Rituximab and Pyoderma Gangrenosum: An Investigation of Disproportionality Using a Systems Biology-Informed Approach in the FAERS Database.

BACKGROUND: Studies have found an increased risk of pyoderma gangrenosum associated with rituximab. The structural properties and pharmacological action of rituximab may affect the risk of pyoderma gangrenosum. Additionally, pyoderma gangrenosum is associated with autoimmune disorders for which rituximab is indicated. OBJECTIVE: We aimed to determine whether rituximab is disproportionally associated with pyoderma gangrenosum using a systems biology-informed approach. METHODS: Adverse event reports were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS, 2013-20). The Bayesian Confidence Propagation Neural Network Information Component was used to test for disproportionality. Comparators used to determine potential causal pathways included all other medicines, all medicines with a similar structure (monoclonal antibodies), all medicines with the same pharmacological target (CD20 antagonists) and all medicines used for the same indication(s) as rituximab. RESULTS: Thirty-two pyoderma gangrenosum cases were identified, 62.5% were female, with a median age of 48 years. There was an increased association of pyoderma gangrenosum with rituximab compared with all other medicines (exponentiated Information Component 6.75, 95% confidence interval (CI) 4.66-9.23). No association was observed when the comparator was either monoclonal antibodies or CD20 antagonists. Conditions for which an association of pyoderma gangrenosum with rituximab was observed were multiple sclerosis (6.68, 95% CI 1.63-15.15), rheumatoid arthritis (2.67, 95% CI 1.14-4.80) and non-Hodgkin's lymphoma (2.94, 95% CI 1.80-3.73). CONCLUSIONS: Pyoderma gangrenosum was reported more frequently with rituximab compared with all other medicines. The varying results when restricting medicines for the same condition suggest the potential for confounding by indication. Post-market surveillance of biologic medicines in  FAERS should consider a multi-faceted approach, particularly when the outcome of interest is associated with the underlying immune condition being treated by the medicine of interest.

Pharmacist-Initiated Management of a Suspected Case of Risperidone-Induced Neuroleptic Malignant Syndrome in an Aged-Care Resident. The Role of Residential Medication Management Reviews in Medication Safety.

A 70-year-old female aged-care resident was referred by her general practitioner for a residential medication management review after nurses reported difficulties with swallowing, episodes of hyperthermia, elevated blood pressure, and tachycardia. These symptoms were accompanied by increasing confusion and drowsiness. Risperidone had recently been prescribed to treat behavioral and psychological symptoms of dementia. This case study describes the pharmacist-initiated management of the symptoms through a national medication review program. It demonstrates the valuable role collaborative medication reviews play in managing adverse drug reactions in aged-care.

Safety and effectiveness of cannabinoids for the treatment of neuropsychiatric symptoms in dementia: a systematic review.

BACKGROUND: Neuropsychiatric symptoms (NPS) in dementia impact profoundly on the quality of life of people living with dementia and their care givers. Evidence for the effectiveness and safety of current therapeutic options is varied. Cannabinoids have been proposed as an alternative therapy, mainly due to their activity on CB1 receptors in the central nervous system. However, little is known regarding the safety and effectiveness of cannabinoid therapy in people with dementia. A literature review was undertaken to identify, describe and critically appraise studies investigating cannabinoid use in treating NPS in dementia. METHODS: We undertook a systematic review adhering to PRISMA guidelines. Twenty-seven online resources were searched, including Medline, PsycINFO and Embase. Studies assessing the safety and or effectiveness of cannabinoids in treating NPS in dementia in people aged ⩾ 65 years were included. Study quality was assessed using the Johanna Briggs Institute and Cochrane Collaboration critical appraisal tools. RESULTS: Twelve studies met the inclusion criteria. There was considerable variability across the studies with respect to study design (50% randomized controlled trials), intervention [dronabinol (33%), nabilone (25%) or delta-9 tetrahydrocannabinol (THC; 42%)] and outcome measures. Dronabinol (three studies) and THC (one study) were associated with significant improvements in a range of neuropsychiatric scores. The most common adverse drug event (ADE) reported was sedation. A high risk of bias was found in eight studies. The highest-quality trial found no significant improvement in symptoms or difference in ADE rate between treatment arms. Included studies used low doses of oral cannabinoids and this may have contributed to the lack of demonstrated efficacy. CONCLUSION: While the efficacy of cannabinoids was not proven in a robust randomized control trial, observational studies showed promising results, especially for patients whose symptoms were refractory. In addition, the safety profile is favourable as most of the ADEs reported were mild. Future trials may want to consider dose escalation and formulations with improved bioavailability.

Disease burden, comorbidity and geriatric syndromes in the Australian aged care population.

OBJECTIVE: To describe the burden of disease in the Australian residential aged care population. METHODS: Cross-sectional analysis of Aged Care Funding Instrument data. RESULTS: Dementia (48%), depression (22.5%) and arthritis (14.2%) were the most prevalent chronic diseases in this population. Unclassified conditions such as falls, pain and urinary incontinence were also significant burdens in this population (17.1%). Circulatory, musculoskeletal and unclassified conditions were the most prevalent comorbidities across all common medical groups. Dementia and depression were the most common comorbid mental health conditions across all medical groups. CONCLUSION: The challenges for evaluating clinical care in Australian residential aged care are many. Delivering good clinical care should be a priority for aged care providers given the high burden of chronic disease and comorbidity. An informative starting point could be to target management of the most prevalent and burdensome conditions and comorbidities.