Adverse Drug Reaction Probability Scale Research Articles

Is hyponatremia caused by Chinese herbal medicine a myth? A scoping review and a review of local data in Hong Kong

AbstractIntroductionHyponatremia is one of the commonly inquired adverse effects related to Chinese herbal medicine (CHM) received by the Hong Kong Poison Information Center. However, it has never been investigated or reviewed systemically. The purpose of this review is to look into the relationship between CHM and hyponatremia.MethodDatabases, including PubMed, the Cochrane library, Embase, and the traditional Chinese medicine database system, were searched for cases reporting hyponatremia after the use of herbs. Inquiries received by the Hong Kong Poison Information Center about CHM‐related hyponatremia from 2008 to 2022 July were reviewed retrospectively by two independent doctors (one physician and one clinical toxicologist) using the Adverse Drug Reaction Probability Scale (Naranjo algorithm). Quadratic weighted Kappa was used to test interrater reliability.ResultsThree case reports or series about herb‐related hyponatremia were identified in the scoping review. Seventy‐two patients with hyponatremia and CHM intake were evaluated to determine the possibility of CHM causing hyponatremia. Around 90% of the patients had biochemical profiles compatible with the syndrome of inappropriate secretion of antidiuretic hormones. Most of the patients had a probability likelihood of “possible” as ranked by the Naranjo algorithm. In 19.5% of the hyponatremic patients taking CHM, no other apparent cause was found.ConclusionThe scarcity of literature in scoping review indicates a potential research gap. CHM might be associated with hyponatremia, for which no alternative cause was found. However, meticulous measures must still be made to determine that no other alternative causes are present in a patient with hyponatremia receiving CHM.

Oral lichenoid drug eruption due to osimertinib for lung cancer.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR) are linked with side effects involving skin and mucosa. Herein, we present a unique case of oral lichenoid drug eruption (LDE) in a patient treated with osimertinib. A 75-year-old woman was diagnosed with metastatic EGFR-mutated lung adenocarcinoma, and started on osimertinib 80 mg PO daily. At 24 months of therapy, the patient developed a painful, red, and white striated oral lesion involving the left buccal mucosa and the adjacent buccal aspect of gingivae. Biopsy showed oral LDE. Causality assessment between osimertinib and the oral LDE via Naranjo Adverse Drug Reaction probability scale revealed a score of 5. Osimetinib discontinuation was not felt to be in the best interest of the patient. Therefore, diphenhydramine HCL mouthwash every 6 h PRN (before meals) was started. Spicy and hot foods were discontinued. At a four-week follow-up visit, the patient reported moderate improvement in her symptoms. Oral LDEs are considered premalignant lesions as they can transform into squamous cell carcinoma; therefore, regular follow-up is needed. Awareness of this potential side effect of osimertinib would also prevent unnecessary (and potentially costly) work-up and lead to its prompt diagnosis and treatment.

CARDIOVASCULAR CONSIDERATIONS IN ANTIDEPRESSANT THERAPY: SINUS ARREST DUE TO SERTRALINE

Abstract A 39–year–old Caucasian woman with a silent cardiac anamnesis and no family history of cardiovascular diseases, and a history of mood disorder treated with Sertraline for about 1 month, went to the Emergency Department reporting several syncopal episode, all with rapid and complete recovery of consciousness. In the Emergency Department, another syncopal episode occurred in the supine position, characterized by sinus bradycardia evolving into a brief asystole, with spontaneous restoration of normal sinus rhythm. Admitted to the Cardiovascular Intensive Care Unit, the patient showed no abnormalities in laboratory testsas well as in echocardiography results. The patient received appropriate hydration, and home medication was discontinued. A non–contrast head CT scan showed no acute lesions. Cardiac MR revealed normal morpho–functional findings, with no evidence of myocardial edema or pericardial effusion and no pathological late gadolinium enhancement areas. Brain MRI demonstrated normal anatomical and functional findings, with no signal abnormalities. Considering the patient‘s young age and the suspicion of an iatrogenic origin of the rhythm disorder, the decision to postpone pacemaker implantation was made, and cardiac electrical activity was monitored using a loop recorder. At the one–month follow–up, the patient, who had been off Sertraline since admission, was in good health, reporting no further syncopal or pre–syncopal episodes. Loop recorder monitoring revealed no significant arrhythmias. The only relevant anamnestic data was the use of Sertraline, and the application of the Adverse Drug Reaction Probability Scale suggests that the iatrogenic origin of this event as a pharmacological adverse effect is at least probable (score: 7). Limited literature connects Sertraline directly to documented cases of asystole, but reports indicate that drugs in the same pharmacological class may induce cardiac rhythm disturbances, including tachyarrhythmias and bradyarrhythmias. This case draws attention to sinus arrest during sertraline therapy and how an appropriate pharmacological washout led to the resolution of the pathology.

