Anticancer Res. 2022 Jul;42(7):3575-3582. doi: 10.21873/anticanres.15844.

ABSTRACT

BACKGROUND/AIM: Durvalumab is a human monoclonal antibody targeting programmed cell death ligand 1. It is classified as an immune checkpoint inhibitor and has shown high efficacy as maintenance therapy after chemoradiation for stage III non-small-cell lung cancer and as the primary treatment for small-cell carcinoma. Interstitial lung disease is the most common adverse event leading to durvalumab discontinuation. Hence, this study was aimed at assessing the incidence and timing of durvalumab-induced lung toxicity by using the Japanese Adverse Drug Event Report (JADER) database.

PATIENTS AND METHODS: Adverse Adverse events (AEs) of durvalumab reported from August 2018 to March 2021 were extracted. Data on lung AEs were analysed to estimate relative risk using reporting odds ratios (RORs) and 95% confidence interval (CIs). Furthermore, the times of onset of signs of lung toxicity were also estimated.

RESULTS: Overall, 2,162 AEs attributable to durvalumab were obtained. Of these, 1,239 were lung toxicities, the most common among which were pneumonia, interstitial lung disease, and radiation-associated pneumonitis. The corresponding RORs (95% CIs) for these signs were 271.50 (244.79-301.11), 5.96 (5.29-6.72), and 713.21 (595.04-854.85), respectively. The median (interquartile range) times of onset were 32.5 (28.5-35.5), 31.5 (28.5-41.5), and 28.5 (28.5-30.5) days, respectively.

CONCLUSION: Among the AEs of durvalumab, pneumonia, interstitial lung disease, and radiation-induced pneumonitis were associated with high RORs, suggesting a strong causal relationship with durvalumab. Interstitial lung disease and radiation-induced pneumonitis most often occurred approximately 30 days after treatment initiation, suggesting that monitoring for adverse events during this period is important.

PMID:35790278 | DOI:10.21873/anticanres.15844

Anticancer Res. 2022 Jul;42(7):3693-3700. doi: 10.21873/anticanres.15858.

ABSTRACT

BACKGROUND/AIM: Eribulin is an effective chemotherapeutic agent for the treatment of metastatic breast cancer and advanced or metastatic soft-tissue sarcomas. However, severe adverse effects (SAEs) occur in 30-40% of the patients, and significantly reduce the patients' quality of life and disturb the recommended treatment schedules. Neutropenia is the main cause of treatment suspension, delay, and/or dose reductions, also leading to relative dose intensity reduction. This study aimed to examine the risk factors for SAE occurrence after eribulin treatment.

PATIENTS AND METHODS: Eighty patients with metastatic breast cancer or advanced or metastatic soft tissue sarcoma who received eribulin were retrospectively evaluated. Risk factors for SAE occurrence in the first cycle were primarily assessed. In addition, factors associated with SAE occurrence during all treatment cycles were evaluated.

RESULTS: SAEs in the first cycle occurred in 45% of patients. The primary SAE was neutropenia (91.7%). The incidence of SAEs during all treatment cycles was 61.3%. Multivariate analyses suggested that lower baseline neutrophil and hemoglobin levels were risk factors for SAE occurrence and severe neutropenia incidence in the first cycle. An independent factor associated with SAE occurrence during all cycles was age ≥65 years and a tendency was confirmed for baseline anemia.

CONCLUSION: Baseline neutropenia and anemia were risk factors for SAE occurrence during the first eribulin treatment cycle. Age ≥65 years was also associated with SAE occurrence during all treatment cycles. Patients with these risk factors should be carefully monitored for assessment and prophylaxis.

PMID:35790277 | DOI:10.21873/anticanres.15858

BMJ Open. 2022 Jul 4;12(7):e055551. doi: 10.1136/bmjopen-2021-055551.

