Severe Adverse Drug Reactions Research Articles

Dealing with adverse drug reactions in the context of polypharmacy using regression models

Polypharmacy in older adults increases the risk of adverse drug reactions (ADRs), but studying this relationship is complex. In real-world data, the high number of medications, coupled with rare drug combinations, results in high-dimensional datasets that are difficult to analyze using conventional statistical methods. This study applies horseshoe and lasso regression for analyzing rare events in polypharmacy contexts, focusing on severe ADRs such as falls and bleedings. These regression models are executed on a multi-center dataset compiling 7175 cases from the ADRED project to detect potential ADR-associated drugs among 100 most common drugs in emergency department admissions. Positive predictors are classified by using 50% and 90% credibility intervals. This study demonstrates that regression models with horseshoe or lasso priors are effective for analyzing ADRs, providing a comprehensive consideration of multiple factors in large, sparse datasets and improving signal detection in polypharmacy, addressing a significant challenge in pharmacovigilance. Both priors yielded consistent and clinically meaningful results. The horseshoe regression resulted in fewer potential positive predictors overall, which could make it suitable as a diagnostic tool. While these regressions generate valuable information, there are still challenges in setting appropriate thresholds for determining and interpreting the positive results.

Severe cutaneous adverse drug reaction to atovaquone/proguanil.

Atovaquone/proguanil is frequently prescribed among travellers to malaria-endemic areas. Side effects most commonly include headaches and gastrointestinal symptoms. Nevertheless, physicians should be aware of possible rare severe cutaneous adverse reactions, in order to facilitate the diagnosis and interrupt the drug rapidly if suspected.

A Rare Case of Tremor Induces by Cycloserine in Drug-Resistant Tuberculosis Patient

Background: Tuberculosis is a contagious disease that generated by Mycobacterium tuberculosis. Drug-Resistant tuberculosis (DR-TB) is inculpated the use of the second-line anti-tubercular treatment which is associated with many drug side effects or so called, Adverse Drug Reactions (ADR). Cycloserine (Cs) is an important drug against drug resistant tuberculosis (DR-TB). Cycloserine has been used in tuberculosis therapy since the late 1950s. Identical with most drug, Cycloserine can cause many Adverse Drug Reactions (ADR). Case Illustration: A 23-year-old woman diagnosed with drug-resistant tuberculosis is undergoing long-term treatment. The patient received treatment for DR-TB with the Bdq-Lfx-Cfz-Cs-E regimen. After the patient underwent the 10th month of advanced phase treatment, the patient complained of shaking in both hands (tremors). The tremor is felt to be more severe in the right hand and the patient cannot grip objects tightly. Discussion: Cycloserine (Cs) play an important role in second-line drug management of DR-TB. Cs-Induced psychosis and other neurological side-effects can be detrimental towards patients yet they are rarely reports in DR-TB cases. Cs is correlated with severe psychiatric cases and Central Nervous System related ADRs. Cs-associated ADR is most likely because of production of gamma-aminobutyric acid as a result of inhibition of glutamic decarboxylase. Study Shown that among 132 patients who reported side effects in the cycloserine group, 2 (1.4%) experienced major side effects, namely tremors. Side effects possibly or probably related to Cs appeared after a median of 71 days (range 10–331 days) of Cs treatment. Conclusion: the drug side effects such as tremors are very rare in drug-resistant tuberculosis patients. In this case, the patient's complaint of tremors could be caused by cycloserine as an anti-tuberculosis drug.

Effectiveness and safety of lower dose sulfamethoxazole/trimethoprim for Pneumocystis jirovecii pneumonia prophylaxis in patients with systemic rheumatic diseases receiving moderate-to high-dose glucocorticoids

ObjectivesTo compare the effectiveness and safety of low-dose sulfamethoxazole/trimethoprim (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in patients with systemic rheumatic disease (SRD) who were receiving glucocorticoids. MethodsWe retrospectively analyzed data obtained from Japanese patients with SRD who received glucocorticoids between January 2006 and April 2024. Patients were divided into two groups based on the initial dose of SMX/TMP: low-dose (one tablet twice weekly on non-consecutive days); conventional-dose (one tablet per day). The primary endpoint was the incidence of PCP after 1 year since the initiation of SMX/TMP. Secondary endpoints were discontinuation rates of SMX/TMP therapy and severe adverse drug reactions (ADRs) after 1 year since the initiation of SMX/TMP in both groups, before and after adjusting for patient characteristics. ResultsA total of 186 patients were included in this study: 60 in the low-dose group and 126 in the conventional-dose group. No patients developed PCP within one year after starting SMX/TMP; however, two patients in the low-dose group required escalation of the SMX/TMP dose to the conventional dose due to subclinical PCP. In the adjusted analysis, the low-dose group had a significantly lower discontinuation rate and a lower incidence rate of severe ADRs than the conventional-dose group. ConclusionsLower-dose SMX/TMP therapy was as effective as conventional therapy for PCP prophylaxis and was associated with lower discontinuation rates in patients with SRD receiving glucocorticoids.