Clinical Profile of Patients with Lichenoid Drug Eruption: A Observational Study.

Lichenoid drug eruption (LDE) is an uncommon cutaneous adverse drug reaction, where a variety of drugs used in day-to-day clinical practice have been implicated. To describe the clinico-demographic characteristics of patients with LDE and to identify the most likely drugs involved. In this prospective, observational study, consecutive patients with LDE presenting to the dermatology department of a tertiary teaching hospital were included. The clinico-demographic profile of patients with LDE and implicated drugs was noted. Treatment of drug reaction along with outcome was also documented. Naranjo adverse drug reaction probability scale was used for causality assessment of the drug reactions. A thorough literature review on LDE was also undertaken due to the paucity of existing literature. A total of 15 patients (11 males and 4 females) with LDE were evaluated. Their age ranged from 37 to 61 years, with a mean of 51.53 ± 7.59 years. Anti-hypertensive medications (40%) were the most common culprit agent, followed by antitubercular drugs (33.4%), anti-diabetic agents (13.3%), and others (13.3%). The latent period (time from drug initiation to the appearance of a cutaneous eruption) varied from 15 days to 6 months (mean 2.2 months). Cutaneous involvement was generalized in 73.4% and photo-distributed lesions in 26.6%. Drug provocation test was done to identify the culprit drug. According to the Naranjo adverse drug reaction probability scale, one-third of LDEs were "definite," whereas two-thirds were designated as "probable." LDE is more common in the elderly population. The latent period is comparatively longer in LDE than in other common drug reactions. Prompt recognition and withdrawal of suspected drug are essential to minimize disease morbidity.

P839 Acute interstitial nephritis in patients with Inflammatory Bowel Disease treated with vedolizumab: a systematic review

Abstract Background Acute interstitial nephritis (AIN) is a complication of drugs that may cause permanent kidney injury. AIN has been reported in inflammatory bowel disease (IBD) patients treated with the anti-integrin inbibitor vedolizumab. However, systematically collected data on cases of AIN associated with vedolizumab treatment is lacking. We therefore, through systematic review of existing literature, aimed to identify and describe reported cases of AIN. Methods We searched Medline, Embase, Cochrane, and Web of Science Core Collection between January 1, 2009 and April 25, 2023. The search yielded 1473 publications after deduplication, for which titles and abstracts were screened by two independent reviewers. Of these, 75 publications were reviewed in full-text. Demographics and clinical characteristics of AIN cases were extracted. Case causality assessment was performed according to the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system and the Naranjo Adverse Drug Reaction Probability Scale. Results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A prespecified protocol was registered in the PROSPERO database. Results Eight publications met the inclusion criteria and were included in descriptive analysis of AIN in patients with IBD treated with vedolizumab. A total of nine biopsy-confirmed cases of AIN were reported in six patients with ulcerative colitis and three with Crohn’s disease. The mean age at AIN onset was 36 years (range: 19-58). The majority of patients were females (n=6/9). Time from vedolizumab treatment initiation to AIN onset spanned from hours to 12 months. Common symptoms were fever, malaise, and myalgia. Creatinine levels were elevated in all patients (mean: 219 µmol/L; range; 133-410). Rechallenge after pause and treatment with corticosteroids were reported in three cases, where one attempt was successful. Five patients sustained permanent kidney injury. According to the WHO-UMC scale, six of nine cases were assessed as “possible” or “probable”, and the remaining three cases as “unlikely” or “unclassifiable”. Three patients were treated with concomitant mesalazine or proton pump inhibitors, which both are associated with an increased risk of AIN. Conclusion In systematic review of existing literature, we identified nine cases of biopsy-confirmed AIN in patients with IBD treated with vedolizumab. Our findings suggest that vedolizumab, although rarely, could potentially cause AIN in patients with IBD. Awareness of laboratory findings and symptoms consistent with AIN, along monitoring of the kidney function, could be warranted in patients with IBD treated with vedolizumab.