ABSTRACT

OBJECTIVE: To ascertain the burden and associated cost of adverse drug reactions (ADRs), polypharmacy and multimorbidity through a prospective analysis of all medical admissions to a large university teaching hospital over a 1-month period.

DESIGN: Prospective observational study.

SETTING: Liverpool University Hospital Foundation National Health Service (NHS) Trust, England.

PARTICIPANTS: All medical admissions with greater than 24-hour stay over a 1-month period.

MAIN OUTCOME MEASURES: Prevalence of admissions due to an ADR and associated mortality, prevalence and association of multimorbidity and polypharmacy with ADRs, and estimated local financial cost of admissions where an ADR was a contributing or main reason for admission with projected costs for NHS in England.

RESULTS: There were 218 identified patient admissions with an ADR giving a prevalence of 18.4%. The majority of these (90.4%) were ADRs that directly resulted in or contributed to admission. ADRs thus accounted for 16.5% of total admissions. Those with an ADR were on average taking more medicines (10.5 vs 7.8, p<0.01) and had more comorbidities than those without an ADR (6.1 vs 5.2, p<0.01). Drugs most commonly implicated were diuretics, steroid inhalers, anticoagulants and antiplatelets, proton pump inhibitors, chemotherapeutic agents and antihypertensives. 40.4% of ADRs were classified avoidable or possibly avoidable. The mortality rate due to an ADR was 0.34%. The average length of stay for those with an ADR was 6 days. Direct 1-month cost to the Trust from ADR admissions was £490 716. Extrapolated nationally, the projected annual cost to the NHS in England is 2.21 billion.

CONCLUSION: The local prevalence of admission and mortality from ADRs is higher than previously reported. Important factors that could be contributing to this include polypharmacy and multimorbidity. ADRs place a significant burden on patients and healthcare services with associated financial implications. Reducing inappropriate polypharmacy should be a major aim for preventing ADRs.

PMID:35788071 | DOI:10.1136/bmjopen-2021-055551

BMJ Case Rep. 2022 Jul 4;15(7):e251173. doi: 10.1136/bcr-2022-251173.

ABSTRACT

Carfilzomib is a selective proteosome inhibitor that is commonly used in the treatment of relapsed or refractory multiple myeloma. Carfilzomib has been commonly associated with respiratory side effects. It can rarely also cause fatal pulmonary toxicity. We present a case of a man in his 50s with plasma cell leukaemia who was initiated on treatment with carfilzomib and dexamethasone. He developed severe pneumonitis requiring oxygen via a high-flow nasal cannula. After an extensive workup, a temporal relationship between the carfilzomib use and exacerbation of the pulmonary symptoms was found. Carfilzomib was permanently discontinued, and the patient was started promptly on methyl prednisolone with complete resolution of his symptoms. Due to the associated risk of mortality if not detected early, we wish to highlight this rare but serious pulmonary toxicity associated with carfilzomib that was managed with high-dose glucocorticoids.

PMID:35787495 | DOI:10.1136/bcr-2022-251173

Yakugaku Zasshi. 2022;142(7):771-774. doi: 10.1248/yakushi.21-00237.

ABSTRACT

We report a haemodialysis patient with end-stage renal failure whom a pharmacist aided in the management of acyclovir (ACV) encephalopathy, which may have been related to valacyclovir hydrochloride (VACV) administered without sufficient dose reduction. The patient 78 years was admitted with a tentative diagnosis of varicella zoster viral meningitis. A pharmacist suspected ACV encephalopathy related to excessive VACV administration and raised a query with the attending physician. According to the pharmacist's proposal, ACV administration was discontinued and continuous hemodiafiltration (CHDF) was performed. On day 5 of hospitalisation, the consciousness disorder was improved. In this report, we showed the detailed CHDF conditions of the present case, and the contribution of a pharmacist to treating and avoiding ACV encephalopathy was discussed.

PMID:35781507 | DOI:10.1248/yakushi.21-00237

Drug Saf. 2022 Jul 5. doi: 10.1007/s40264-022-01204-0. Online ahead of print.