A Retrospective Observational Study of Adverse Drug Reactions (ADR) Reported to ADR Monitoring Centre from 2010 to 2020.

Adverse Drug Reactions (ADR) are one of the essential causes of hospital admissions and pose a significant clinical and economic burden on the healthcare system. The Adverse Drug Reaction Monitoring Centre (AMC) in JIPMER functioning under the Pharmacovigilance Programme of India (PvPI) plays a vital role in ensuring medication safety by routinely detecting and monitoring ADRs. Hence, this study aimed to assess the characteristics of ADR reported from 2010 to 2020 in AMC JIPMER and to detect signals, if any. To study the characteristics of Adverse Drug Reactions (ADR) reported to a regional ADR monitoring center from 2010 to 2020 and to detect signals of disproportionate reporting (SDRs) if any from the reported ADRs. A total of 6007 ADR reports with a single suspect drug were included for analysis from 2010 to 2020. The characteristics of these reports, including patient's age and gender, Number and percentage of ADRs, the causality of ADR using WHO UMC (World Health Organization-Uppsala Monitoring Scale), the seriousness of the ADR, and outcome were collected from the ADR reports. MedDRA (Medical Dictionary for Regulatory Activities) Preferred Terms (PT) were used to classify adverse drug reactions. Causality analysis using the Naranjo Algorithm and Preventability using Modified Schumock and Thornton criteria were performed for the ADRs. The number and percentage of severe ADRs were analyzed. The System Organ class of all the ADRs was enumerated. ADRs not mentioned in the US FDA (United States Food and Drug Administration) product label (unlabelled reactions) were documented. Unlabeled reactions with ≥3 ADR reports were included for signal detection by disproportionality analysis. Antineoplastic drugs, followed by antimicrobials, anticonvulsants, Anti snake venom, and NSAID were the most common drugs implicated in ADRs. Skin and subcutaneous tissue disorders were the most common System Organ Class (SOC) involved in the ADRs. Among the 6007 reports, 19.2% were serious ADRs. Most of the ADR reports were of possible causality followed by probable and certain as per WHO UMC and Naranjo causality scales. Only ten ADRs were preventable and one reaction (Tamoxifen-induced neuropathy) was eligible for signal detection. Disproportionality analysis using a 2x2 contingency table showed insignificant signal detection using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR). Analysis of ADRs from an ADR Monitoring center functioning in a tertiary care hospital shows antineoplastic drugs to be the most common drugs associated with adverse drug reactions, with rash being the most common adverse effect. The majority of the ADRs were not preventable. No Signals of Disproportionate Reporting (SDR) were detected in our study.

Assessment of severity and avoidability of adverse drug reactions in neonates: a reproducibility study of the Hartwig tool and LAAT.

Tools for classifying adverse drug reactions (ADRs) have not yet been validated in the context of the neonatal intensive care unit (NICU). The study aims to investigate the inter-rater reliability of the Hartwig tool and the Liverpool avoidability assessment tool (LAAT) in assessing the severity and avoidability of ADR cases in hospitalized neonates. An observational and prospective study was conducted in the NICU of a maternity hospital in Natal, Brazil. The Hartwig tool and LAAT were employed to assess the severity and avoidability of ADRs, respectively. Three experienced clinical pharmacists independently assessed all ADR cases. Inter-rater reliability was measured using Cohen's kappa coefficient (k) with corresponding 95% confidence intervals (CI). Among 79 ADR cases, the mean gestational age was 29.7 ± 4.4weeks, and the birth weight averaged 1446.0 ± 1179.3g. The assessment of ADR severity using the Hartwig tool revealed a significant overall correlation (overall k = 0.573; 95% CI 0.395 to 0.753) with exact agreement (EA) and extreme disagreement (ED) rates between evaluators of 86.5% and 2.5%, respectively. However, no statistically significant correlation was observed for determining avoidability using the LAAT (overall k = 0.017; 95% CI - 0.048 to 0.082), with an EA rate of 83.6% and ED rate of 10.1%. The Hartwig tool demonstrates good reproducibility among different evaluators in determining the severity of ADRs, unlike the LAAT for assessing avoidability.

