Adverse Drug Reaction Probability Research Articles

Why Pharmacovigilance of Non-steroidal Anti-inflammatory Drugs is Important in India?

Non-steroidal Anti-Inflammatory Drugs (NSAIDs) are among the drugs that are most regularly administered to manage inflammation and pain. Over-the-Counter (OTC) NSAIDs are widely accessible, particularly in developing countries like India. This casual approach to using NSAIDs may operate as a magnet for NSAID-related adverse drug reactions (ADRs) among patients. As patients in India are less informed about the appropriate use of NSAIDs and consumption patttern, adverse drug reactions, and the importance of reporting ADRs, the current study's objective is to promote patient safety by using pharmacovigilance as a tool to educate patients. A targeted literature methodology was utilized to gather the data pertaining to NSAIDs, their ADRs and their pharmacovigilance. Different scientific databases, such as Science Direct, PubMed, Wiley Online Library, Springer, and Google Scholar, along with authentic textbooks, were explored as reference literature. In general, NSAIDs consumption pattern depends upon the different age groups. Around 1.6 billion tablets of NSAIDs are consumed in India for ailments, such as headaches, arthritis, menstrual cramps, osteoarthritis, back pain, rheumatoid arthritis, gout, osteoporosis, tendinitis, cancer pain and chronic pain. Common ADRs of NSAIDs include nausea, vomiting, headache, gastritis, abdominal pain, and diarrhoea. Also, they can cause renal damage and cardiovascular problems if not consumed in a dose-dependent manner. However, Diclofenac and Ibuprofen have both been linked to depression and dementia. There have been reports of aplastic anaemia, agranulocytosis linked to phenylbutazone, Stevens-Johnson, and Lyell's syndrome linked to isoxicam and piroxicam, as well as the vulnerability of new-borns to Reye's syndrome after aspirin use. Lack of awareness, time constraints and unpredictability, poor training in ADRs identification, etc., are some of the reasons for the under-reporting of ADR of NSAIDs in India. In order to rationally prescribe NSAIDs, it is essential to be aware of probable ADR's and establish prescription guidelines. Prescribers' behaviour can be changed toward excellent prescribing practices by conducting routine prescription assessments dealing with NSAIDs and providing feedback. In the near future, it will be critical to strengthen ADR data management and expand the reach of pharmacovigilance programs, ADR monitoring centers, and healthcare professionals' especially pharmacists' training in rural locations.

Concomitant and sequential administration of nirmatrelvir‐ritonavir and azvudine in patients with COVID‐19 caused by the Omicron variant: Safety and efficacy

AbstractBackgroundThis study assessed the safety and efficacy of nirmatrelvir‐ritonavir (Paxlovid®) and azvudine when administered sequentially or concomitantly in patients with coronavirus 2019 (COVID‐19) caused by the Omicron variant.MethodsNinety‐three patients confirmed to be infected with the Omicron variant by nucleic acid detection were retrospectively investigated. Information was collected on general health status, medication, and adverse drug reactions (ADRs) according to whether nirmatrelvir‐ritonavir and azvudine were administered sequentially or concomitantly. Data on times of onset, clinical manifestations, and outcomes of ADRs and on conversion to a negative nucleic acid test were also recorded.ResultsPossible ADRs were recorded in 41 patients (44.1%). There were 22 gastrointestinal reactions in 18 patients and 18 hematological abnormalities in 16 after sequential or concomitant treatment with nirmatrelvir‐ritonavir and azvudine. Liver enzyme levels increased in nine cases and creatinine clearance decreased in two. Cases of atrial fibrillation (n = 1), sleep disorder (n = 2), rash (n = 2), dizziness (n = 1), and weakness (n = 5) were also documented. Only vomiting, poor appetite, diarrhea, xerostomia, bitter taste, and rash were considered probable ADRs; others were thought to be possible ADRs. In all cases, the nucleic acid test did not turn negative after the first antiviral was applied. The nucleic acid test of 28 patients did not turn negative before discharge. The remaining 65 patients (69.9%) returned a negative nucleic acid test after receiving the second antiviral agent.ConclusionsTreatment with nirmatrelvir‐ritonavir and azvudine is safe and effective whether administered sequentially or concomitantly in patients with COVID‐19 caused by the Omicron variant.

Accuracy in patient-reported adverse drug reactions and their recognition: a mixed-methods study.