ABSTRACT

Adverse drug reactions (ADRs) affecting the pancreas are a heterogeneous group of side effects that cause damage to pancreatic cells. Various mechanisms such as hypersensitization, sphincter of Oddi constriction, direct cytotoxic and metabolic effects on pancreatic cells, and dose-dependent idiosyncrasy lead to intrapancreatic activation of pancreatic enzymes resulting in drug-induced acute pancreatitis. Several medications have been linked with the development of pancreatic cancer. Pancreatic cancer may result from proinflammatory, proliferative, and antiapoptotic effects. Diabetogenic effect of drugs, which is understood as impairment of insulin secretion, may occur due to direct destruction of β cells, systemic toxicity affecting pancreatic islets and cell membrane glucose transporters, induction of Th1-type autoimmune response, and impairment of voltage-gated calcium channels in β cells, endoplasmic reticulum stress, and insulin signaling. A better understanding of ADRs that affect the pancreas may contribute to improving the awareness of clinicians and patients and reducing potential harmful side effects of implemented therapies.

PMID:35788538 | DOI:10.1007/s40264-022-01204-0

Cureus. 2022 Jun 1;14(6):e25557. doi: 10.7759/cureus.25557. eCollection 2022 Jun.

ABSTRACT

Pulmonary tuberculosis (TB) is highly prevalent in Pakistan, and immunosuppressed individuals (including those on long-term corticosteroid therapy) are at an especially high risk of infection. Owing to the limited number of effective antituberculous drugs, treating resistant cases or patients who develop unfavorable side effects from the first-line agents becomes a daunting task. We discuss a patient with congenital adrenal hyperplasia (CAH) suffering from pulmonary TB who developed drug-induced hepatitis after being started on recommended first-line anti-TB drugs.

PMID:35785003 | PMC:PMC9249006 | DOI:10.7759/cureus.25557

Hepatol Forum. 2021 Sep 15;2(3):122-127. doi: 10.14744/hf.2021.2021.0020. eCollection 2021 Sep.

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of coronavirus disease 2019 (COVID-19), is highly contagious and has a variety of clinical manifestations, including liver injury. There have been a few reports indicating acute-on chronic liver failure among COVID-19 patients, however, patients with COVID-19-related liver injury are generally asymptomatic and present with a mild to moderate elevation in serum hepatic enzymes. Severe COVID-19 patients have high rates of liver injury with poorer outcomes. The pattern of abnormalities in liver biochemical indicators may be hepatocellular, cholestatic, or mixed. Although the pathogenesis of hepatic injury is not yet completely understood, causes of liver damage include systemic inflammatory response syndrome, ischemia-reperfusion injury, side effects of medications, and underlying chronic liver disease. While viral RNA has been detected in hepatocytes, it remains unknown if the coronavirus has the capacity to cause cytopathic effects in hepatic tissue. Additionally, it is important to remember that the current upheaval to daily life and access to healthcare caused by the COVID-19 pandemic has had a significant and negative effect on other patients with chronic liver disease. The objective of this review was to summarize the current literature on COVID-19-related hepatic injury with an examination of clinical features, potential pathogenesis, and histopathological findings of this entity.

PMID:35784909 | PMC:PMC9138946 | DOI:10.14744/hf.2021.2021.0020

Front Pharmacol. 2022 Jun 15;13:893166. doi: 10.3389/fphar.2022.893166. eCollection 2022.