A CASE POSSIBLE SEROTONIN SYNDROME CASE CAUSED BY COMBINED USE OF FLUOXETINE AND LOW DOSE TRAZODONE AND ASSESSED BY THE NARANJO ADVERSE DRUG REACTION PROBABILITY SCALE

Serotonin sendromu serotonerjik ajan kullanımı sonrasında
 oluşan serotonin reseptörlerinin aşırı uyarılması
 sonucu gelişen nadir görülen fakat mortal seyredebilen
 sendromdur. Klinik belirti ve bulgular kognitif,
 nöromüsküler ve otonomik alanda görülmektedir. Serotonerjik
 etkili bir veya daha fazla ajanın birlikte kullanılması
 bu sendroma neden olur. Klinik görünümü hafif
 şiddette olup gözden kaçabilen olgular olduğu gibi
 hayatı tehdit eden, yoğun bakım ve mekanik ventilasyon
 gerektiren şiddette de olabilmektedir. Bu yazıda
 fluoksetin tedavisine trazodon eklenmesi ve doz artırılması
 sonrasında 24 saat içerisinde gelişen serotonin
 sendromu düşündüren bir vaka sunulmuştur.

Ribociclib-induced pulmonary infiltrates in a patient with breast cancer.

Breast cancer is the most common cancer in women worldwide. One of the treatment choices used in hormone receptor positive and HER2 expression negative metastatic breast cancer is cyclin dependent kinase 4/6 (CDK) inhibitors. There are differences between the effects and adverse events of all CDK4/6 inhibitors. In this report, we describe a 48-year-old female patient with breast cancer who developed pulmonary infiltrates secondary to drug in the second year of follow-up with Ribociclib therapy. The patient who used ribociclib for metastatic breast cancer was admitted to hospital for routine controls. The patient, in the eighth month of ribociclib treatment, had no active complaints. In the patient's imaging, pulmonary infiltrates were detected in the lower lobe of the right lung. The drug was continued in the patient who was asymptomatic and had no infectious signs. Pneumonitis, interstitial lung disease, tuberculosis, COVID-19 and other viral agents were excluded in the patient. A minimal increase in pulmonary infiltrates was observed in the follow-up. However, the patient who does not have any complaints is currently continuing ribociclib at 600 mg/day. The pulmonary infiltrates that developed in the patient increased with continued use of ribociclib, suggesting that this was due to ribociclib. The Naranjo Adverse Drug Reaction Probability Scale also indicates probable relationship.

Validation of Rash and Nonspecific Eruption Diagnoses Using ICD-9 and ICD-10 Codes

Despite being common cutaneous findings in the hospital setting, cutaneous drug eruptions have not been thoroughly validated for administrative claims data. The purpose of this study was to validate primary discharge diagnoses for the ICD code rash or other nonspecific eruptions by finding the positive predictive value (PPV) and to determine how often it was used to indicate an eruption that was eventually determined to be a drug eruption. Two dermatologists independently examined each of 39 hospital patient encounters to assess the validity of the ICD code used by stating whether the code used was appropriate or inappropriate, per table 1 criteria. Since in most patients, a drug eruption was suspected, the Naranjo Adverse Drug Reaction Probability Scale was utilized to externally validate our findings. Our results yielded a PPV for nonspecific rashes of 94.87% (83.11-98.58%) for appropriateness of use. The mean Naranjo score for appropriately versus inappropriately coded cases was 5.7 versus 2.5, respectively, with a mean difference of 3.17568 (0.18833-6.16302), (pooled P-value = 0.0378). Out of the cases analyzed, 29/39 or 74% were confirmed to be drug-related. Our high PPV supports the validity of non-specific eruptions found in national patient databases and the high Naranjo criteria suggest that often, these eruptions are drug related, yet not confirmed at the point of discharge.

Neuropsychiatric adverse reactions in patients treated with denosumab: two case reports and a review of data from the FDA Adverse Event Reporting System (FAERS).