The causality assessment tool can be utilized to assist patients in identifying adverse drug reactions (ADRs). To evaluate the accuracy of the causality assessment tool for patients identifying ADRs compared to assessments made by pharmacists, and to explore how patients recall and recognize symptoms as ADRs. Mixed methods study consisting of self-administered questionnaires (phase 1) and semi-structured, face-to-face interviews (phase 2) with patients who had experienced ADRs in the past year at a tertiary care hospital in Thailand. Out of 769 questionnaires, 716 were returned and 622 of these were both valid and had at least one ADR (86.8%). Classification of patient-reported symptoms using the causality assessment tool found 12 (1.9%) highly-probable ADRs, 399 (64.1%) probable ADRs, 207 (33.3%) possible ADRs, and 4 (0.6%) that were not classified as ADRs. There was fair agreement between patient-assessed and pharmacist-assessed causality classifications using the Naranjo algorithm (K = 0.268) and the World Health Organization Uppsala Monitoring Centre (WHO-UMC) criteria (K = 0.373). The timing relationship between the occurrence of symptoms and administration of a suspected drug was the most frequently mentioned reason that patients gave for recalling and recognizing suspected ADRs. Promoting the causality assessment tool for use by patients in collaboration with healthcare professionals is likely to enhance patients' ability to correctly identify ADRs and ultimately contribute to increased medication safety.

Meteoric effect of meropenem: an unrevealed case report on Jarisch Herxheimer reaction

Jarisch Herxheimer Reaction is an immune mediated, self- limited reaction that releases endotoxins from the spirochetes. It occurs due to an acute inflammatory response when lipoproteins, owing to their entry into the patient's bloodstream, cause an increase in inflammatory cytokines during the period of exacerbation, resulting in body aches, fevers, rashes, nausea and vomiting, and flushing, along with other symptoms. These symptoms usually begin within 2 hours after the administration of the antibiotics. We represent a 76-year-old male patient who has had a known case of recurrent urinary tract infections since 2017 and was recently diagnosed with urosepsis and syphilis after being administered an injection of Meropenem, wherein he developed a Jarisch Herxheimer Reaction. The causality assessment revealed a Naranjo score of 7, indicating a probable adverse drug reaction. This patient was treated with intravenous antihistamines and corticosteroids for its management. Benzathine penicillin was avoided owing to the previous suspected Jarisch Herxheimer Reaction. None of the studies reported that Meropenem could contribute to such a reaction. All healthcare professionals should maintain a high alert of suspicion and be aware of antibiotic induced Jarisch Herxheimer Reaction symptoms and their management to avoid life threatening conditions.

A case of extrapyramidal side effects due to possible paliperidone: voriconazole interaction

AbstractBackgroundIt is thought that paliperidone, an active metabolite of risperidone, has limited potential for pharmacokinetic drug–drug interactions (DDIs) due to minimal metabolism by cytochrome P450 3A4 (CYP3A4) and cytochrome P450 2D6 (CYP2D6). However, DDIs have been reported and include a theoretical interaction between paliperidone and voriconazole based on interactions between risperidone and strong CYP3A4 inhibitor azoles.AimTo describe the first recorded DDI between paliperidone and voriconazole leading to extrapyramidal side effects (EPSEs).Clinical detailsA 34‐year‐old male presented with febrile neutropenia presumed due to clozapine. Clozapine was ceased and paliperidone commenced with voriconazole added to the patient's empiric piperacillin/tazobactam therapy due to a suspected fungal infection. Two days after starting voriconazole, the patient developed hypertonia and hyperreflexia in all limbs, thought most likely to be antipsychotic induced EPSEs. Paliperidone was withheld and EPSEs resolved.OutcomesThe patient had previously tolerated long‐term paliperidone at higher doses, prior to transitioning to clozapine. The development of EPSEs occurred two days post azole initiation, indicating a probable paliperidone adverse drug reaction (ADR) due to strong CYP3A4 inhibition by voriconazole. This case appears to be the first documented report of this previous theoretical DDI in practice. Further studies, including therapeutic drug monitoring, are required to confirm findings.ConclusionPaliperidone may be affected by pharmacokinetic drug–drug interactions and patients should be monitored for ADRs when CYP3A4 inhibitors are concomitantly administered.

Drug-related deaths in a university hospital: Comparison to previous decades.