ABSTRACT

Background: This study was conducted to explore the safety, tolerance, pharmacokinetics, pharmacodynamics, and immunogenicity of LY06006, a recombinant humanized monoclonal antibody to RANKL, when administrated subcutaneously in Chinese healthy adults. Research design and methods: This was a randomized, double-blinded, placebo-controlled, single ascending dose study performed in 32 healthy Chinese adults, who were randomly assigned to receive a single injection dose of 18, 60, 120 mg study drug or placebo with a follow-up of 140-252 days. Results: No deaths or drug-related serious adverse events occurred. LY06006 was rapidly absorbed in the 60 mg group with a Tmax range of 120-480 h and serum LY06006 concentrations decreased slowly 11-13 days after dosing with a long mean (SD) half-life of 389.58 (63.44) h. The most frequent AEs were elevated serum parathyroid hormone (PTH) level (83.3%), hypocalcemia (54.2%), and hypophosphatemia (45.8%). None of the 32 subjects tested positive for anti-drug antibody during the trial. Conclusion: Single-dose subcutaneous administration of LY06006 was safe and well-tolerated in healthy Chinese adults. Cmax showed linear pharmacokinetic characteristics in the dose range of 18-120 mg based on dose-exposure proportionality analysis.

PMID:35784742 | PMC:PMC9240259 | DOI:10.3389/fphar.2022.893166

Infect Drug Resist. 2022 Jun 25;15:3323-3332. doi: 10.2147/IDR.S369368. eCollection 2022.

ABSTRACT

OBJECTIVE: There are few therapeutic options for infections caused by carbapenem-resistant Enterobacterales (CRE) in children following liver transplantation. Ceftazidime-avibactam (CAZ-AVI), a recently licensed antibacterial in China, was utilized as a salvage therapy against CRE in our center, and its efficacy and safety were therefore assessed.

METHODS: The retrospective, observational study was conducted at the First Affiliated Hospital of Zhejiang University. Pediatric liver transplantation patients (≤12 years) who received CAZ-AVI as a salvage therapy against CRE infections were included from January 2020 to December 2021. Clinical success and all-cause death during hospitalization were the primary outcomes. Recurrence of infection, drug-related adverse events, and changes in inflammatory biomarkers were collected.

RESULTS: Six children were enrolled, with a median age of 10.1 (interquartile range (IQR) 5.5-13.8) months. Primary intraperitoneal infections occurred in all patients, with five patients developing bloodstream infections. KPC carbapenemases were detected in most isolates, and the susceptibility results showed general sensitivity to tigecycline, polymyxin B, and CAZ-AVI. Tigecycline-based therapy was taken as the initial treatment and withdrawn because of clinical failure (5 cases) or cholestasis (1 case). After CRE infection, the median time to convert to CAZ-AVI was 7.5 (IQR 7.0-8.8) days, and the median CAZ-AVI treatment length was 21.0 (IQR 20.3-28.5) days. Clinical success was achieved in all patients, with a zero percent all-cause death rate. No CRE infections recurred throughout hospitalization, and no resistance to CAZ-AVI was detected. Patients experienced vomiting (1/6), skin rash (1/6), and a transient increase in cystatin C (2/6), γ-glutamyltransferase (2/6), and alkaline phosphatase (3/6).

CONCLUSION: CAZ-AVI was shown to be a successful salvage treatment for CRE infection in pediatric liver transplant recipients, with minor and temporary drug-related side effects.

PMID:35782529 | PMC:PMC9241992 | DOI:10.2147/IDR.S369368

Med J Aust. 2022 Jul 4. doi: 10.5694/mja2.51619. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the short term safety of the COVID-19 vaccines Comirnaty (Pfizer-BioNTech BNT162b2) and Vaxzevria (AstraZeneca ChAdOx1) in Australia.

DESIGN: Prospective observational cohort study; online surveys by AusVaxSafety, a national active vaccine safety surveillance system, three and eight days after vaccination.

SETTING, PARTICIPANTS: People aged 16 years or more who received COVID-19 vaccines at sentinel vaccination hubs, general practices, or Aboriginal Community Controlled Health Organisation clinics, 22 February - 30 August 2021.

MAIN OUTCOME MEASURES: Primary outcome: proportion of respondents who reported any adverse event following immunisation (AEFI) 0-3 days after vaccination.