Denosumab is a human monoclonal antibody indicated for patients with osteoporosis and a high risk of fractures. It targets RANKL, the receptor activator of NF-κB (RANK) ligand, blocking RANKL-RANK interaction and leading to rapid osteoclast-mediated bone resorption inhibition. But RANK is widely expressed in neurons, microglia, and astrocytes. RANKL/RANK/NF-κB system can play an important role in the neuroinflammatory response, depressive behavior, memory impairments, and neurotrophism. We present two well-documented case reports of recurrent neuropsychiatric manifestations in patients treated with denosumab and a descriptive review of similar cases reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database between 2012 and 2022. Only those reported by healthcare professionals, coding denosumab as the only suspected drug, were retained. An 81-year-old woman with pre-existing mild cognitive impairment suffered two acute confusional episodes and another 81-year-old woman with depression in remission suffered two depressive recurrences with anxiety and psychomotor inhibition, in both cases following sequential administrations of denosumab without underlying calcium/phosphate imbalance. Scores on Naranjo Adverse Drug Reaction Probability Scale were 6 and 7, respectively, suggesting a probable causal relationship. Of the 91,151 cases with denosumab exposure reported to FAERS, 5.7% were related to psychiatric/neurological disorders and 23.8% of these corresponded to cognitive impairment, depressive/mood disturbances, or psychomotor retardation. Denosumab may cause transient but severe neuropsychiatric symptoms by several mechanisms involving RANKL blockade and subsequent immuno-inflammatory changes, at least in subjects with pre-existing neurobiological vulnerability. We recommend caution and careful monitoring of these patients following denosumab administrations.

Successful desensitization of a patient with hypersensitivity to pertuzumab: a case report

Abstract Introduction: Pertuzumab is a humanized monoclonal antibody used in the treatment of human epidermal growth factor receptor 2–positive early breast cancer. Its use can lead to a type-I hypersensitivity, which can be the result of an IgE-related reaction. This case describes a successful desensitization to pertuzumab in a patient diagnosed with a breast cancer. Method: A patient without a personal history of hypersensitivity and diagnosed with a human epidermal growth factor receptor 2–positive breast cancer was started on chemotherapy with association of trastuzumab, pertuzumab, and paclitaxel. While receiving the fourth cycle of pertuzumab, the patient developed a grade 2 hypersensitivity reaction resolved by the intravenous injection of dexchlorpheniramine and methylprednisolone. A premedication protocol has been setting up with a short desensitization protocol. Results: No adverse event occurred during the desensitization, which permits to continue pertuzumab at normal dose with a low occurrence of adverse events (spontaneous and favorable resolution). On analyzing the suspected adverse drug reaction, the event scored 10 and can found to be considered definite using the Naranjo Adverse Drug Reaction Probability Scale. This successful protocol of desensitization has helped to inhibit a hypersensitivity reaction. The monitoring showed the well-tolerance of the patient. Conclusion: This desensitization avoided a too early changing line treatment, which could have been deleterious. Very few cases of pertuzumab hypersensitivity occurred in France, and none benefited from a desensitization. This case illustrated the fact that rapid drug desensitization is possible, important and a simple opportunity to pursuit effective treatments.

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.

8th ABM/EABM European Regional Conference May 11–13, 2023 Split, Croatia

8^th ABM/EABM European Regional Conference May 11–13, 2023 Split, Croatia

Progressive erythrocytosis under lenvatinib treatment in patients with advanced hepatocellular carcinoma