The incidence of fatal adverse drug reactions (ADRs) in hospitals varies widely, and ADRs are often underreported. The impact of medical safety processes is not easily evaluated, and although medical practice changes constantly, little is known about ADR trends. This study concentrated on the current incidence and properties of fatal ADRs occurring in a university hospital and compared the results with two previous studies performed in the same hospital. We investigated retrospectively all 1236 deaths that occurred during 2019 in the Helsinki University Hospital. All the cases were evaluated by a team of experts, and the causality was assessed using the categories by World Health Organization and Uppsala monitoring centre. Suicides were excluded. Among death cases, we identified 65 certain or probable ADR cases (5.3%), representing 0.011% of all hospital admissions. Cytostatics and antithrombotics remained the largest drug classes, with neutropenia or sepsis and bleedings as the most common fatal ADRs. Compared with our earlier studies, warfarin caused less, and direct oral anticoagulants caused more fatal bleedings, reflecting the drug usage among the population. In contrast to earlier studies, contrast media and insulin did not cause any fatal ADRs, which may reflect an improvement in pharmacovigilance awareness among healthcare workers.

THU449 An Unexpected Case Of Cutaneous Leukocytoclastic Vasculitis Following Zoledronic Acid Infusion

Abstract Disclosure: B. Zahedi: None. Z.S. Wallace: None. M.M. Cote: None. E.W. Yu: Grant Recipient; Self; Amgen Inc. Background: Zoledronic acid is a potent amino-bisphosphonate frequently used in the treatment of osteoporosis. We report a case of small-vessel vasculitis with cutaneous manifestations occurring after zoledronic acid infusion, previously not reported in the literature. Clinical case: A 58-year old woman with a history of sleeve gastrectomy 1.5 years prior was treated for bone protection with an intravenous infusion of zoledronic acid (Zol) 5mg. This was the patient’s first exposure to a bisphosphonate medication. Within minutes of the infusion, she developed a single episode of diffuse watery diarrhea. Although GI symptoms resolved quickly, within a few hours she experienced generalized myalgias and skin tenderness in her abdomen and extremities, for which she took NSAIDs. These symptoms progressed in severity over the next 3-5 days, manifesting as bilateral hand and lower extremity edema and erythema; no fever/chills/sweats, mucocutaneous ulcers, or urinary symptoms were present. By Day 5, she developed palpable purpura without blanching above the ankles and extending to the knees. By Day 7, prednisone 60mg was started. Prior to Zol, labs showed sufficient 25-hydroxyvitamin D, normal calcium, renal and liver function. On Days 10 and 14, labs revealed AST and ALT, twice and thrice the upper limit of normal respectively. Other notable labs included normal UA, Ca, WBC, eGFR, nonelevated ESR/CRP, and a negative work up for an underlying infectious, inflammatory, ANCA-associated, hypocomplementemic or autoimmune process. Cutaneous findings resolved within 3 weeks of Zol, and transaminitis and edema resolved by week 4. In the setting of a negative lab workup and typical palpable purpura, the patient was diagnosed with leukocytoclastic cutaneous vasculitis (LCV), likely induced by Zol (Naranjo score of 5 consistent with probable adverse drug reaction). Although IgA-mediated Henoch-Schonlein Purpura (HSP) cannot be definitively ruled out in absence of a skin biopsy, the patient did not exhibit other clinical features of HSP, and the timeline is highly suggestive of an idiosyncratic drug reaction whereby Zol acted as a hapton to stimulate an immunologic vasculitis response. Up to 50% of patients with LCV have systemic involvement (renal, GI, pulmonary, cardiac or CNS). Cutaneous LCV usually carries a favorable prognosis after treatment with glucocorticoids. On review of the literature, no prior cases of bisphosphonate-induced LCV have been reported, although there are few cases of giant cell arteritis, uveitis and urticarial vasculitis with bisphosphonate therapy. Conclusions: This is the first case demonstrating cutaneous manifestations consistent with leukocytoclastic vasculitis due to zoledronic acid infusion, which was successfully managed with NSAIDs and glucocorticoids. Clinicians should be aware that LCV may be a rare hypersensitivity complication of Zol. Presentation: Thursday, June 15, 2023

Application of artificial intelligence and machine learning in early detection of adverse drug reactions (ADRs) and drug-induced toxicity