SECONDARY OUTCOMES: proportions of respondents who reported specific adverse events or medical review for AEFI within seven days of vaccination; impact on usual daily activities; recovery.

RESULTS: 4 851 480 people received COVID-19 vaccines at participating sentinel sites during the study period (25% of all COVID-19 vaccine doses administered in Australia to 30 August 2021). 3 035 983 people responded to both surveys (response rate, 62.6%); 35.9% of respondents reported one or more AEFI 0-3 days after Comirnaty dose 1, 54.7% after Comirnaty dose 2, 52.8% after Vaxzevria dose 1, and 22.0% after Vaxzevria dose 2. Local pain, fatigue, headache, and myalgia were the most frequently reported symptoms. After adjusting for demographic characteristics, vaccination site type, jurisdiction, and self-reported medical conditions, the odds of reporting any AEFI were higher for women than men (range of adjusted odd ratios [aORs], by vaccine and dose, 1.53-1.84), for people with a history of anaphylaxis (aOR range, 1.28-1.45), and for people reporting certain underlying conditions, including obesity (aOR range, 1.15-1.75), immunodeficiency (aOR range, 1.04-2.24), or chronic inflammatory disease (aOR range, 1.05-1.75). 0.9% of respondents sought medical advice in the three days following vaccination, most frequently after Comirnaty dose 2 (1.4%) and Vaxzevria dose 1 (1.2%).

CONCLUSION: AusVaxSafety active surveillance affirms the short term safety profile of Comirnaty and Vaxzevria vaccines in a large population sample during the first six months of the Australian COVID-19 vaccination program.

PMID:35781813 | DOI:10.5694/mja2.51619

Adv Cancer Res. 2022;155:77-129. doi: 10.1016/bs.acr.2022.03.005. Epub 2022 Apr 26.

ABSTRACT

It has been estimated that nearly 80% of anticancer drug-treated patients receive potentially nephrotoxic drugs, while the kidneys play a central role in the excretion of anticancer drugs. Nephrotoxicity has long been a serious complication that hampers the effectiveness of cancer treatment and continues to influence both mortality and length of hospitalization among cancer patients exposed to either conventional cytotoxic agents or targeted therapies. Kidney injury arising from anticancer drugs tends to be associated with preexisting comorbidities, advanced cancer stage, and the use of concomitant non-chemotherapeutic nephrotoxic drugs. Despite the prevalence and impact of kidney injury on therapeutic outcomes, the field is sorely lacking in an understanding of the mechanisms driving cancer drug-induced renal pathophysiology, resulting in quite limited and largely ineffective management of anticancer drug-induced nephrotoxicity. Consequently, there is a clear imperative for understanding the basis for nephrotoxic manifestations of anticancer agents for the successful management of kidney injury by these drugs. This article provides an overview of current preclinical research on the nephrotoxicity of cancer treatments and highlights prospective approaches to mitigate cancer therapy-related renal toxicity.

PMID:35779877 | DOI:10.1016/bs.acr.2022.03.005

Adv Cancer Res. 2022;155:215-244. doi: 10.1016/bs.acr.2022.02.006. Epub 2022 Mar 21.

ABSTRACT

Cancer therapeutics are dynamically evolving, and include traditional chemotherapy and hormone therapy, as well as more recently developed treatment modalities, such as tyrosine kinase inhibitors, monoclonal antibodies and the revolutionary approach based on immune checkpoint inhibition. These regimens are unfortunately not free of adverse events, and patients with cancer are a susceptible population experiencing a myriad of disease and treatment toxicities combined. In this review, we present the latest overview of the management of the most common systemic cancer treatment symptoms and the science of symptom management supporting these strategies. We discuss cancer-related cognitive impairment, ocular toxicity, ototoxicity, oral mucosal toxicities, gastrointestinal toxicities, renal toxicity, aromatase inhibitor-induced musculoskeletal symptoms, chemotherapy-induced peripheral neuropathy, and immunotherapy-induced autoimmunity derived from systemic therapies for cancer. In summary, we review the future directions and ideal goals of symptom science research in order to benefit patients utilizing a comprehensive individualized approach.

