Pharmaceuticals (Basel). 2021 Dec 24;15(1):27. doi: 10.3390/ph15010027.

ABSTRACT

In this study, we used the large number of cases in the FDA adverse-event reporting system (FAERS) database to investigate risk factors for drug-induced hiccups and to explore the relationship between hiccups and gender. From 11,810,863 adverse drug reactions reported between the first quarter of 2004 and the first quarter of 2020, we extracted only those in which side effects occurred between the beginning and end of drug administration. Our sample included 1454 adverse reactions for hiccups, with 1159 involving males and 257 involving females (the gender in 38 reports was unknown). We performed univariate analyses of the presence or absence of hiccups for each drug and performed multivariate analysis by adding patient information. The multivariate analysis showed nicotine products to be key suspect drugs for both men and women. For males, the risk factors for hiccups included older age, lower body weight, nicotine, and 14 other drugs. For females, only nicotine and three other drugs were extracted as independent risk factors. Using FAERS, we were thus able to extract new suspect drugs for drug-induced hiccups. Furthermore, this is the first report of a gender-specific analysis of risk factors for hiccups that provides novel insights into drug-induced hiccups, and it suggests that the mechanism responsible is strongly related to gender. Thus, this study can contribute to elucidating the mechanism underlying this phenomenon.

PMID:35056084 | DOI:10.3390/ph15010027

MMWR Morb Mortal Wkly Rep. 2022 Jan 21;71(3):90-95. doi: 10.15585/mmwr.mm7103a4.

ABSTRACT

On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the adenovirus-vectored COVID-19 vaccine (Janssen Biotech, Inc., a Janssen Pharmaceutical company, Johnson & Johnson), and on February 28, 2021, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for its use as a single-dose primary vaccination in persons aged ≥18 years (1,2). On April 13, 2021, CDC and FDA recommended a pause in the use of Janssen COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome (TTS), a rare condition characterized by low platelets and thrombosis, including at unusual sites such as the cerebral venous sinus (cerebral venous sinus thrombosis [CVST]), after receipt of the vaccine.* ACIP rapidly convened two emergency meetings to review reported cases of TTS, and 10 days after the pause commenced, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in persons aged ≥18 years, but included a warning regarding rare clotting events after vaccination, primarily among women aged 18-49 years (3). In July, after review of an updated benefit-risk assessment accounting for risks of Guillain-Barré syndrome (GBS) and TTS, ACIP concluded that benefits of vaccination with Janssen COVID-19 vaccine outweighed risks. Through ongoing safety surveillance and review of reports from the Vaccine Adverse Event Reporting System (VAERS), additional cases of TTS after receipt of Janssen COVID-19 vaccine, including deaths, were identified. On December 16, 2021, ACIP held an emergency meeting to review updated data on TTS and an updated benefit-risk assessment. At that meeting, ACIP made a recommendation for preferential use of mRNA COVID-19 vaccines over the Janssen COVID-19 vaccine, including both primary and booster doses administered to prevent COVID-19, for all persons aged ≥18 years. The Janssen COVID-19 vaccine may be considered in some situations, including for persons with a contraindication to receipt of mRNA COVID-19 vaccines.

PMID:35051137 | DOI:10.15585/mmwr.mm7103a4

J Clin Pharmacol. 2022 Jan 20. doi: 10.1002/jcph.2030. Online ahead of print.

ABSTRACT

Melphalan is an alkylating agent used as part of conditioning prior to pediatric hematopoietic cell transplantation (HCT). We performed a single center, prospective pharmacokinetic (PK) study of 37 pediatric patients undergoing HCT from March 2015 to 2019. The primary objective was to develop and validate a population PK model for melphalan in a diverse group of pediatric HCT recipients. Nonlinear mixed-effects modeling was implemented to describe plasma time-concentration data of melphalan. A two compartment, proportional error model with weight on clearance best fit the data. Final parameter estimates were: clearance 19.1 L/hr/25 kg; volume of the central compartment 8.5 L/25 kg; volume of the peripheral compartment 5.8 L/25 kg; and inter-compartmental clearance, 12.4 L/hr/25 kg. Residual unexplained variability was low at 12.5%. Results suggested the empiric weight-based dosing (mg/kg) used in children less than 12kg or 2 years of age may result in subtherapeutic exposure. Model-based dosing of melphalan in pediatric HCT may help inform individualized dosing strategies to improve clinical outcomes and limit drug-related adverse events in pediatric HCT recipients. This article is protected by copyright. All rights reserved.