Adverse drug reactions (ADRs) and drug-induced toxicity are major challenges in drug discovery, threatening patient safety and dramatically increasing healthcare expenditures. Since ADRs and toxicity are not as visible as infectious diseases, the potential consequences are considerable. Early detection of ADRs and drug-induced toxicity is an essential indicator of a drug's viability and safety profile. The introduction of artificial intelligence (AI) and machine learning (ML) approaches has resulted in a paradigm shift in the field of early ADR and toxicity detection. The application of these modern computational methods allows for the rapid, thorough, and precise prediction of probable ADRs and toxicity even before the drug’s practical synthesis as well as preclinical and clinical trials, resulting in more efficient and safer medications with a lesser chance of drug’s withdrawal. This present review offers an in-depth examination of the role of AI and ML in the early detection of ADRs and toxicity, incorporating a wide range of methodologies ranging from data mining to deep learning followed by a list of important databases, modeling algorithms, and software that could be used in modeling and predicting a series of ADRs and toxicity. This review also provides a complete reference to what has been performed and what might be accomplished in the field of AI and ML-based early identification of ADRs and drug-induced toxicity. By shedding light on the capabilities of these technologies, it highlights their enormous potential for revolutionizing drug discovery and improving patient safety.

Causality, severity, and preventability of adverse drug reactions due to multi-drug therapy in leprosy: evidence from a national level institution in Sri Lanka

Objective This study describes the causality, severity, and preventability of adverse drug reactions (ADR) in patients affected by leprosy treated with multi-drug therapy (MDT) at the dermatology and central leprosy clinics of the National Hospital of Sri Lanka. Methods This cross-sectional analytical study consisted of two components (retrospective and prospective). Prospective cases were recruited and followed up for six months. Retrospective data collection was carried out at relevant clinics in the NHSL by extracting data from the clinical records of the patients. When an ADR was suspected, it was confirmed after discussion with the clinic medical officers/consultant dermatologist and scored according to the Naranjo ADR probability scale. The intensity of an individual ADR was evaluated using the modified Hartwig and Siegel Severity Assessment Scale, and preventability assessment was performed using the modified Schumock and Thornton scale. Results One hundred and ninety-seven patients were included for ADR attributable to MDT. Approximately 145 patients (73.6%) developed ADR associated with dapsone. Another 50 cases (25.3%) were associated with rifampicin, and 10 (5.1%) were associated with clofazimine. Of the dapsone related 145 ADRs, 59 (40.7%) were definite, 64 (44.1%) were probable, and 22 (15.2%) were possible. Of the rifampicin-related cases, four (8%) were definite, 35 (70%) were probable, and 11 (22%) were possible. The most common adverse drug reactions detected were haemolytic anaemia and hepatic abnormalities due to MDT. Dapsone was discontinued in 40% (59 out of 145) of these patients, while rifampicin was stopped in 8% (4 out of 50) of patients. Clofazimine was not stopped in any of the patients. Conclusions Adverse drug reactions associated with multidrug therapy in leprosy are common among patients diagnosed with leprosy in Sri Lanka. Most ADRs reported in this study were of mild severity and preventable. Careful monitoring and objective scales are needed to identify ADRs at an early stage.

Antibiotics-Related Adverse Drug Reaction in a Tertiary Hospital in Saudi Arabia: A Cohort, Retrospective Study.

Adverse drug reactions (ADR) are caused by a wide range of drugs including antibiotics. Currently, the prevalence and pattern of antibiotic-related ADR in Saudi Arabia are not well reported. The present study aimed to evaluate the ADR pattern caused by antibiotics in a tertiary healthcare center. This was a retrospective study conducted on 85 patients admitted to tertiary care hospitalmedical wards during the period from 2015 to 2019.The following data such as patient demographics (age, gender, weight, height), reason for admission, number of antibiotics use, comorbid condition, antibiotic(s) involved in ADR, classification of ADR, and type of ADR were recorded. Naranjo's scale was used to measure the probability of ADR. Among the 85 patients, the most frequent type of antibiotic was cephalosporins in 36.47%, followed by penicillins in 31.76% of the patients. The major type of ADR was rash (52.95%), followed by anaphylaxis reactions (10.59%) of the patients. Based on the Naranjo scale, the ADR was possible in 80% and probable in 18.82% of the cases. The presence of medical conditions displayed a significant association with the development of rashes (p=0.03). In addition, the female gender (p=0.009) and the presence of medical conditions (p=0.03) showed significant association with the development of anaphylaxis. Cephalosporin and penicillins were the most common antibiotics responsible for ADR, and the rash was the most common ADR.