PMID:35779875 | DOI:10.1016/bs.acr.2022.02.006

Curr Opin Ophthalmol. 2022 Jul 1;33(4):311-317. doi: 10.1097/ICU.0000000000000860.

ABSTRACT

PURPOSE OF REVIEW: The purpose of this review is to give an overview of the corneal manifestations of targeted systemic immunotherapies and provide guidelines for management when applicable.

RECENT FINDINGS: The advent of newer systemic immunosuppressive therapy has resulted in the need for more awareness of potential ocular side effects. Side effects can range from vortex keratopathy as seen with the tyrosine kinase inhibitors, to epithelial microcysts as reported in the use of cytarabine and belantamab mafodotin, spontaneous corneal perforations have been reported with programmed death 1 inhibitors, while eyelid cicatrization has been reported epidermal growth factor inhibitors. Several immunomodulatory therapies result in conjunctivitis which tends to respond to topical lubrication and corticosteroid treatment. Most manifestations listed in the review are limited to the anterior segment; however, some may lead to retinal and optic nerve changes which can be permanently damaging.

SUMMARY: Ocular surface and corneal changes secondary to systemic immunosuppression can affect main components of the ocular surface. Although most adverse effects are reversible, few changes can be permanent and therefore close ophthalmologic monitoring is necessary.

PMID:35779055 | DOI:10.1097/ICU.0000000000000860

Neurol Ther. 2022 Jul 2. doi: 10.1007/s40120-022-00380-6. Online ahead of print.

ABSTRACT

INTRODUCTION: This randomized, double-blind, placebo-controlled study in healthy volunteers assessed the safety, tolerability, and pharmacokinetics of single ascending doses of intravenously administered NX210-a linear peptide derived from subcommissural organ-spondin-and explored the effects on blood/urine biomarkers and cerebral activity.

METHODS: Participants in five cohorts (n = 8 each) were randomized to receive a single intravenous dose of NX210 (n = 6 each) (0.4, 1.25, 2.5, 5, and 10 mg/kg) or placebo (n = 2 each); in total, 10 and 29 participants received placebo and NX210, respectively. Blood samples were collected for pharmacokinetics within 180 min post dosing. Plasma and urine were collected from participants (cohorts: 2.5, 5, and 10 mg/kg) for biomarker analysis and electroencephalography (EEG) recordings within 48 h post dosing. Safety/tolerability and pharmacokinetic data were assessed before ascending to the next dose.

RESULTS: The study included 39 participants. All dosages were safe and well tolerated. All treatment-emergent adverse events (n = 17) were of mild severity and resolved spontaneously (except one with unknown outcome). Twelve treatment-emergent adverse events (70.6%) were deemed drug related; seven of those (58.3%) concerned nervous system disorders (dizziness, headache, and somnolence). The pharmacokinetic analysis indicated a short half-life in plasma (6-20 min), high apparent volume of distribution (1870-4120 L), and rapid clearance (7440-16,400 L/h). In plasma, tryptophan and homocysteine showed dose-related increase and decrease, respectively. No drug dose effect was found for the glutamate or glutamine plasma biomarkers. Nevertheless, decreased blood glutamate and increased glutamine were observed in participants treated with NX210 versus placebo. EEG showed a statistically significant decrease in beta and gamma bands and a dose-dependent increasing trend in alpha bands. Pharmacodynamics effects were sustained for several hours (plasma) or 48 h (urine and EEG).

CONCLUSION: NX210 is safe and well tolerated and may exert beneficial effects on the central nervous system, particularly in terms of cognitive processing.

PMID:35779189 | DOI:10.1007/s40120-022-00380-6

Dermatol Ther. 2022 Jul 2:e15683. doi: 10.1111/dth.15683. Online ahead of print.