PMID:35048362 | DOI:10.1002/jcph.2030

Front Nutr. 2022 Jan 3;8:815456. doi: 10.3389/fnut.2021.815456. eCollection 2021.

ABSTRACT

Antipsychotic drugs (APDs) represent a cornerstone in the treatment of schizophrenia and other psychoses. The effectiveness of the first generation (typical) APDs are hampered by so-called extrapyramidal side effects, and they have gradually been replaced by second (atypical) and third-generation APDs, with less extrapyramidal side effects and, in some cases, improved efficacy. However, the use of many of the current APDs has been limited due to their propensity to stimulate appetite, weight gain, and increased risk for developing type 2 diabetes and cardiovascular disease in this patient group. The mechanisms behind the appetite-stimulating effects of the various APDs are not fully elucidated, partly because their diverse receptor binding profiles may affect different downstream pathways. It is critical to identify the molecular mechanisms underlying drug-induced hyperphagia, both because this may lead to the development of new APDs, with lower appetite-stimulating effects but also because such insight may provide new knowledge about appetite regulation in general. Hence, in this review, we discuss the receptor binding profile of various APDs in relation to the potential mechanisms by which they affect appetite.

PMID:35047549 | PMC:PMC8762106 | DOI:10.3389/fnut.2021.815456

J Crohns Colitis. 2022 Jan 19:jjac013. doi: 10.1093/ecco-jcc/jjac013. Online ahead of print.

ABSTRACT

Therapeutic options for the management of inflammatory bowel disease (IBD) have been expanding in recent decades. New biological and small molecule therapies have been incorporated into the pharmacological arsenal, allowing a more personalized management, seeking increasingly strict remission goals. However, the fear of developing adverse events represents one of the most important limitations in deciding its use by patients and a multidisciplinary team. Despite the risk of hepatotoxicity of thiopurines and methotrexate, these drugs are still used either as monotherapy or as combined therapy with anti-TNF biologic agents. Although drug-induced liver injury (DILI) appears to be less frequent with anti-TNF agents, newer biologics and small molecules, monitoring liver tests should be considered in the follow-up of these patients, especially if in the future raises the option of combined therapy of biologics or these drugs with small molecules. The objective of this review is to show data on the risk of developing DILI in patients with IBD who are undergoing treatment with traditional therapy or new drugs, whether biological or small molecules.

PMID:35044449 | DOI:10.1093/ecco-jcc/jjac013

J Oncol Pharm Pract. 2022 Jan 19:10781552221074046. doi: 10.1177/10781552221074046. Online ahead of print.

ABSTRACT

INTRODUCTION: Leukocytoclastic vasculitis is a histopathological term describing vasculitis in which the inflammatory infiltrate in small vessels consists of neutrophils. Although FLOT is given perioperatively in locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma, it has recently become a popular treatment option for metastatic cancers. In this case report, we present a case of FLOT-induced LCV.

CASE REPORT: We present a 52-year-old patient with metastatic gastric adenocarcinoma treated with FLOT. The patient developed necrotizing vasculitis in the lower extremity after 5 cycles of FLOT.

MANAGEMENT & OUTCOME: After discontinuation of the FLOT regimen, the necrotizing morbid LCV gradually regressed with steroid therapy.

DISCUSSION: To the best of our knowledge, our case is the first case of LCV that developed after FLOT chemotherapy. The clinical appearance of the patient, occurrence after chemotherapy, erythematous rash developing on bilateral lower extremities, and palpable purpuric vasculitis made us suspect. We found a potential relationship between FLOT and vasculitis according to the Naranjo scale (score 4 + ).