PurposeThis manuscript reports on the occurrence of early and frequent erythrocytosis in advanced hepatocellular carcinoma (HCC) patients treated with lenvatinib.MethodsA cohort of 23 patients with advanced HCC, treated with this antiangiogenic drug for at least one month, was retrospectively analyzed.ResultsThese patients (82.7% men, median age 58.3, cirrhosis in 60.8%) were treated between October 2019 and September 2020 with lenvatinib, as first-line systemic therapy for 82.6% of them. For 20 patients (87%), an early and significant increase in hemoglobin (Hb) level, up to 1.41 g/dL (p < 0.001) was reported and remained elevated. Ten patients (43.5%), all men, reached erythrocytosis (Hb > 16.5 g/dL), 7 were treated with low-dose aspirin for primary thromboprophylaxis and 2 needed phlebotomy. None underwent thromboembolic complications. A significant Hb decrease was observed after treatment discontinuation (p < 0.05). Erythropoietin (EPO) serum levels also increased, which was attributed to HCC after immunostaining for EPO in liver biopsies. The Naranjo adverse drug reaction probability scale documented the relationship between erythrocytosis and lenvatinib and regression at treatment discontinuation. Erythrocytosis was hypothesized to be a class effect of anti-VEGF therapies, the magnitude of which might depend on the IC50 value of each molecule.ConclusionThis report documents the frequent occurrence of erythrocytosis during lenvatinib treatment for advanced HCC, likely secondary to EPO secretion by tumor cells through the antiangiogenic activity levatinib. An early and close monitoring of hematologic parameters is, thus, recommended, together with thromboprophylaxis by low-dose aspirin and phlebotomy in case of symptomatic erythrocytosis.

Infliximab induced severe depression and suicidal thoughts in patient with bipolar disorder

IntroductionInfliximab is a tumor necrosis factor-alpha (TNF-α) inhibitor commonly used in the treatment of autoimmune disorders such as rheumatoid arthritis and ankylosing spondylitis. An increased risk of opportunistic infections, malignancy, and neurodegenerative diseases have been widely documented as adverse effects of IFX therapy. Few reports exist serving the notice of new-onset psychiatric symptoms linked to IFX treatment, such as suicidal behaviors in adults and elderly patients, as well as psychosis in an adolescent. Psychiatric side effects while under IFX treatment are reported to be rare.ObjectivesHere, we present a case of a female with bipolar disorder who developed a long-standing depressive episode with suicidal thoughts after her fourth infusion of infliximab for her ankylosing spondylitisMethodsRetrospective life chart was created, including infliximab infusion.Montgomery Asberg Depression Scale was applied at time of hospitalisation and discharge.The Naranjo Adverse Drug Reaction Probability Scale was applied.ResultsA 55 year old female with ankylosing spondylitis and bipolar disorder was treated with IFX for 8 months. During this period, a total of 4 infusions were administered and AS symptoms were well responding to the treatment. Patient describes the onset of depressive symptoms such as anhedonia and insomnia after the infusion of third IFX infusion, gradually progressing to loss of function and suicidal thoughts and hospitalization in a psychiatry clinic.The patient had a history of bipolar disorder for 10 years with recurrent manic and depressive episodes, 4 hospitalisations and 1 cure of ECT. Patient was on sertraline, maprotiline and diazepam at the time of hospitalization. We started treatment with aripiprazole, quetiapine and valproate, followed for 4 weeks as an inpatient, consulted with rheumatology treatment options and neurology for demyelinating disorders, no pathology was discovered. Rheumatology suggested the continuation of IFX infusion under psychiatric control. Fifth dose of IFX infusion was administered and patient was discharged after euthymic mood was established and insomnia and suicidal thoughts were deteriorated. Upon follow up, depressive symptoms recurred and lamotrigine was added for augmentation.Image:ConclusionsAlthough there is very scarce evidence that IFX causes psychiatric symptoms, there are few clinical trials too, showing evidence that TNF-alpha inhibitors may improve depressive symptoms. While we need more information and evidence to support the ideas of TNF alpha inhibitors effects on human neuropsychology, it is of great importance for especially patients with psychiatric history to be closely watched while administering the product, at least to minimize unintended adverse events.Disclosure of InterestNone Declared

Recurrent Hyponatremia: Levetiracetam - An Uncommon Cause.