ABSTRACT

BACKGROUND: Gel formulation of chlormethine (CG) has gained a preeminent role among therapies available for mycosis fungoides (MF).

OBJECTIVES: To evaluate the frequency of use of CG for MF treatment and to determine the limits and potentialities of CG in a real-world setting.

MATERIALS AND METHODS: A systematic review of articles published prior to October 2021 was performed. Articles were included in the review if a full-text English version was available. MEDLINE (PubMed), Scopus and Web of Science were each queried from their date of inception with the following terms: "mechlorethamine gel", "chlormethine gel" and "mycosis fungoides". The reference lists of the studies retrieved were searched manually. Moreover, this study included all consecutive patients with different stages of MF (from IA to IIB) who started treatment with CG gel between July 2020 and May 2021. Data of the literature were compared to our single-center real-life experience.

RESULTS: Of the surveyed literature, 11 publications were included in the final analysis describing a total of 548 patients with MF. 11 patients with a median (standard deviation) age of 66 years (15.1) were enrolled and followed up, receiving CG (0.02% chlormethine HCl). Response to treatment resulted higher (90.1%) in our study population than in other real-world experiences published in literature.

CONCLUSION: This systematic review supports the role of CG for MF treatment, showing its limits and potentialities. Our single-center real-life experience revealed an elevated percentage of clinical response with high safety and tolerance, demonstrating its versatile use with dose and application rate adaptability.

PMID:35778940 | DOI:10.1111/dth.15683

BMJ Open. 2022 Jul 1;12(7):e061725. doi: 10.1136/bmjopen-2022-061725.

ABSTRACT

INTRODUCTION: Combination antiretroviral therapy (cART) has massively reduced HIV mortality. However, long-term cART increases the risk of adverse drug reactions (ADRs), which can lead to higher morbidity, mortality and healthcare costs for people living with HIV (PLHIV).Pharmacovigilance-monitoring the effects of medicines-is essential for understanding real-world drug safety. In Uganda, pharmacovigilance systems have only recently been developed, and rates of ADR reporting for cART are very low. Thus, the safety profile of medicines currently used to treat HIV and tuberculosis in our population is poorly understood.The Med Safety mobile application has been developed through the European Union's Innovative Medicines Initiative WEB-Recognising Adverse Drug Reactions project to promote digital pharmacovigilance. This mobile application has been approved for ADR-reporting by Uganda's National Drug Authority. However, the barriers and facilitators to Med Safety uptake, and its effectiveness in improving pharmacovigilance, are as yet unknown.

METHODS AND ANALYSIS: A pragmatic cluster-randomised controlled trial will be implemented over 30 months at 191 intervention and 191 comparison cART sites to evaluate Med Safety. Using a randomisation sequence generated by the sealed envelope software, we shall randomly assign the 382 prescreened cART sites to the intervention and comparison arms. Each cART site is a cluster that consists of healthcare professionals and PLHIV receiving dolutegravir-based cART and/or isoniazid preventive therapy. Healthcare professionals enrolled in the intervention arm will be trained in the use of mobile-based, paper-based and web-based reporting, while those in the comparison arm will be trained in paper-based and web-based reporting only.

ETHICS AND DISSEMINATION: Ethical approval was given by the School of Biomedical Sciences Research and Ethics Committee at Makerere University (SBS-REC-720), and administrative clearance was obtained from Uganda National Council for Science and Technology (HS1366ES). Study results will be shared with healthcare professionals, policymakers, the public and academia.

TRIAL REGISTRATION NUMBER: PACTR202009822379650.

PMID:35777873 | PMC:PMC9252195 | DOI:10.1136/bmjopen-2022-061725

Age Ageing. 2022 Jul 1;51(7):afac138. doi: 10.1093/ageing/afac138.