Neuropsychiatric Adverse Drug Reactions with Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors: An Analysis from the European Spontaneous Adverse Event Reporting System

Tyrosine kinase inhibitors (TKIs) are widely used in gastrointestinal stromal tumors (GISTs). The aim of this study is to evaluate the reporting frequency of neuropsychiatric adverse drug reactions (ADRs) for TKIs through the analysis of European individual case safety reports (ICSRs). All ICSRs collected in EudraVigilance up to 31 December 2021 with one TKI having GISTs as an indication (imatinib (IM), sunitinib (SU), avapritinib (AVA), regorafenib (REG), and ripretinib (RIP)) were included. A disproportionality analysis was performed to assess the frequency of reporting for each TKI compared to all other TKIs. The number of analyzed ICSRs was 8512, of which 57.9% were related to IM. Neuropsychiatric ADRs were reported at least once in 1511 ICSRs (17.8%). A higher reporting probability of neuropsychiatric ADRs was shown for AVA. Most neuropsychiatric ADRs were known, except for a higher frequency of lumbar spinal cord and nerve root disorders (reporting odds ratio, ROR 4.46; confidence interval, CI 95% 1.58-12.54), olfactory nerve disorders (8.02; 2.44-26.33), and hallucinations (22.96; 8.45-62.36) for AVA. The analyses of European ICSRs largely confirmed the safety profiles of TKIs in GISTs, but some ADRs are worthy of discussion. Further studies are needed to increase the knowledge of the neuropsychiatric disorders of newly approved TKIs.

Meta-analysis of the efficacy and adverse drug reactions of adrenergic alpha-antagonists in treating children with ureteral calculi.

This meta-analysis investigated the efficacy and adverse drug reactions (ADRs) of three different adrenergic alpha-antagonists during the treatment of pediatric ureteral stones. Studies were retrieved from MEDLINE, EMBASE, and the Cochrane Controlled Trial Registry until January 2022. We identified 7 articles, including six RCTs and one cohort study. 610 children received either adrenergic alpha-antagonists or placebo. The results confirmed that the three different adrenergic alpha-antagonists could significantly increase the ureteral calculi expulsive rate and shorten the ureteral calculi expulsive time, regardless of the size of the stone "<5 mm" or "5-10 mm". Subgroup analysis suggested that all three adrenergic alpha-antagonists increased the ureteral calculi expulsive rate. Tamsulosin and silodosin also have the effect of shortening ureteral calculi expulsive time, while doxazosin has an insignificant effect on ureteral calculi expulsive time. Besides, tamsulosin and silodosin obviously reduced the number of pain episodes caused by ureteral calculi in children. We analyzed the treatment-emergent adverse events (TEAEs) caused by the treatment of three different adrenergic alpha-antagonists to explore their ADRs. The probability of ADRs was increased after treatment with adrenergic alpha-antagonists. Further subgroup analysis revealed the application of tamsulosin was positively correlated with ADRs in children with ureteral calculi, while the application of doxazosin and silodosin had no statistically significant effect on the probability of TEAEs. In a conclusion, this article systematically analyzed the efficacy and ADRs of three different adrenergic alpha-antagonists, and provided reference and guidance for the application of adrenergic alpha-antagonists to treat children ureteral calculi.

Role of Clinical Pharmacy Services in Healthcare System

Clinical pharmacy services are needed into practice for better pharmacotherapy towards safe and optimal patient care. It takes into account, patient-centred orientation with specialized therapeutic knowledge, experience and judgement to assure prudent patient outcomes. Medication Reconciliation is one of the fundamental responsibilities of clinical pharmacy as it forms the basis for many different clinical pharmacy activities such as patient counselling, therapeutic drug monitoring, and detection and regulation of probable adverse drug reactions; therefore, it is the principal duty of a clinical pharmacist to approve drug orders. In many hospitals, where clinical pharmacy services are not fully established much commitment is needed for betterment and expansion of this system in contemplation of bringing out the benefits of these services for advantage of society. Clinical pharmacy mainly focuses on a patient-oriented attitude. They require regular and frequent interactions with the physicians and other health care providers which contribute to improved quality of care. The provision of pharmaceutical care can result in expanded identification of drugs and dose associated problems in admitted patients. The decision-making process for choosing economical and effective medications can be assisted by pharmacists in order to improve the standard of patient care and clinical results by ensuring that medications are chosen in accordance with local protocols and formularies. Clinical pharmacist plays a key role in the patient safety initiatives, intercepting and acting towards feasible prescribing errors. Clinical pharmacy services can serve as vital contributing factor in the betterment of health care system. Pharmacists have roles and responsibilities both as team members and as individual practitioners ensuring that patients benefit from their pharmaceutical care.