PMID:35044279 | DOI:10.1177/10781552221074046

Sci Rep. 2022 Jan 18;12(1):897. doi: 10.1038/s41598-022-04818-7.

ABSTRACT

Sugammadex has been approved for reversal of neuromuscular blockade by vecuronium and rocuronium in adults undergoing surgery. Although widely used in the operating room, sugammadex has not been investigated in the intensive care unit setting. This study aimed to evaluate the use of sugammadex in critically ill patients with a focus on known drug-related adverse reactions. In this single-center, retrospective, observational study, 91 critically ill patients who were administered sugammadex while in the ICU were evaluated. Electronic health records were reviewed, and baseline data, as well as indication and incidence of complications possibly related to sugammadex, were retrospectively collected. The most common procedures requiring neuromuscular blockade followed by reversal with sugammadex were bronchoscopy, percutaneous dilatative tracheostomy, and percutaneous endoscopic gastrostomy. Within 2 h following administration of sugammadex, skin rash and use of antihistamines were reported in 4 patients (4.4%) in total; bradycardia was observed in 9 patients (9.9%), and respiratory adverse events were described in 3 patients (3.3%). New-onset bleeding up to 24 h after sugammadex was reported in 7 patients (7.7%), 3of whom received transfusions of packed red blood cells. Sugammadex was well tolerated in critically ill patients and could be considered for reversal of neuromuscular blockade in this population. Larger prospective studies are required to determine the safety profile and evaluate the potential benefit and indications of sugammadex in the critical care setting.

PMID:35042888 | DOI:10.1038/s41598-022-04818-7

Toxicol Appl Pharmacol. 2022 Jan 15:115886. doi: 10.1016/j.taap.2022.115886. Online ahead of print.

ABSTRACT

Many small molecule kinase inhibitors (SMKIs), used predominately in cancer therapy, have been implicated in serious clinical cardiac adverse events, which means that traditional preclinical drug development assays were not sufficient for identifying these cardiac liabilities. To improve clinical cardiac safety predictions, the effects of SMKIs targeting many different signaling pathways were studied using human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) in combined assays designed for the detection of both electrophysiological (proarrhythmic) and non-electrophysiological (non-proarrhythmic) drug-induced cardiotoxicity. Several microplate-based assays were used to quantitate cell death, apoptosis, mitochondrial damage, energy depletion, and oxidative stress as mechanism-based non-electrophysiological cardiomyocyte toxicities. Microelectrode arrays (MEA) were used to quantitate vitro arrhythmic events (iAEs), field potential duration (FPD) prolongation, and spike amplitude suppression (SAS) as electrophysiological effects. To enhance the clinical relevance, SMKIs induced cardiotoxicities were compared by converting dug concentrations into multiples of reported clinical maximum therapeutic plasma concentration, "FoldCmax", for each assay. The results support the conclusion that the combination of the hPSC-CMs based electrophysiological and non-electrophysiological assays have significantly more predictive value than either assay alone, and significantly more than the current FDA-recommended hERG assay. In addition, the combination of these assays provided mechanistic information relevant to cardiomyocyte toxicities, thus providing valuable information on potential drug-induced cardiotoxicities early in drug development prior to animal and clinical testing. We believe that this early information will be helpful to guide the development of safer and more cost-effective drugs.

PMID:35041852 | DOI:10.1016/j.taap.2022.115886

Platelets. 2022 Jan 18:1-7. doi: 10.1080/09537104.2022.2026910. Online ahead of print.