ABSTRACT

Prescribing cascades are increasingly recognized since they were described in the mid-1990s. Cascades are more likely in older people with multimorbidity and associated polypharmacy where multiple medications can induce a variety of side effects that manifest with various non-specific symptoms that may be misidentified as new geriatric syndromes such as falls, dizziness and new-onset incontinence. Geriatricians encounter medication side effects frequently and will usually consider if an older patient presenting with new symptoms could be experiencing an adverse drug reaction or event. However, most medications prescribed to multimorbid older patients are initiated and continued by prescribers without specialist geriatric training who may not detect medication-induced morbidity. Therefore, novel approaches to the detection and management of prescribing cascades in older people are needed. Currently, the knowledge base surrounding prescribing cascades in older people is evolving towards better methods for cascade detection and secondary prevention. However, the large number of cascades described in the literature, the wide-ranging symptomatology of cascades and the rapidly increasing number of multimorbid older people at risk of cascades represent major challenges for prescribers. Furthermore, prospective prevalence studies of prescribing cascades in older people are lacking. To detect and correct prescribing cascades during routine medication review in multimorbid older people, awareness of cascades is essential. Prescribing cascade awareness in turn requires novel explicit ways of defining cascades to facilitate their rapid detection and correction during medication review. Given that prescribing cascades represent another aspect of inappropriate prescribing (IP), explicit cascades criteria should be integrated with other explicit IP criteria.

PMID:35776668 | DOI:10.1093/ageing/afac138

Eur J Case Rep Intern Med. 2022 May 13;9(5):003380. doi: 10.12890/2022_003380. eCollection 2022.

ABSTRACT

Prothrombin time (PT), first used in 1935, is the most commonly employed marker of coagulopathy to assess bleeding tendency. It is a screening test and measures the time in seconds to the formation of a clot after platelet-poor plasma has been mixed with a thromboplastin reagent consisting of tissue factor, lipids and calcium chloride ions. The International Normalized Ratio (INR) is a standardized number based on the PT of the patient. It is used by clinicians to measure the effectiveness of anticoagulants and to guide therapy. Drugs such as warfarin can affect the level of or the metabolism of vitamin K in the body, which can impact PT and INR levels. A supratherapeutic INR is rare in a patient not on therapy with vitamin K inhibitors and with preserved liver function. Here we describe an elderly man with a supratherapeutic INR, secondary to the use of rifampin. Antibiotic-induced coagulopathy is an extremely rare complication. To the authors' knowledge, this is a unique case of rifampin-induced coagulopathy with no other associated complications of disseminated intravascular coagulation. A literature review revealed a small number of cases of rifampicin-induced coagulopathy. A high index of suspicion and knowledge is essential for the diagnosis and management of such cases.

LEARNING POINTS: Given the unpredictability and rarity of rifampicin-induced coagulopathy in clinical practice, clinicians should be aware of the possibility of bleeding or drug-induced thromboembolic events with antibiotics.Early recognition and withdrawal of the offending agent are key to the successful management of this condition.Clinicians should be aware of the possible side effects of administered drugs and their possible interactions.

PMID:35774731 | PMC:PMC9239022 | DOI:10.12890/2022_003380

Cureus. 2022 May 29;14(5):e25447. doi: 10.7759/cureus.25447. eCollection 2022 May.

ABSTRACT

Drug-induced liver injury (DILI) is one of the leading causes of acute liver failure in the United States. Antimicrobials are the most common class of drugs implicated in this pathology. Although azithromycin has been documented as a relatively safe drug, one of its rare and potentially fatal side effects is DILI. Diagnosing DILI is difficult because it is a diagnosis of exclusion. Autoimmune hepatitis (AIH) may present similarly to DILI, and a liver biopsy may be needed to differentiate between the two conditions. We present a case of azithromycin-induced liver injury in an asthma exacerbation patient with features of AIH.

PMID:35774698 | PMC:PMC9239290 | DOI:10.7759/cureus.25447