A Potential Role for Nivolumab in the Treatment of Fibrous Dysplasia-Related Pain.

Fibrous dysplasia (FD) is a chronic and progressive disorder of bone growth because of decreased osteoblast formation and osteoclast overactivity. Its main symptoms include pain, fracture, and irregular bone growth. Bisphosphonates are the mainstay of therapy for FD with a primary goal of pain relief. A 50-year-old woman presented to ophthalmology in March 2011 with intermittent proptosis, vertical diplopia, and orbital pain. A computed tomography scan of the head revealed a skull base lesion, which was confirmed to be fibrous dysplasia on bone biopsy. Because of significant headache, she was treated with IV pamidronate monthly starting November 2011, which led to pain reduction. Repeated attempts to decrease the frequency of pamidronate were unsuccessful because of breakthrough pain. Oral alendronate and risedronate did not control her symptoms. She remained on risedronate however because of its convenience. In August 2021, she was diagnosed with metastatic melanoma and started nivolumab. Her headache completely resolved for the first time in 10 years. Although nivolumab, a programmed death-1 blocker, has been used in the treatment of bone malignancy, it has not been previously studied in FD. By suppressing RANK ligand-related osteoclastogenesis, nivolumab decreases cancer-associated bone pain. Our case suggests a potential role for nivolumab in treating FD-associated pain.

A Rare Prolactin-secreting Pituitary Carcinoma With Epidural and Thecal Metastases.

Pituitary carcinomas are rare but associated with significant morbidity and mortality. They remain challenging to diagnose and manage. In this case, we describe a 56-year-old man who presented with erectile dysfunction and binocular vertical diplopia. He had central hypogonadism, secondary adrenal insufficiency, and central hypothyroidism on biochemical testing. His serum prolactin was 1517 mcg/L (1517 ng/mL; reference range 4-15 mcg/L), and his sellar magnetic resonance imaging showed a 2.0 × 2.2 × 3.1 cm pituitary tumor. Pathology revealed a prolactin-secreting carcinoma. Despite treatment with a high-dose dopaminergic, 2 transsphenoidal resections, and 1 course of radiation, prolactin levels continued to rise. He developed metastases to the epidural space and thecal sac from the thoracic to sacral spine, for which he received 12 cycles of temozolomide chemotherapy with initial clinical and biochemical response. This was followed by disease escape and progression. We discuss the clinical and imaging features that warrant a high index of suspicion for pituitary carcinoma and review contemporary treatment.

Adverse events with quetiapine and clarithromycin coprescription: A population-based retrospective cohort study.

Background and Aims: Quetiapine is an atypical antipsychotic predominantly metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme. We studied the risk of adverse events following coprescription of clarithromycin (a strong CYP3A4 inhibitor) versus azithromycin (not a CYP3A4 inhibitor) in quetiapine users. Materials and Methods: This was a population-based retrospective cohort study from 2004 to 2020 in Ontario, Canada in adult quetiapine users newly co-prescribed clarithromycin (n = 16,909) or azithromycin (n = 25,267). The primary outcome was the composite of hospital encounters with encephalopathy (defined as a diagnosis of delirium, disorientation, transient alteration of awareness, transient ischemic attack, or unspecified dementia), a fall, or a fracture within 30 days of new coprescription. Secondary outcomes were individual components of the composite outcome, hospital encounter with computed tomography (CT) head scan, and all-cause mortality. Results: Coprescription of clarithromycin versus azithromycin with quetiapine was associated with a higher risk of the primary composite outcome (365 of 16,909 clarithromycin users [2.2%] vs. 309 of 16,929 azithromycin users [1.8%]; absolute risk increase, 0.34% [95% confidence interval, CI, 0.04-0.63]; relative risk [RR], 1.19 [95% CI, 1.02-1.38]). This was primarily driven by an increase in fragility fractures (78 of 16,909 clarithromycin users [0.5%] vs. 45 of 16,923 azithromycin users [0.3%]; absolute risk increase, 0.20% [95% CI, 0.07-0.32]; RR, 1.74 [95% CI, 1.21-2.52]). Hospital encounters with a CT head scan were higher in clarithromycin users (220 of 16,909 [1.3%] vs. 175 of 16,923 azithromycin users [1.0%]; absolute risk increase, 0.27% [95% CI, 0.04-0.50]; RR, 1.26 [95% CI, 1.04-1.54]), but there was no difference in hospital encounters with encephalopathy, falls, or all-cause mortality between macrolide groups. Conclusion: Among adults taking quetiapine, concurrent use of clarithromycin compared with azithromycin was associated with a small but statistically greater 30-day risk of a hospital encounter for encephalopathy, falls, or fracture, which was predominantly related to a higher rate of fragility fractures.

Childhood food insecurity and incident asthma: A population-based cohort study of children in Ontario, Canada.