ABSTRACT

Chemotherapy-induced thrombocytopenia (CIT) is a common complication in cancer patients, especially after multiple cycles of chemotherapy, which leads to the delayed treatment or reduced dosage. The treatment of CIT is limited for refractory and severe cases. Herein we reported a single-center study of avatrombopag, a type of thrombopoietin receptor agonist (TPO-RA), for the treatment of severe and refractory (S/R) CIT who failed from multi-line treatments. A total of 13 cancer patients with S/R CIT were enrolled at the First Affiliated Hospital of Zhejiang Chinese Medical University from September 2020 to February 2021. All the patients were administered oral avatrombopag at an initial dose of 60 mg/day, which could be decreased as needed, over a period of 8 weeks. Eight (8/13, 61.5%) patients responded to avatrombopag (with a platelet count ≥50 × 109/L and transfusion independent), with a median response time of 27.5 (11-50) days, and the median cumulative day of platelet response was 79 (20-167). Ten of 13 patients (76.9%) no longer required platelet transfusion at the study endpoint. The predictor of response was the level of hemoglobin (HB) at study entry, patients with an HB over 90 g/L achieved a response rate of 88.9%. In addition, platelet count showed 87.5% sensitivity and 100% specificity to predict the treatment response at a cutoff value of 25.5× 109/L at the end of the third week management. No drug-related side effects were noticed during administration. Our study showed that avatrombopag could be a novel and effective drug for the treatment of severe and refractory CIT, especially for those with hemoglobin above 90 g/L. This study was registered at chictr.org.cn as # ChiCTR2100050646.

PMID:35040375 | DOI:10.1080/09537104.2022.2026910

J Oncol Pharm Pract. 2022 Jan 17:10781552221074374. doi: 10.1177/10781552221074374. Online ahead of print.

ABSTRACT

INTRODUCTION: Pembrolizumab has been on the market for several years, but most of the safety data is based on clinical trials with limited literature evaluating post-marketing immune-related adverse events (irAEs) associated with its use. This study aimed to evaluate the characteristics of irAEs associated with pembrolizumab.

METHODS: We included adult patients who had received pembrolizumab between January 2016 and December 2020. The patient electronic profiles and the pharmacy adverse event reporting system were reviewed to identify adverse events. Patients were followed from the start of treatment until 12 months after the last dose, end of the study, or death. The characteristics of the patients and the irAEs were recorded. Univariate and multivariate logistic regression analyses were performed to identify variables associated with the development of irAE.

RESULTS: During the study period, 223 patients and 1601 cycles of pembrolizumab were evaluated. A total of 67 irAEs were reported in 58 patients. The median age was 53 years (range 18-84), and most patients were males (75%) with metastatic lung cancer (62%). The most common irAEs were respiratory (30%), followed by gastrointestinal (25%), endocrine (24%), and dermatologic (21%). Among the reported irAEs, 28 were associated with hospital admission, 15 required long-term treatment, and 9 resulted in pembrolizumab discontinuation. In logistic regression, there were no significant predictors associated with irAE.

CONCLUSIONS: Respiratory irAEs were the most common in our population. We were unable to identify predictors of irAE in this cohort. Further studies are necessary to identify predictors of adverse events.

PMID:35037810 | DOI:10.1177/10781552221074374

Int J Hypertens. 2022 Jan 7;2022:2717291. doi: 10.1155/2022/2717291. eCollection 2022.

ABSTRACT

This phase 4 study evaluated the efficacy and safety of azilsartan medoxomil (AZL-M) in patients with essential hypertension and type 2 diabetes mellitus (T2DM) in Hong Kong, Taiwan, and Thailand. This was a prospective, multicenter, single-arm, open-label study with patients aged 18-75 years with T2DM and essential hypertension and on stable treatment for T2DM. Patients with uncontrolled hypertension were treated with AZL-M 40 mg daily, with the option to uptitrate to 80 mg at 6 weeks. In all, 380 of the 478 patients screened in Hong Kong, Taiwan, and Thailand were enrolled. At week 6, 97 patients (25.5%) were titrated up to AZL-M 80 mg based on BP readings. At 12 weeks, 54.8% of patients reached the blood pressure (BP) goal of <140/85 mm Hg by trough sitting clinic BP (primary endpoint), and 62.8% and 27.0% achieved a BP of <140/90 mm Hg and <130/80 mm Hg, respectively. The efficacy of AZL-M over 12 weeks was also seen in different age and body mass index groups. The incidence of treatment emergent adverse events (TEAEs) was 12.9% before 6 weeks and 16.1% after 6 weeks, and they were mostly mild in severity. The most frequent TEAE was dizziness (4.7%). The incidence of TEAEs leading to study drug discontinuation (4.5%) and drug-related TEAEs (5.0% before 6 weeks; 3.9% after 6 weeks) was low. In patients with essential hypertension and T2DM in Asia, treatment with AZL-M indicated a favorable efficacy and safety profile in achieving target BP.