Dear Editor, Hyponatremia can be an adverse drug reaction with the use of some of the anti-seizure medications (ASM). Carbamazepine and oxcarbazepine are the most common ASMs which induce hyponatremia. Rarely sodium valproate, eslicarbazepine, lamotrigine, levetiracetam, and gabapentin have also been reported to cause hyponatremia.[1] We report a case of Levetiracetam induced hyponatremia and review the English literature of similar cases. A 50-year-old male had traumatic brain injury in November 2015 and neuroimaging was normal. He was started on prophylactic levetiracetam at another facility. Since then, he had three admissions for hyponatremia: First admission was for acute symptomatic seizures due to hyponatremia, serum sodium of 118 mmol/L; second admission in February 2016 for dizziness, serum sodium 131 mmol/L; and third admission during April 2016 for drowsiness, serum sodium 108 mmol/L [Table 1]. During the latter two admissions, the work-up for hyponatremia was suggestive of syndrome of inappropriate antidiuretic hormone secretion (SIADH). During the first admission, patient was on levetiracetam 500 mg q12h and the dose was escalated to 1000 mg q12h at discharge. Patient was started on tolvaptan 15 mg q24h at discharge in the first admission (25.12.2015). During his subsequent admissions, workup for other causes of hyponatremia was negative. He was continued with tolvaptan intermittently. Review of the case records and drug chart suggested possible relation between hyponatremia and levetiracetam, a diagnosis of levetiracetam induced hyponatremia was considered and levetiracetam was discontinued. Since then, he had no further episode of hyponatremia. Patient was not started on any ASM as it is not our practice to use ASMs for primary prophylaxis in traumatic brain injury.Table 1: Admission profile of the patientIn this patient, diagnostic workup suggested that SIADH was the possible mechanism for hyponatremia. He had a mild closed traumatic brain injury and normal brain imaging. This clinical scenario is very unlikely to cause SIADH. Workup for other causes of hyponatremia was negative. When levetiracetam was discontinued patient had no further episodes of hyponatremia. On Naranjo Adverse Drug Reaction Probability Scale[2] this patient had a score of 7 suggesting levetiracetam being the “probable” culprit responsible for hyponatremia. Review of English literature revealed report of four patients with levetiracetam induced hyponatremia [Table 2]. In four patients, including the present case SIADH was the mechanism of hyponatremia. There are no specific clinical characteristics which are common among these 5 cases. In all the patients, hyponatremia was corrected after withdrawing levetiracetam. In patient “3” in addition to levetiracetam, hydrochlorothiazide would have added to the misery of hyponatremia.Table 2: Characteristics of the patientsIn conclusion this case illustrates that chronic hyponatremia in a patient with epilepsy on ASMs, one should check the ASM list to exclude the possible drug that can be associated with hyponatremia. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

A naturalistic study on side effects of selective serotonin reuptake inhibitors in psychiatric out-patient department

Introduction: &gt;Antidepressants are one of the most commonly prescribed psychotropic drugs. Six SSRIs are approved for various disorders. SSRIs have fewer side effects owing to its selective blocking the serotonin transporter. Nonetheless SSRI has several troublesome side effects, including nausea, diarrhoea, headache, dizziness, sexual side effects, tachycardia, or weight gain. Methodology: This cross-sectional comprised of 200 patients who were divided into two groups. Group 1 had participants who had received SSRI for less than 6 weeks duration and group 2 had patients who had taken SSRI for more than 6 months. Side effects of medications were recorded using UKU side effect rating scale and causality was ascertained using Naranjo adverse drug reaction probability scale. Results: Among the early side effect group consisting of 100 patients, 40% of patients reported at least one side effect. Tension/inner unrest, nausea and vomiting and orgastic dysfunction was the most common side effect reported. 30% of patients in late side effect group had at least one side effect. Orgastic dysfunction, decreased sexual desire and weight gain were the main side effects reported. All the reported side effects were probably associated due to the prescribed SSRI, as inferred from Naranjo causality scoring system. Conclusion: Escitalopram was the most commonly prescribed SSRI among all the SSRIs. Paroxetine and fluvoxamine were the least prescribed SSRIs. Sertraline was found to cause maximum side effects in the early group and fluoxetine caused the most side effects in the late group. Tension/Inner unrest was the most commonly reported side effects followed by sexual side effects.

Relationship between piperacillin concentrations, clinical factors and piperacillin/tazobactam-associated acute kidney injury.