Drug-Specific Presentation and Outcome of Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) in Children: A Scoping Review.

Drug Reaction with Eosinophilia and Systemic Symptoms (DReSS) is a severe adverse drug reaction with significant variation between patients concerning presenting symptoms and disease severity. Under the hypothesis that the clinical presentation of DReSS is drug-specific, we performed a scoping review and identified 644 cases of pediatric DReSS. A single implicated drug was present in 262 cases, and drugs with 10 or more cases were included in this analysis (n=224): carbamazepine (n=86), dapsone (n=16), lamotrigine (n=25), phenobarbital (n=38), phenytoin (n=45), and trimethoprim-sulfamethoxazole (n=14). Dapsone was associated with increased organ involvement, the highest mortality rate, and the longest period of hospitalization. In addition, we showed that trimethoprim-sulfamethoxazole was associated with higher rates of auto-immune sequelae. This study confirms that drug-specific features exist and may impact the acute and long-term management of DReSS in children.

Prediction of adverse drug reactions using demographic and non-clinical drug characteristics in FAERS data

The presence of adverse drug reactions (ADRs) is an ongoing public health concern. While traditional methods to discover ADRs are very costly and limited, it is prudent to predict ADRs through non-invasive methods such as machine learning based on existing data. Although various studies exist regarding ADR prediction using non-clinical data, a process that leverages both demographic and non-clinical data for ADR prediction is missing. In addition, the importance of individual features in ADR prediction has yet to be fully explored. This study aims to develop an ADR prediction model based on demographic and non-clinical data, where we identify the highest contributing factors. We focus our efforts on 30 common and severe ADRs reported to the Food and Drug Administration (FDA) between 2012 and 2023. We have developed a random forest (RF) and deep learning (DL) machine learning model that ingests demographic data (e.g., Age and Gender of patients) and non-clinical data, which includes chemical, molecular, and biological drug characteristics. We successfully unified both demographic and non-clinical data sources within a complete dataset regarding ADR prediction. Model performances were assessed via the area under the receiver operating characteristic curve (AUC) and the mean average precision (MAP). We demonstrated that our parsimonious models, which include only the top 20 most important features comprising 5 demographic features and 15 non-clinical features (13 molecular and 2 biological), achieve ADR prediction performance comparable to a less practical, feature-rich model consisting of all 2,315 features. Specifically, our models achieved an AUC of 0.611 and 0.674 for RF and DL algorithms, respectively. We hope our research provides researchers and clinicians with valuable insights and facilitates future research designs by identifying top ADR predictors (including demographic information) and practical parsimonious models.

A carbamazepine metabolite activates NLRP3 and controls skin homing of CD8+ T-cells in SJS/TEN

BackgroundStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe adverse drug reactions with extensive keratinocyte death. Carbamazepine (CBZ), the most commonly implicated drug in SJS/TEN, is metabolized by the cytochrome P450 enzyme 3A4 (CYP3A4) into carbamazepine-10,11-epoxide (CBZE) in the liver. While CD8+ cytotoxic T cells play an important role in SJS/TEN, the underlying mechanism of exuberant immune response by CD8+ T cells in these conditions remains incompletely understood. ObjectivesTo examine the expression of NLRP3 inflammasome and their skin migration in CBZE-induced SJS/TEN. MethodsThe expression of the NLRP3 inflammasome complex in skin lesions, sera, and blister fluids of SJS/TEN patients were analyzed by immunohistochemistry and enzyme-linked immunosorbent assay. NLRP3 formation and CD8+ T cell activation status and their functions were examined by immunoblotting, immunofluorescence, and chemotaxis assays. ResultsThe expression of the NLRP3 inflammasome complex was greatly increased in skin lesions of SJS/TEN patients. Moreover, IL-1β and IL-18 levels in sera and blister fluids of SJS/TEN patients were approximately 3-fold higher than those in healthy individuals, with a linear correlation between IL-1β levels and disease activity. CBZE induced NLRP3 inflammasome formation, upregulated CXCL9/CXCL10 levels, and activated CD8+ cytotoxic T cell functions via IL-1β/IL-1R or IL-18/IL-18R signaling in SJS/TEN keratinocytes, which promoted CD8+ cytotoxic T cell migration in SJS/TEN patients. ConclusionThis study showed that CBZE promoted NLRP3 inflammasome formation and strengthened the activation and function of CD8+ cytotoxic T cells in the skin, which contributed to the initiation and progression of SJS/TEN.