PMID:35036003 | PMC:PMC8759883 | DOI:10.1155/2022/2717291

AIDS Res Ther. 2022 Jan 15;19(1):4. doi: 10.1186/s12981-022-00428-5.

ABSTRACT

BACKGROUND: Raltegravir (RAL) has favorable tolerability and safety profile, with few and manageable drug interactions. The use of RAL 1200 mg once daily (qd) for first-line therapy is well established. We assessed efficacy and safety of RAL 1200 mg qd, as part of triple combined antiretroviral therapy (cART), for maintenance strategy.

METHODS: The QDISS trial (NCT03195452) was a 48-week multicenter, single-arm, open-label study designed to evaluate the ability of 2 NRTIs + RAL 1200 mg qd to maintain virological suppression in HIV-1 infected subjects on a stable cART with 2 NRTIs and a third agent for at least 6 months. The primary endpoint was the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24, by the FDA snapshot algorithm.

RESULTS: Of 100 participants 91% maintained viral suppression (95% CI: 83.6-95.8) at week 24 and 89% (81.2-94.4) at week 48. At week 24, there was one virological failure, without emergence of resistance-associated mutation and 10 participants had discontinued, 4 because of adverse events (AEs). Over 48 weeks, 7 AEs of grade 3-4 were reported, one possibly study-drug related (spontaneous abortion). BMI remained stable regardless of previous therapy or baseline BMI category. Over 48 weeks, total cholesterol (p = 0.023) and LDL-cholesterol (p = 0.009) decreased, lifestyle and ease subscale significantly improved (p = 0.04). The quality of life and Patients Reported Outcomes (PROs) also improved at W12 (p = 0.007).

CONCLUSION: RAL 1200 mg qd as part of a maintenance triple therapy showed a high efficacy in virologically suppressed HIV-1 infected subjects, with good safety profile and improved lipid profile and patient reported outcomes.

TRIAL REGISTRATION: Clinical trials.gov NCT03195452 and EudraCT 2016-003702-13.

PMID:35033092 | DOI:10.1186/s12981-022-00428-5

BMC Health Serv Res. 2022 Jan 15;22(1):79. doi: 10.1186/s12913-022-07494-5.

ABSTRACT

BACKGROUND: Critically ill patients treated in the intensive care units (ICUs) often suffer from side effects and drug-related problems (DRPs) that can be life-threatening. A way to prevent DRPs and improve drug safety and efficacy is to include clinical pharmacists in the clinical team. This study aims to evaluate the classification of drug-related problems and the implementation of clinical pharmacy services by a clinical pharmacist in the ICU of a university hospital in Turkey.

METHODS: This study was carried out prospectively between December 2020 and July 2021 in Gazi University Medical Faculty Hospital Internal Diseases ICU. All patients hospitalized in the intensive care unit for more than 24 h were included in the study. During the study, the clinical pharmacist's interventions and other clinical services for patients were recorded. DRPs were classed according to the Pharmaceutical Care Network Europe V.8.02.

RESULTS: A total of 151 patients were included during the study period corresponding to 2264 patient-days. Patients with DRPs had a longer hospital stay and a higher mortality rate (p < 0.05). 108 patients had at least one DRP and the total number of DRPs was 206. There was an average of 1.36 DRPs per patient, 71.5% of patients experienced DRP and 89.22 DRPs per 1000 patient-days. A total of 35 ADEs were observed in 32 patients. ADE incidence was per 1000 patient-days 15.45. ADEs were caused by nephrotoxicity (48.57%), electrolyte disorders (17.14%), drug-induced thrombocytopenia (17.14%), liver enzyme increase (8.57%) and other causes (8.57%). Drug selection (40.29%) and dose selection (54.36%) constituted most of the causes of DRPs. Dose change was the highest percentage of planned interventions with a rate of 56.79%. Intervention was accepted at a rate of 90.8% and it was fully implemented.