BACKGROUND: Childhood food insecurity has been associated with prevalent asthma in cross-sectional studies. Little is known about the relationship between food insecurity and incident asthma. METHODS: We used administrative databases linked with the Canadian Community Health Survey, to conduct a retrospective cohort study of children <18 years in Ontario, Canada. Children without a previous diagnosis of asthma who had a household response to the Household Food Security Survey Module (HFSSM) were followed until March 31, 2018 for new asthma diagnoses using a validated administrative coding algorithm. We used multivariable Cox proportional hazard models to examine the association between food insecurity and incident asthma, and adjusted models sequentially for clinical and clinical/socioeconomic risk factors. As additional analyses, we examined associations by HFSSM respondent type, severity of food insecurity, and age of asthma diagnosis. Moreover, we assessed for interaction between food security and child's sex, household smoking status, and maternal asthma on the risk of incident asthma. RESULTS: Among the 27,746 included children, 5.1% lived in food insecure households. Over a median of 8.34 years, the incidence of asthma was 7.33/1000 person-years (PY) among food insecure children and 5.91/1000 PY among food secure children (unadjusted hazard ratio [HR] 1.24, 95% CI 1.00 to 1.54, p = 0.051). In adjusted analyses associations were similar (HR 1.16, 95% CI 0.91 to 1.47, p = 0.24 adjusted for clinical risk factors, HR 1.24, 95% CI 0.97 to 1.60, p = 0.09 adjusted for clinical/socioeconomic factors). Associations did not qualitatively change by HFSSM respondent type, severity of food insecurity, and age of asthma diagnosis. There was no evidence of interaction in our models. CONCLUSIONS: Food insecure children have numerous medical and social challenges. However, in this large population-based study, we did not observe that childhood food insecurity was associated with an increased risk of incident asthma when adjusted for important clinical and socioeconomic confounders.

Diabetes Management in Older Adults With Chronic Kidney Disease.

PURPOSE OF REVIEW: Older adults often live with chronic disease including diabetes and its complications. In this review, we examine the complexity and heterogeneity of older adults with diabetes and chronic kidney disease, explore the nuances in their diabetes-related monitoring, and discuss their best diabetes management. RECENT FINDINGS: Although there remains an overall lack of studies in older adults with diabetes and chronic kidney disease, recent reports have highlighted their vulnerabilities. These individuals face an increased risk of cognitive impairment and dementia, frailty, dysglycemia, polypharmacy, declining kidney function, and acute kidney injury. Their diabetes management should focus upon safer antihyperglycemic medications, close monitoring, and care individualization. Older adults with diabetes and chronic kidney disease are a complex population who requires careful diabetes management and monitoring. Research efforts might focus on improving the care and outcomes of these patients.

Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study.

OBJECTIVE: To determine whether the use of incretin based drugs compared with sulfonylureas is associated with an increased risk of incident pancreatic cancer in people with type 2 diabetes. DESIGN: Population based cohort. SETTING: Large, international, multicentre study combining the health records from six participating sites in Canada, the United States, and the United Kingdom. PARTICIPANTS: A cohort of 972,384 patients initiating antidiabetic drugs between 1 January 2007 and 30 June 2013, with follow-up until 30 June 2014. MAIN OUTCOME MEASURES: Within each cohort we conducted nested case-control analyses, where incident cases of pancreatic cancer were matched with up to 20 controls on sex, age, cohort entry date, duration of treated diabetes, and duration of follow-up. Hazard ratios and 95% confidence intervals for incident pancreatic cancer were estimated, comparing use of incretin based drugs with use of sulfonylureas, with drug use lagged by one year for latency purposes. Secondary analyses assessed whether the risk varied by class (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) or by duration of use (cumulative duration of use and time since treatment initiation). Site specific hazard ratios were pooled using random effects models. RESULTS: During 2,024,441 person years of follow-up (median follow-up ranging from 1.3 to 2.8 years; maximum 8 years), 1221 patients were newly diagnosed as having pancreatic cancer (incidence rate 0.60 per 1000 person years). Compared with sulfonylureas, incretin based drugs were not associated with an increased risk of pancreatic cancer (pooled adjusted hazard ratio 1.02, 95% confidence interval 0.84 to 1.23). Similarly, the risk did not vary by class and evidence of a duration-response relation was lacking. CONCLUSIONS: In this large, population based study the use of incretin based drugs was not associated with an increased risk of pancreatic cancer compared with sulfonylureas. Although this potential adverse drug reaction will need to be monitored long term owing to the latency of the cancer, these findings provide some reassurance on the safety of incretin based drugs.

Trends in Antihyperglycemic Medication Prescriptions and Hypoglycemia in Older Adults: 2002-2013.

BACKGROUND: Over the last decade, several new antihyperglycemic medications have been introduced including those associated with a lower hypoglycemia risk. We aimed to investigate how these medications are being prescribed to older adults in our region. METHODS: We conducted population-based cross-sectional analyses of older adults (mean age 75 years) with treated diabetes in Ontario, Canada from 2002 until 2013, to examine the percentage prescribed insulin, sulphonylureas, alpha-glucosidase inhibitors, metformin, thiazolidinediones, meglitinides, and dipeptidyl peptidase-4 inhibitors. Over the study period, we also examined their hospital encounters for hypoglycemia (emergency room or inpatient encounter). RESULTS: The mean age of treated patients increased slightly over the study quarters and the proportion that were women declined. With the exception of chronic kidney disease, cancer, dementia, and neuropathy, the percentage with a comorbidity appeared to decline. The percentage of treated patients prescribed metformin, gliclazide and dipeptidyl peptidase-4 inhibitors increased as did combination therapy. Glyburide and thiazolidinedione prescriptions declined, and insulin use remained stable. In those with newly treated diabetes, the majority were prescribed metformin, with smaller percentages prescribed insulin and other oral agents. Although the absolute number of treated patients with a hypoglycemia encounter increased until mid-2006 and then decreased, the overall percentage with an encounter declined over the study period (0.8% with an event in the first quarter, 0.4% with an event in the last quarter). CONCLUSIONS: Antihyperglycemic medications with safer profiles are being increasingly prescribed to older adults. In this setting there has been a decrease in the percentage of treated patients with a hospital encounter for hypoglycemia.