CASE REPORT ON DRESS SYNDROME INDUCED BY ANTITUBERCULOSIS DRUGS

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction characterized by an extensive skin rash in association with visceral organ involvement, lymphadenopathy, eosinophilia, and atypical lymphocytosis. We report a rare case of DRESS Syndrome secondary to anti tubercular treatment (ATT). A 53 year old male with pulmonary tuberculosis (TB) presented with fever, facial puffiness, bilateral pedal edema, itchy exfoliative rashes over face, thorax, abdomen, and extremities for 15 days after about 4 months of starting FDC of ATT. On examination there was hypotension (BP-80/60 mm Hg) and bilateral diffuse symmetrical exfoliative dermatitis over face, chest, abdomen, all 4 extremities sparing flexor aspect of thighs and legs. Investigations revealed eosinophilia, leucocytosis (predominantly lymphocytosis), raised alkaline phosphatase and acute kidney injury. FDC was withheld, skin biopsy was performed and the patient was managed as DRESS syndrome fulfilling diagnostic criteria with oral steroids (prednisolone 1mg/kg/day) and other supportive medications. The patient improved gradually with improvement in most of the symptoms and progressive return of laboratory parameters towards normal level. Individuals diagnosed with pulmonary TB who are undergoing treatment with FDC of ATT have a heightened susceptibility to DRESS. The timely identification and cessation of the offending agent can effectively mitigate mortality.

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.

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.

Deep mutational scanning of CYP2C19 in human cells reveals a substrate specificity-abundance tradeoff.

The Cytochrome P450s (CYPs) enzyme family metabolizes ∼80% of small molecule drugs. Variants in CYPs can substantially alter drug metabolism, leading to improper dosing and severe adverse drug reactions. Due to low sequence conservation, predicting variant effects across CYPs is challenging. Even closely related CYPs like CYP2C9 and CYP2C19, which share 92% amino acid sequence identity, display distinct phenotypic properties. Using Variant Abundance by Massively Parallel sequencing (VAMP-seq), we measured the steady-state protein abundance of 7,660 single amino acid variants in CYP2C19 expressed in cultured human cells. Our findings confirmed critical positions and structural features essential for CYP function and revealed how variants at conserved positions influence abundance. We jointly analyzed 4,670 variants whose abundance was measured in both CYP2C19 and CYP2C9, finding that the homologs have different variant abundances in substrate recognition sites within the hydrophobic core. We also measured the abundance of all single and some multiple WT amino acid exchanges between CYP2C19 and CYP2C9. While most exchanges had no effect, substitutions in substrate recognition site 4 (SRS4) reduced abundance in CYP2C19. Double and triple mutants showed distinct interactions, highlighting a region that points to differing thermodynamic properties between the two homologs. These positions are known contributors to substrate specificity, suggesting an evolutionary tradeoff between stability and enzymatic function. Finally, we analyzed 368 previously unannotated human variants, finding that 43% had decreased abundance. By comparing variant effects between these homologs, we uncovered regions underlying their functional differences, advancing our understanding of this versatile family of enzymes.

Adverse drug reactions and drug-related problems with supportive care medications among the oncological population