CONCLUSION: In this study, the importance of the clinical pharmacist in the determination and analysis of DRPs was emphasized. Clinical pharmacy services like the one described should be implemented widely to increase patient safety.

PMID:35033079 | DOI:10.1186/s12913-022-07494-5

Medicine (Baltimore). 2022 Jan 14;101(2):e28561. doi: 10.1097/MD.0000000000028561.

ABSTRACT

The COVID-19 pandemic, caused by the SARS-CoV2 virus, has infected millions worldwide with cancer patients demonstrating a higher prevalence for severe disease and poorer outcomes. Recently, the BNT162b2 mRNA COVID-19 vaccine was released as the primary means to combat COVID-19. The currently reported incidence of local and systemic side effects was 27% in the general public. The safety of the BNT162b2 mRNA COVID-19 vaccine has not been studied in patients with an active cancer diagnosis who are either ongoing or plan to undergo oncologic therapy.This single center study reviewed the charts of 210 patients with active cancer diagnoses that received both doses of the BNT162b2 mRNA COVID-19 vaccine. The development of side effects from the vaccine, hospitalizations or exacerbations from various oncologic treatment were documented. Type of oncologic treatment (immunotherapy, chemotherapy, hormonal, biologic, radiation or mixed) was documented to identify if side effects were related to treatment type. The time at which the vaccine was administered in relation to treatment onset (on long term therapy, within 1 month of therapy or prior to therapy) was also documented to identify any relationships.Sixty five (31%) participants experienced side effects from the BNT162b2 mRNA COVID-19 vaccine, however most were mild to moderate. Treatment protocol was not linked to the development of vaccine related side effects (P = .202), nor was immunotherapy (P = .942). The timing of vaccine administered in relation to treatment onset was also not related to vaccine related side effects (P = .653). Six (2.9%) participants were hospitalized and 4 (2%) died.The incidence of side effects in cancer patients is similar to what has been reported for the general public (31% vs 27%). Therefore, we believe that the BNT162b2 mRNA COVID-19 vaccine is safe in oncologic patients undergoing numerous cancer treatments.

PMID:35029223 | PMC:PMC8758044 | DOI:10.1097/MD.0000000000028561

Bioorg Chem. 2022 Jan 7;120:105599. doi: 10.1016/j.bioorg.2022.105599. Online ahead of print.

ABSTRACT

Doxorubicin belongs to the anthracycline chemical class of the drug and is one of the widely used anticancer drugs. The common side effects of doxorubicin include vomiting, hair loss, rashes to serious side-effects such as irreversible cardiotoxicity, and drug-induced leukemia. This led many researchers around the globe to develop methods aimed to achieve higher efficacy and lower toxicity for doxorubicin. The present review article provides a detailed account of the design strategies i.e., chemical modifications and conjugate formation adopted by various research groups to minimize the side effects without compromising with the significant anticancer profile of the drug doxorubicin. Chemical modification of the drug includes alteration at C4' hydroxyl and C3' amine groups present in the sugar part. The pH-sensitive drug delivery system is covered highlighting use of theranostic tantalum oxide to the traditional approach of conjugating with acyl hydrazine and thiourea. Methods adopted to increase the bioavailability of the drugs inside the cancer cells viz., conjugation with humanized monoclonal antibody and other peptides along with their promising results are also discussed. The review further discusses works from recent years comprising of different nanoforms of doxorubicin for the targeted delivery of drugs inside the tumor cells. Few of the articles targeting nucleus or mitochondria as one of the effective cancer treatments are reported. The brain is inaccessible to the drug and it was modified through galactoxyloglucan-modified gold nanocarrier or conjugated with lactoferrin with enhanced permeability through the blood-brain barrier. Prodrug has particularly been used to target tumor tissues without affecting other tissue organs. The present review article offer clear advantages of one method over another adopted to target the cancer cells and may provide an insight for the researchers working in this area.

PMID:35030480 | DOI:10.1016/j.bioorg.2022.105599

Turk J Pediatr. 2021;63(6):941-954. doi: 10.24953/turkjped.2021.06.001.

