarding the ADRs described in the SmPC, the most frequently reported were "Epistaxis" and "Headache". The ADRs belonging to the Designated Medical Event list were also analysed, with "Angioedema" as the most reported ADR, which was mainly associated with budesonide. Conclusions: These findings underscore the importance of continuous INCS monitoring to mitigate ADRs and safeguard public health. Further research is warranted to explore potential novel signs for safety arising from previously unreported ADRs.

Optimizing the individual dosing of paroxetine in major depressive disorder with therapeutic drug monitoring.

Previous studies have examined the correlation between paroxetine concentrations and therapeutic efficacy in patients diagnosed with major depressive disorder (MDD), but findings have been contradictory. This study aimed to investigate the relationships among plasma concentrations, severity of symptoms, and adverse drug reactions (ADRs) to optimize individual dosing. Eighty-seven MDD patients, after completing treatment with paroxetine, were divided into low-concentration (LC, n = 38), medium-concentration (MC, n = 27), and high-concentration (HC, n = 22) groups, based on cutoff value concentrations with the 50% response rate and the laboratory alert level from the 2017 consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology. The severity of depression and anxiety was evaluated using a 17-item Hamilton Depression Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA), respectively. Dosage, plasma concentrations, scale scores, and ADRs were recorded across the three groups at different treatment stages to define the therapeutic reference range. The 4-week plasma concentration of paroxetine (65.00 ng/mL) could predict the clinical response in MDD patients at 8 weeks. Symptom relief in patients with 4-week paroxetine concentrations ranging from 65.00 to 120.00 ng/mL at 8 weeks was greater than in those with concentrations below 65.00 ng/mL, with no significant difference observed above this range. In addition, more cases of liver injury and weight gain were observed in patients with high paroxetine concentrations. Our results support that early paroxetine concentration may predict clinical efficacy and the incidence of ADRs, thus improving individual dosing regimens for MDD patients.

A Knowledge Graph Embedding-based Approach to Predict the Adverse Drug Reactions using a Convolutional Neural Network

A Knowledge Graph Embedding-based Approach to Predict the Adverse Drug Reactions using a Convolutional Neural Network

Safety and efficacy of Lippia multiflora in the management of stage I hypertension: outcomes of a randomised controlled trial

IntroductionHypertension is a growing public health problem in the developing world. The chronic nature of the disease has been a driver for the use of traditional medicines. Clinical validation of such products for their safety and efficacy is thus of public health importance. We report on the clinical safety and effectiveness of a Lippia multiflora-based herbal antihypertensive (LMT-19). MethodsA randomised controlled study was conducted among 80 volunteers clinically diagnosed, per the WHO criteria, with stage I hypertension. Participants received either an aqueous infusion of LMT-19 plus a standard lifestyle and dietary recommendation based on a Dietary Approaches to Stop Hypertension (DASH) diet or the lifestyle and dietary recommendation alone. ResultsThe use of LMT-19 resulted in a significant decline of blood pressure over a 60-day period. Diastolic blood pressure in the LMT-19 group was found to be significantly lower compared to the control (mean diff: 8.25 (±1.50); P ≤ 0.001). Systolic blood pressure was also significantly better compared to the control group (mean diff: 12.70 ± 2.02; P ≤ 0.001). The product was also well tolerated as no adverse drug reactions were also recorded during the study. ConclusionThese outcomes suggest LMT-19 as a potential alternative remedy for management of stage I hypertension. Clinical trial registrationPan-African Clinical Trial Registry, PACTR202107733803271.