AimThe current study emphasizes the impact of adverse drug reactions (ADRs) and Drug-Related Problems (DRPs) caused by supportive care medications administered with chemotherapy.MethodThis is a longitudinal observational study carried out at the Ramaiah Medical College Hospital in Bengaluru, Karnataka, India, at the Department of Oncology. The data was recorded using a specifically created data collecting form. Based on the PCNE (Pharmaceutical Care Network Europe), DRPs are identified. The WHO probability scale, Modified Hartwig and Siegel for ADR severity assessment, Naranjo's algorithm for causality assessment, Rawlins and Thompson for predictability assessment, and Modified Shumock and Thornton for preventability assessment were all utilized. The OncPal guideline was considered in terms of the precision of supportive care medications regarding the reduction of ADRs in cancer patients.ResultWe enrolled 302 patients,166 (55%) female and 136 (45%) male (SD 14.378) (mean 49.97), patients with one comorbidity 59(19.6%) and multimorbidity (two or more) 45(14.9%), the DRPs identified were found to be 153 (50.6%); only P2 (safeties of drug therapy PCNE) were considered in this study. ADRs which are identified 175(57.9%) contributed/caused by the supportive care medications. WHO probability scale: 97 (32.1%) possible and 60 (19.9%) unlikely; Naranjo’s algorithm: 97 (32.1%) unlikely and 69 (22.8%) possible; ADR severity assessment scale (Modified Hartwig and Siegel): 95 (31.5%) mild and 63 (20.9%) moderates; Rawlins and Thompson for determining predictability of an ADR: 33 (10.9%) predictable and 137 (45.5%) non-predictable; and Modified Shumock and Thornton for determining preventability of an ADR: 81 (26.8%) probably preventable and 90 (29.8%) non-preventable. The statistical comparison through preforming t-test and measuring Chi-Square between group with ADRs and without ADRs shows in some variables, significantly (Alcohol consumption status, P = .019) and Easter Cooperative Oncology Group (ECOG) performance status P < 0.001.ConclusionComprehensive assessment of supportive medications in cancer patients would enhance the patient management and therapeutic outcome. The potential adverse drug reactions (ADRs) caused by supportive care medications can contribute to longer hospital stays and interact with the systemic anti-cancer treatment. The health care professionals should be informed to monitor the patients clinically administered with supportive medications.

Mechanisms Underlying the Protective Effects of Obeticholic Acid-Activated FXR in Valproic Acid-Induced Hepatotoxicity via Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations.

Valproic acid (VPA)-induced hepatotoxicity is among the most common and severe adverse drug reactions, limiting its clinical application. Recent studies have suggested that activating the farnesoid X receptor (FXR) could be a promising therapeutic approach to alleviate VPA-induced hepatotoxicity; however, related research remains limited. This study aims to comprehensively investigate the mechanisms underlying FXR activation by obeticholic acid (OCA) for the treatment of VPA-induced hepatotoxicity. Network pharmacology was performed to identify potential targets and pathways underlying the amelioration of VPA-induced hepatotoxicity by OCA. The identified pathways were validated through GEO data analysis, and the affinities between OCA and potential key targets were predicted using molecular docking as well as molecular dynamics simulations. A total of 462 targets associated with VPA-induced hepatotoxicity and 288 targets of OCA were identified, with 81 shared targets. KEGG pathway and GO enrichment analysis indicated that the effect of OCA on VPA-induced hepatotoxicity primarily involved lipid metabolism, as well as oxidative stress and inflammation. The results from GEO data analysis, molecular docking, and molecular dynamics simulations revealed a close association between bile secretion, the PPAR signaling pathway, and the treatment of VPA-induced hepatotoxicity by OCA. Our findings suggest that OCA exhibits potential therapeutic efficacy against VPAinduced hepatotoxicity through multiple targets and pathways, thereby highlighting the therapeutic potential of FXR as a target for treating VPA-induced hepatotoxicity.

Patients with severe cutaneous adverse drug reactions have extremely high hair cortisol concentrations that do not correlate with the presence of depression

Patients with severe cutaneous adverse drug reactions have extremely high hair cortisol concentrations that do not correlate with the presence of depression

Diclofenac-induced Acute Generalized Exanthematous Pustulosis: A Rare Case Scenario

ABSTRACT Diclofenac, categorized as a nonsteroidal anti-inflammatory drug, is commonly employed in medical settings due to its effectiveness in alleviating pain and reducing inflammation. Despite its widespread usage, diclofenac is associated with a range of adverse drug reactions (ADRs). Acute generalized exanthematous pustulosis is an infrequent and serious skin condition marked by the abrupt appearance of multiple sterile pustules on an inflamed, red base. This case report seeks to illuminate a unique and severe adverse drug reaction directly linked to diclofenac use, underscoring the importance of increased awareness among healthcare practitioners regarding the varied and occasionally serious nature of ADRs associated with diclofenac.

Adverse events associated with benznidazole treatment for Chagas disease in children and adults.