ABSTRACT

BACKGROUND: Vaccination is one of the most effective public health tools to prevent a variety of infectious diseases. However, concerns about vaccine related adverse effects cause difficulties in clinical practice.

METHODS: This review was prepared based on the latest literature available in the PUBMED database in English language (as of March 2021), and all articles with the keywords pediatric vaccine, allergy, hypersensitivity, adverse reaction were evaluated to prepare the article.

RESULTS: Vaccine related confirmed allergic reactions are rare in children, ranging between 0,65-1.45 cases per million vaccine doses. Most of the allergic reactions are self-limited local reactions although in some cases severe anaphylaxis with multisystem involvement can be observed. Allergic reactions may occur because of either the active component (the antigen) of the vaccine, or additional components, such as preservatives, adjuvants, antimicrobials, stabilizers and other substances. Finding the culprit allergen is necessary to prevent future exposure to the allergen and to use alternative vaccines if possible. Diagnosis is largely based on a detailed history and clinical manifestation; also in vivo and in vitro tests may be helpful.

CONCLUSIONS: In this review we provide information about hypersensitivity reactions to allergen components of childhood vaccines along with the diagnosis and management of vaccine allergy. Besides the tremendous benefits of vaccination for the health of children, we emphasized that the risk of adverse effects is rare and poses a negligible threat.

PMID:35023644 | DOI:10.24953/turkjped.2021.06.001

Clin Microbiol Infect. 2022 Jan 10:S1198-743X(21)00734-5. doi: 10.1016/j.cmi.2021.12.026. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate whether favipiravir reduces the time to viral clearance as documented by negative SARS-CoV-2 RT-PCR in mild COVID-19 cases compared to placebo.

METHODS: In this randomized, double-blinded, multicenter, and placebo-controlled trial, adults with PCR confirmed mild COVID-19 were recruited in an outpatient setting at seven medical facilities across Saudi Arabia. Participants were randomized in a 1:1 ratio to receive either favipiravir 1800 mg by mouth twice daily on day one followed by 800 mg twice daily (n=112) or a matching placebo (n=119), for a total of 5 to 7 days. The primary outcome was the effect of favipiravir on reducing the time to viral clearance (by PCR test) within 15 days of starting the treatment compared to the placebo group. The trial included the following secondary outcomes: symptom resolution, hospitalization, ICU admissions, adverse events, and 28-day mortality.

RESULTS: 231 patients were randomized and began the study (median age, 37 [interquartile range: 32-44] years; 155 [67%] men), and 112 (48.5%) were assigned to the treatment group and 119 (51.5%) into the placebo group. The data and safety monitoring board (DSMB) recommended stopping enrollment because of futility at the interim analysis. The median time to viral clearance was 10 (IQR: 6-12) days in the favipiravir group and 8 (IQR: 6-12) days in the placebo group, with a hazard ratio of 0.87 for the favipiravir group (95% CI 0.571 to 1.326; p-value =0.51). The median time to clinical recovery was 7 days (IQR: 4-11) in the favipiravir group and 7 days (IQR: 5-10) in the placebo group. There was no difference between the two groups on the secondary outcome of hospital admission. There were no drug-related severe adverse events.

CONCLUSION: In this clinical trial, favipiravir therapy in mild COVID-19 patients did not reduce the time to viral clearance within 15 days of starting the treatment.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier (NCT04464408): https://clinicaltrials.gov/ct2/show/NCT04464408.

PMID:35026375 | DOI:10.1016/j.cmi.2021.12.026

Target Oncol. 2022 Jan 13. doi: 10.1007/s11523-021-00865-8. Online ahead of print.

ABSTRACT

BACKGROUND: The development of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) has improved the survival outcomes of patients with advanced ALK-rearranged non-small-cell lung cancer (NSCLC). The adverse events (AEs) related to ALK inhibitors are fairly well known; notably, about 20% of patients receiving lorlatinib experienced cognitive effects and behavioral alterations in pivotal trials. Therefore, psychiatric disorders could represent AEs of special interest for all ALK TKIs, deserving careful assessment in the post-marketing setting.

