Alpelisib, a phosphatidylinositol-3-kinase (PI3K) inhibitor, is a new drug approved for metastatic breast cancer. Hyperglycemia is a known side effect of this medication, however diabetic ketoacidosis is rarely described. We are presenting a 64-year-old female with a known case of Type 2 diabetes mellitus (hemoglobin A1c [HbA1c] 5.6% ) controlled by metformin alone. She was also diagnosed with metastatic breast cancer. She received radiotherapy, trastuzumab and letrozole. Then, she was started on alpelisib as she failed other previous modalities. She presented to the emergency department with a two-week history of polyuria and polydipsia, and laboratory investigation results showed high anion gap metabolic acidosis, ketonemia, and hyperglycemia. She was treated for diabetic ketoacidosis (DKA). After the resolution of DKA, she was kept on daily insulin subcutaneous injections. She was restarted on a reduced dose of alpelisib, but despite this, her blood sugar readings continued to rise, requiring discontinuation of the medication with a resolution of hyperglycemia. The goal of our case report is to emphasize the importance of close glucose monitoring when starting alpelisib to avoid serious complications like DKA.

Polypharmacy in people living with HIV/AIDS (PLWHA) is a rising morbidity that exacts hefty economic burden on health budgets in addition to other adverse clinical outcomes. Despite recent advances, uncertainty remains around its exact definition in PLWHA. In this systematic review and Meta-analysis, we explored relevant databases (PUBMED, EMBASE, CROI) for studies evaluating polypharmacy in PLWHA from January 2000 to August 2021 to ascertain the exact numerical threshold that defines this morbidity. Two independent reviewers extracted and reviewed relevant variables for analyses. The review included a total of 31 studies involving n = 53,347 participants with a mean age of 49.5 (SD ± 17.0) years. There was a total of 36 definitions, with 93.5% defining polypharmacy as the concomitant use of 5 or more medications. We found significant variation in the numerical definition of polypharmacy, with studies reporting it as “minor” (N = 3); “major” (N = 29); “severe” (N = 2); “excessive” (N = 1); and “higher” (N = 1). Most studies did not incorporate a duration (84%) in their definition and excluded ART medications (67.7%). A plurality of studies in PLWHA have established that polypharmacy in this cohort of patients is the intake of ≥ 5 medications (including both ART and non-ART). To standardize the approach to addressing this rising morbidity, we recommend incorporation of this definition into national and international PLWHA treatment guidelines.

Background Despite its central role in drug metabolism, there is still residual uncertainty regarding the rising burden as well as exact definition of polypharmacy in patients with chronic liver disease. Methods We carried out a systematic search of EMBASE, PUBMED, Cochrane Database of Systematic Reviews, Science Citation Index, and Database of Abstracts of Reviews of Effects (DARE) between 1st January 2000 and 30th January 2022 for studies exploring polypharmacy in patients with chronic liver disease. We excluded studies that had no explicit numerical or descriptive definition of polypharmacy. Results We retrieve (N = 171) reports from systematic literature search with six studies (N = 918 548 patients) meeting criteria for inclusion in the review. A total of (N = 8) iterations of polypharmacy definitions were retrieved with numerical definitions (≥ 5 medications) constituting up about 62.5% of this. The latter is the most reported definition of polypharmacy. Two studies described polypharmacy based on the duration of exposure. None of the reviewed studies examined the constituent of polypharmacy (i.e., whether liver-related or non-liver related medications). Conclusion In a systematic review of current reports on medication counts in patients with chronic liver disease, we found an intake of 5 or more medications as consistent with the definition of polypharmacy in this patient cohorts. It remains uncertain if adoption of “non-liver related polypharmacy” as a definition will best characterize this therapeutic morbidity in these cohorts of patients. Prospero Number: CRD42022306572