Chagas disease (ChD) affects approximately 7 million people in Latin America, with benznidazole being the most commonly used treatment. Data from a retrospective cohort study in Argentina, covering January 1980 to July 2019, was reanalysed to identify and characterize benznidazole-related adverse drug reactions (ADRs). The study included 518 patients: 449 children and 69 adults (median age in children: 4years; adults: 25 years; age ranges: 1month-17.75 years and 18-59 years, respectively). The median benznidazole doses received were 6.6mg/kg/day for at least 60 days in children and 5.6mg/kg/day for a median of 31 days in adults. Overall, 29.34% (152/518) of patients developed benznidazole-related ADRs, with an incidence of 25.83% (116/449) in children and 52.17% (36/69) in adults (odds ratio [OR] = 0.32, 95% confidence interval [CI] = 0.19-0.54, P < .001). The incidence rate was 177 cases per 1000 person-years (95% CI = 145-214) in children and 537 per 1000 person-years (95% CI = 360-771) in adults. There were 240 ADRs identified, primarily mild to moderate. Severe ADRs occurred in 1.11% (5/449) of children and 1.45% (1/69) of adults. The skin was the most affected system. A total of 10.23% (53/518) of patients discontinued treatment. More adults than children discontinued treatment (OR = 3.36, 95% CI = 1.7-6.4, P < .001). Although 29.34% of patients experienced ADRs, most were mild to moderate, indicating a manageable safety profile for benznidazole. While optimized dosing schedules and new drugs are needed, avoiding benznidazole solely due to safety concerns is not justified.

A rare case of drug-induced agranulocytosis: A challenging diagnosis andmanagement approach

Agranulocytosis is a severe adverse drug reaction characterized by a significant decrease in the number of neutrophils, making patientshighly susceptible to infections. I present a rare case of drug-induced agranulocytosis in a 45-year-old male patient who presented witha sudden onset of fever, sore throat, and severe fatigue. Infectious and autoimmune etiologies were ruled out by thorough examinations.A thorough medication history indicated that a new drug for the treatment of hypertension had just been started (chlorthalidone). Thepatient was immediately placed on broad-spectrum antibiotics and granulocyte colony-stimulating factor after the medication wasrapidly stopped. The patient’s neutrophil count gradually increased with prompt management, and he displayed clinical improvement.This instance emphasizes the value of prompt diagnosis and treatment of drug-induced agranulocytosis to avert potentially fatalconsequences.

Insights into Patient Experiences with Facilitated Subcutaneous Immunoglobulin Therapy in Primary Immune Deficiency: A Prospective Observational Cohort

BackgroundImmunoglobulin G replacement therapy (IgRT), intravenous (IV) and subcutaneous (SC) routes, is pivotal in treatment of primary immunodeficiencies (PID). In recent years, facilitated subcutaneous immunoglobulin (fSCIG), a combination of rHuPH20 and 10% IgG has emerged as a delivery method to combine advantages of both IV and SC.MethodIn an observational prospective cohort, we investigated patient experience with fSCIG in PID patients from 5 PID centers for up to 12 months. We assessed the efficacy and safety of this treatment with patient/caregiver- and physician-reported indicators. Additionally, we analyzed patient treatment satisfaction (TSQM-9) and quality of life (QoL).ResultsWe enrolled 29 patients (22 pediatric and 7 adults; 14 females and 15 males; (median: 15, min–max: 2–40.9 years) who initiated fSCIG as IgRT-naive (n = 1), switched from conventional rapid-push 10% SCIG (n = 6) or IVIG (n = 22). Among the participants, 19 (65%) exhibited antibody deficiencies, 8 (27%) combined immunodeficiencies, and 2 (7%) immune dysregulations. Remarkably, targeted trough immunoglobulin G levels were achieved under all previous IgRTs as well as fSCIG. No severe systemic adverse drug reactions were documented, despite prevalent local (%86.45) and mild systemic (%26.45) adverse reactions were noted with fSCIG. Due to mild systemic symptoms, 2 patients switched from fSCIG to 10% SCIG. The patient satisfaction survey revealed a notable increase at 2-4th (p = 0.102); 5-8th (p = 0.006) and 9-12th (p < 0.001) months compared to the baseline. No significant trends were observed in QoL surveys.ConclusionfSCIG demonstrates admissable tolerability and efficacy in managing PIDs in addition to notable increase of patients’ drug satisfaction with IgRT. The identified benefits support the continuation of this therapy despite the local reactions.