Analysis of Adverse Drug Reactions in Patients with Diabetes Mellitus at Private clinics in Hyderabad, Pakistan

Background: Diabetes is characterized by hyperglycemia, a metabolic disorder resulting from defects in insulin secretion, action, or both. The traditional treatment choices available for diabetes include medications that are oral hypoglycemic agents and insulin. Due to the introduction of several medications during the past 20 years, the identification of adverse drug reactions has gained importance. Aim: The aim of this study was to evaluate the adverse drug reactions among diabetic patients and patients’ variables that were linked to the adverse drug reactions. Study Design: Cross-sectional study Place and Duration of Study: This research was done at private clinics in Hyderabad, Pakistan, from August 2021 to January 2022. Methodology: Three hundred and seventy seven participants and the data regarding baseline characteristics of participants, adverse drug reactions reported were analyzed together with the assessment of causality and severity of unwanted reactions. Results: Two hundred and forty one (63.9%) were males and 136 (36.1%) were females. Only 19 (5%) reported adverse drugs reactions. Hypoglycemia was the most commonly reported adverse drug reaction i.e.11 ((57.9%). On causality assessment, most of the adverse drug reactions fell under the category of probable adverse drug reaction i.e.15 (78.9%). Four (21.1%) of them had the doubtful relation with the medications. The majority of the adverse drug reactions that were reported by the participants were found to be moderately severe 13 (68.4%), when analyzed through severity assessment scale. Six (31.6%) were belonged to mildly severe category. Conclusion: The upper age group, male gender, and diabetes duration of more than 5 years were associated with a higher incidence of adverse drug reactions. This study gave in depth analysis of adverse drugs reactions reported in the patients of diabetes mellitus together with the nature of adverse drug reactions reported. A better patient outcome would result from the clinical pharmacist's active participation in adverse drug resistance. Keywords: Adverse drug resistance (ADR), Diabetes mellitus, Hypoglycemia, Severity

Adverse Drug Reactions Monitoring in New Patients Admitted to the Cardiac Care Unit in a Tertiary Care Hospital

Background: Adverse Drug Reactions (ADRs) are amongst the commonly occurring event in the intensive care unit where patients are mostly on the polypharmacy. They affect the quality of life of patients and increase the burden on the health care system. Aim and Objectives: The study aimed to estimate the incidence of ADRs and to assess the causality and seriousness of such ADRs by using the Naranjo probability scale. A prospective, observational, longitudinal study was conducted on patients admitted to the cardiac care unit over a period of 10 months. ADRs profile was noted by spontaneous and intensive monitoring. For analysis, descriptive statistics with 95% CI were used. Results: A total of 77 ADRs were reported from the 173 patients, out of which 31 patients suffered from ADRs, with an incidence of 17.9%. The gastrointestinal system was the most common affected system followed by the cardiovascular and respiratory systems. When analyzed on the Naranjo ADR probability scale, the majority of the ADRs (67.5%) were rated as probable followed by possible (32.4%). It was observed that the number of drugs used as well as the duration of stay in the hospital, in patients with ADRs, was significantly higher than those who did not have any adverse effect. The pattern and spectrum of ADRs need to be studied further so that their occurrence can be prevented. Conclusion: The study can be useful in identifying and minimizing preventable ADRs and can be an effort to make the use of drugs more rational and safe

Prevalence and associated factors of medication-related problems among epileptic patients at ambulatory clinic of Mettu Karl Comprehensive Specialized Hospital: a cross-sectional study

BackgroundDespite appropriate treatment of epilepsy, the treatment outcome is poor in developing country. Therefore, the study was aimed to identify the magnitude and associated factors of epileptic patients at ambulatory clinic of south western Ethiopian hospital.MethodsA hospital-based cross-sectional study was conducted on epileptic patients who had follow-up at Mettu Karl Comprehensive Specialized Hospital (MKCSH). Data collection was done through patient interview and medical charts review. The pharmaceutical care network Europe foundation classification system was used to assess the drug therapy problem and Naranjo algorithm of adverse drug reaction was employed to identify the probability of adverse drug reaction. The data were analyzed by SPSS version 23 after data were entered by Epidemiological Information (Epi Info) 7.2.1. The multivariable logistic regressions were utilized and P < 0.05 was used to declare association.ResultsOver the study period, more than half of the participants 172(57.7%) were males. The magnitude of drug-related problems was found to be 164(55.0%). Among epileptic patients about 323 drug-related problems (DRPs) were identified on average, 1.084 drug-related problems (DRPs) per patient. The widely occurred types of drug-related problems were needs additional drug therapy 72(22.29%), dose too low 52(16.09%) and dose to high which accounts 50(15.48%). Regarding the predictors of drug-related problems, being a female (AOR = 3.57, 95% CI:1.85–6.88, P ≤ 0.001), having frequent seizures (AOR = 2.47, 95% CI%:1.33–4.61, P = 0.004) and the presence of poly-pharmacy (AOR = 3.57, 95% CI: 1.49–8.5, P = 0.004) were predictors of drug-related problems.ConclusionMore than half of the patients had a drug therapy problem. Number of medications taken by the patients, gender and the seizure frequency had a significant association with occurrence of drug therapy problems (DTPs). Therefore, the pharmaceutical care in general and drug information services in particular should be established to hinder any undesirable medication effects in our study area.