Piperacillin/tazobactam, a commonly used antibiotic, is associated with acute kidney injury (AKI). The relationship between piperacillin concentrations and AKI remains unknown. Estimate piperacillin exposures in critically ill children and young adults administered piperacillin/tazobactam to identify concentrations and clinical factors associated with piperacillin-associated AKI. We assessed piperacillin pharmacokinetics in 107 patients admitted to the paediatric ICU who received at least one dose of piperacillin/tazobactam. Piperacillin AUC, highest peak (Cmax) and highest trough (Cmin) in the first 24 hours of therapy were estimated. Piperacillin-associated AKI was defined as Kidney Disease: Improving Global Outcomes (KDIGO) Stage 2/3 AKI present >24 hours after initial piperacillin/tazobactam dose. Likelihood of piperacillin-associated AKI was rated using the Naranjo Adverse Drug Reaction Probability Scale. Multivariable logistic regression was performed to identify patient and clinical predictors of piperacillin-associated AKI. Out of 107 patients, 16 (15%) were rated as possibly or probably having piperacillin-associated AKI. Estimated AUC and highest Cmin in the first 24 hours were higher in patients with piperacillin-associated AKI (2042 versus 1445 mg*h/L, P = 0.03; 50.1 versus 10.7 mg/L, P < 0.001). Logistic regression showed predictors of piperacillin-associated AKI included higher Cmin (OR: 5.4, 95% CI: 1.7-23) and age (OR: 1.13, 95% CI: 1.05-1.25). We show a relationship between estimated piperacillin AUC and highest Cmin in the first 24 hours of piperacillin/tazobactam therapy and piperacillin-associated AKI, suggesting total piperacillin exposure early in the course is associated with AKI development. These data could serve as the foundation for implementation of model-informed precision dosing to reduce AKI incidence in patients given piperacillin/tazobactam.

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

Anti-programmed death-1 inhibitor nivolumab-induced immune-related adverse events: hepatitis, renal insufficiency, myositis, vitiligo, and hypothyroidism: a case-based review.

Nivolumab (NIVO) is a monoclonal antibody used to treat renal cell cancer. It is an anti-programmed death-1 (anti-PD-1) inhibitor, enhancing the tumor-targeted immune response of T lymphocytes, resulting in immune-mediated adverse events (AEs). We present five immunologicalAEs in a single patient treated with NIVO. A 68-year-old male patient with metastatic renal cell carcinoma and right-sided nephrectomy received NIVO after pazopanib and sunitinib treatment. Two and a half months after starting NIVO, hepatocellular enzymes and creatinine were elevated. Concomitantly, the patient noticed hypopigmentation of the hand skin and a change in voice and speech. Due to hepatitis, he has been treated with dexamethasone 16mg daily for 22days, after which hypothyroidism and increased creatine kinase were found without muscle pain and functional impairment. Dexamethasone was continued, and a rapid decline in all parameters except thyroid-stimulating hormone (TSH) and vitiligo was observed. Myositis was initially considered a part of hypothyroidism and elevated renal parameters due to hypohydration. The rapid regression on glucocorticoid treatment and a longer time for creatinine normalization than expected with hydration were noticed. Nivolumab likely induced those side effects as assessed by Naranjo Adverse Drug Reaction Probability Scale. The literature review shows that theconsequences of PD-1 inhibition are not uniform. Side effects of checkpoint inhibitors should be monitored carefully in the early and later treatment schedules evaluating subclinical manifestations like myositis and worsening of kidney parameters. Early administered higher doses of glucocorticoids can stop drug toxicity and reverse-induced tissue damage.

Sodium Nitrite Intoxication and Death: Summarizing Evidence to Facilitate Diagnosis.

Over the years, forensic pathology has registered the spread of new methods of suicide, such as the ingestion of sodium nitrite. Sodium nitrite causes increased methemoglobin, resulting in systemic hypoxia, metabolic acidosis, and cyanosis. Since sodium nitrite is a preservative, the ingestion of foods containing an excessive amount of this substance can also cause acute intoxication up to death. The present review is aimed at guiding health professionals in the identification and management of sodium-nitrite-related intoxications and deaths. A systematic literature search was carried out on PubMed by following the PRISMA statement's criteria. A total of 35 studies with 132 cases were enrolled, and the data were cataloged in Microsoft Excel. To establish the causal correlation between sodium nitrite ingestion and death, the Naranjo Adverse Drug Reaction Probability Scale was used. In addition to the small number of cases that have currently been published, the study demonstrated that there was a general methodological discrepancy in the diagnostic process. However, some interesting results have emerged, especially in post-mortem diagnostics. Sodium-nitrite-related deaths represent a challenge for forensic pathologists; therefore, it is important to promptly recognize the essential features and perform the necessary and unrepeatable examinations for the correct diagnosis of the cause of death.