OBJECTIVE: We conducted a real-world pharmacovigilance study on psychiatric AEs with marketed ALK inhibitors in subjects with advanced NSCLC.

PATIENTS AND METHODS: We performed an observational, retrospective analysis of spontaneous reports submitted to the Food and Drug Administration Adverse Events Reporting System (FAERS, as of December 2020), selecting psychiatric AEs to ALK TKIs approved in NSCLC (crizotinib, ceritinib, alectinib, brigatinib, lorlatinib). These AEs were independently scrutinized by three oncologists applying predefined exclusion criteria, described in terms of clinical/demographic features and assessed for drug-related causality according to an adaptation of the WHO-UMC system, a standardized probabilistic algorithm.

RESULTS: Among 584 reported psychiatric AEs, 95 cases were selected as potentially treatment related, with higher reporting frequency for lorlatinib (26, 2.8%), followed by brigatinib (10, 1.2%), alectinib (18, 0.7%), ceritinib (12, 0.6%), and crizotinib (29, 0.3%). Reported psychiatric symptoms were mood disorders (39), psychotic disorders (24), and anxiety, agitation, and irritability (25). In the majority (74%) of cases, psychiatric AEs were serious and required hospitalization in about 32% of patients; 15.8% of retained cases were considered as highly probable and 69.5% as probable. Drug discontinuation was recorded in 31.6% of the reported cases, with the highest proportion for lorlatinib (65.4%).

CONCLUSION: Notwithstanding limitations, our study found a higher proportion of psychiatric AEs with lorlatinib, but also raised the hypothesis of psychiatric reactions as a class effect of ALK TKIs.

PMID:35025076 | DOI:10.1007/s11523-021-00865-8

Int J Womens Dermatol. 2021 Sep 28;7(5Part A):615-624. doi: 10.1016/j.ijwd.2021.09.009. eCollection 2021 Dec.

ABSTRACT

With the development of molecular targeted therapies, a wide array of dermatologic toxicities is appearing. Their prevention, recognition, and management by dermatologists is critical to ensure antineoplastic treatment continuation. The objective of this study was to provide a literature review of the most common dermatologic toxicities due to targeted therapies in oncologic patients, including their clinical presentation, prevention, and management.

PMID:35024416 | PMC:PMC8721134 | DOI:10.1016/j.ijwd.2021.09.009

Turk J Pediatr. 2021;63(6):970-977. doi: 10.24953/turkjped.2021.06.004.

ABSTRACT

BACKGROUND: Medication errors are frequently seen in pediatric patients. Medication error studies on pediatric cases were found to not only be limited but also the collaboration of clinical pharmacists and physicians on this topic was not published in Turkey. This study aimed to identify drug-related problems, especially in antibiotics.

METHODS: This study was a point prevalence study with pediatric inpatients that used at least one antibiotic at a pediatric tertiary care reference hospital on November 16, 2016. Medications of patients were evaluated by clinical pharmacists in terms of drug-related problems and by physicians in terms of correct indications.

RESULTS: Eighty-nine hospitalized patients were using antibiotics at the time of the study. The median age was 42 months (range: 1-226 months), and 49 (55.1%) of the patients were male. Clinical pharmacists detected a total of 210 potential drug-drug interactions in 46 (51.7%) patients. Approximately 48.5% of the patients in pediatric wards and 52.4% of the patients in surgical wards had at least one potential drug-drug interaction. A total of 39 medication errors were identified in 36 patients` drug orders. Most of the errors (51.3%) were due to dosing and administration time errors (35.9%). The number of errors per patient in surgical services was higher (0.47) than the pediatric services (0.42). Forty-three percent of errors were antimicrobial-related, and 70.5% of them were classified as dosing errors.

CONCLUSIONS: Evaluation of patients` drug usage by a clinical pharmacist in terms of drug-related problems such as drug interactions, side effects and prescribing errors leads to better pharmaceutical care.

PMID:35023646 | DOI:10.24953/turkjped.2021.06.004