Adverse Drug Reactions at Nonelective Hospital Admission in Children and Adolescents: Comparison of 4 Causality Assessment Methods.

This study aimed to compare assessment methods to determine adverse drug reactions (ADRs) at nonelective hospital admission in pediatric patients, to investigate the interrater reliability of assessment methods in pediatric care, and to analyze symptoms related to ADRs and (suicidal) drug intoxications. For 1 year, the medical records of nonelective patients admitted to a university pediatric department were evaluated for potential ADRs using 4 assessments methods by 1 experienced rater. Krippendorff α was calculated from a sample of 14 patients evaluated by 4 experienced raters to determine interrater reliability. In 1831 nonelective hospital admissions, 63.4% (1161 of 1831) of patients had received at least one drug before admission. We found a potential causal relationship between drugs and symptoms documented at admission and thus potential ADRs according to Naranjo in 23.3% (271 of 1161) of those patients, World Health Organization - Uppsala Monitoring Centre (WHO-UMC) in 22.5% (261 of 1161), Koh in 21.7% (252 of 1161), and Begaud in 16.5% (192 of 1161). The probability rating of the potential causal relationships varied considerably between the methods (Naranjo-Begaud, P < 0.01; Naranjo-Koh, P < 0.001; Koh-Begaud, P < 0.01; Begaud-WHO-UMC, P < 0.01). Acceptable interrater reliability (α ≥ 0.667) was only obtained for WHO-UMC (α = 0.7092). The most frequently identified definite ADR was sedation in 1.5% of all nonelective patients with medication before hospital admission. In 1.2% (22 of 1831) of all nonelective admissions, we found drug intoxications with suicidal intent. The assessment methods showed a high variability in the determination of a potential causal relationship between drug and documented symptom, in the classification of the probability of ADRs, and suboptimal interrater reliability. Thus, their feasibility in pediatric patients is limited.

De novo severe pemphigus vulgaris following SARS‐CoV ‐2 vaccination with BBIBP‐CorV

Pemphigus vulgaris (PV) is a rare, potentially life-threatening IgG-mediated autoimmune disease of stratified squamous epithelia of skin and mucosa. IgG autoantibodies produced against desmoglein 3 and 1, the components of intraepithelial desmosomes, lead to acantholysis causing blisters and erosions.1 PV is a multifactorial disorder with unknown genetic and environmental factors.2 Several reports indicated the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and new-onset PV or aggravation of already existing PV.3 Recently, a few reports associated PV with either Moderna or Pfizer vaccines administration.4-6 Here, we describe a case of severe new-onset PV following Sinopharm COVID-19 (BBIBP-CorV) vaccination. A 76-year-old female patient presented with widespread mucosal erosions and milder cutaneous blisters one month after receiving the second shot of the Sinopharm vaccine. She was a known case of diabetes mellitus, hyperlipidemia, and ischemic heart disease with no history of skin disorder. Her drug history included Glibenclamide, Metformin, Atorvastatin, Metoprolol, and Nitrocontin with no dosage change for at least three years. She did not recall taking any new medication or supplement to trigger the reaction. She complained of severe odynophagia with decreased oral intake. She was afebrile, and her vital signs were within normal range. On physical examination, multiple erosions were noticeable on her oral mucosa, including bilateral buccal, hard and soft palate mucosa (Figure 1A). Glazed erythema and minor erosions were observed on her genital mucosa. Small flaccid blisters and crusted erosions were present on her upper trunk and scalp. After obtaining informed consent, two biopsies were performed from the lesional and perilesional skin. Histopathologic examination of skin biopsy shows suprabasal bullae with acantholysis of keratinocytes and tomb-stone characteristic pattern of the papillary dermis with retained basalis keratinocytes (Figure 1B). Papillary dermis with congested blood vessels resembling villi-like projections is evident and inflamed by lymphocytes and eosinophils. Direct immunofluorescence study reveals intercellular network pattern of immunoreactants (IgG and C3c) (Figure 1C). The anti-desmoglein 1 and 3 antibodies serum levels were negative. Her clinical and histological findings were consistent with PV. In order to determine the causality of this reaction with the previous administration of the BBIBP CorV vaccine, we applied the widely used Naranjo Adverse Drug Reaction (ADR) Probability score. The score result was 5, which corresponds with probable ADR. She partially responded to systemic corticosteroid treatment. Subsequently, she was given 2 g of Rituximab. Since then, she experienced remission, and the dose of prednisolone has been tapered. Skin eruptions have frequently appeared in Covid-19 patients with an overall frequency of 5.95%.3 Afterward, with the initiation of COVID-19 mass vaccination, numerous mucocutaneous symptoms have been reported, presumably induced by these vaccines. These manifestations can either be de novo or exacerbation of previous dermatological disorders.7 The types 1 and 4 hypersensitivities have been suggested for urticaria and injection site reactions, respectively.8 The major reported trigger factors for pemphigus include drugs, vaccines such as influenza, rabies, tetanus, hepatitis B, infections, malignancies, and other autoimmune disorders.9 To date, a few cases of PV have been reported after the COVID-19 vaccines. The first report was the development of oral PV in a woman following the first dose of the AZD1222 vaccine that was completely controlled by topical corticosteroids.6 Solimani et al.4 reported a 40-year-old woman with new-onset PV following BNT162b2, which was controlled by prednisolone and Azathioprine. Koutlas et al.5 reported a 60-year-old man who developed oral PV after receiving the second dose of mRNA-1273 and was treated with prednisolone and Rituximab. COVID-19 vaccines induce the production of neutralizing antibodies against SARS-CoV-2 spike protein. Molecular mimicry is proposed pathogenesis for autoimmune disorders induced by COVID-19 vaccines.8 Cross reaction between spike protein of SARS-CoV-2 virus antibody and tissue proteins like Transglutaminase 2 & 3 and S100B may play a role in developing Bullous pemphigoid and Linear IgA bullous dermatosis following COVID-19 vaccination.10 Although there is no definite link between COVID-19 vaccines and autoimmune blistering disorders, the temporal association of these events can suggest a causative relationship. Authors thank patient for participation in this research project. The authors declare no conflict of interest. Rana Samii wrote the manuscript. Rana Samii, Zahra Saffarian, Alireza Ghanadan, and Hassan Vahidnezhad completed and approved the final version. Experimental data were obtained and collected by Rana Samii, Zahra Saffarian, and Alireza Ghanadan. Data sharing will be available upon request from the corresponding author. Data sharing will be available upon request from the corresponding author.

Fluconazole-Induced adrenal insufficiency following allogeneic hematopoietic cell transplant

Adrenal insufficiency (AI) is a potentially life-threatening endocrine abnormality rarely associated with azole antifungals. Patients undergoing allogeneic hematopoietic cell transplantation (alloHCT) are at high risk of invasive fungal infection and frequently receive azoles. Signs and symptoms of AI, such as gastrointestinal symptoms, lethargy, and electrolyte disturbances frequently overlap with common alloHCT toxicities, such that azole-induced AI may be under-reported in this population. We report the first published case of azole-induced AI following alloHCT. The patient presented with orthostasis and nonspecific gastrointestinal and failure to thrive symptoms in the setting of roughly 6 weeks of fluconazole prophylaxis. The patient was found to have primary AI diagnosed via low serum cortisol and inadequate response to cosyntropin. AI symptoms resolved with hydrocortisone supplementation and recurred upon rechallenge with fluconazole. The patient had fluconazole permanently discontinued with resolution of symptoms. We rate this case as a probable adverse drug reaction on the Naranjo scale. AI may be underreported and misdiagnosed in the alloHCT population given the presence of multiple toxicities with overlapping features. Clinicians must be diligent in investigating adrenal function in patients undergoing alloHCT on azole antifungals who present with symptoms of AI.

Management of Medication-Induced Psychiatric Disorders.

Management of Medication-Induced Psychiatric Disorders.