A Review of Concordance and Quality in Clinical Guidelines for Hormonal Contraceptives to Mitigate Drug-Drug Interactions in Women With Epilepsy.

PURPOSE: Concomitant use of hormonal contraceptive agents (HCAs) and enzyme-inducting antiepileptic drugs (EIAEDs) may lead to contraceptive failure and unintended pregnancy. This review identified and evaluated concordance and quality of clinical treatment guidelines related to the use of HCAs in women with epilepsy (WWE) receiving EIAEDs. METHODS: Relevant clinical guidelines were identified across four databases and were independently evaluated for quality utilizing the AGREE-II protocol instrument. Quality in this context is defined as the rigor and transparency of the methodologies used to develop the guideline. Guidelines were further assessed in terms of concordance and discordance with the latest body of knowledge concerning the use of hormonal contraception in the presence of EIAEDs. RESULTS: A total of n = 5 guidelines were retrieved and evaluated. Overall guideline scores ranged from 17% to 92%, while individual domain scores ranged from 0% to 100%. Contraceptive guidelines consistently recommended the use of intrauterine systems and long-acting injectables in the presence of EIAEDs, recommended against the use of oral, transdermal, and vaginal ring contraceptives, and differed regarding recommendations related to implants. Guidelines agreed regarding recommendations that women treated with EIAEDs should receive intrauterine systems and long-acting injectables; however, the suggested frequency of administration of injectable contraceptives differed. The use of intrauterine systems in this population is supported by evidence, but there is uncertainty surrounding the use of long-acting injectables and contraceptive implants. CONCLUSIONS: To mitigate the risk of unintended pregnancy and its consequences, recommendations related to implants and long-acting injectable contraceptives should be evidence-based.

Associations Between Postdischarge Care and Cognitive Impairment-Related Hospital Readmissions for Ketoacidosis and Severe Hypoglycemia in Adults With Diabetes.

OBJECTIVE: Patients with severe hypoglycemia (SH) or diabetic ketoacidosis (DKA) experience high hospital readmission after being discharged. Cognitive impairment (CI) may further increase the risk, especially in those experiencing an interruption of medical care after discharge. This study examined the effect modification role of postdischarge care (PDC) on CI-associated readmission risk among U.S. adults with diabetes initially admitted for DKA or SH. RESEARCH DESIGN AND METHODS: We used the Nationwide Readmissions Database (NRD) (2016-2018) to identify individuals hospitalized with a diagnosis of DKA or SH. Multivariate Cox regression was used to compare the all-cause readmission risk at 30 days between those with and without CI identified during the initial hospitalization. We assessed the CI-associated readmission risk in the patients with and without PDC, an effect modifier with the CI status. RESULTS: We identified 23,775 SH patients (53.3% women, mean age 65.9 ± 15.3 years) and 140,490 DKA patients (45.8% women, mean age 40.3 ± 15.4 years), and 2,675 (11.2%) and 1,261 (0.9%), respectively, had a CI diagnosis during their index hospitalization. For SH and DKA patients discharged without PDC, CI was associated with a higher readmission risk of 23% (adjusted hazard ratio [aHR] 1.23, 95% confidence interval 1.08-1.40) and 35% (aHR 1.35, 95% confidence interval 1.08-1.70), respectively. However, when patients were discharged with PDC, we found PDC was an effect modifier to mitigate CI-associated readmission risk for both SH and DKA patients (P < 0.05 for all). CONCLUSIONS: Our results suggest that PDC can potentially mitigate the excessive readmission risk associated with CI, emphasizing the importance of postdischarge continuity of care for medically complex patients with comorbid diabetes and CI.

High-throughput screening for prescribing cascades among real world statin initiators.

PURPOSE: Statins are among the most prevalent medications prescribed and associated with adverse events that may prompt additional treatment (i.e., a prescribing cascade). No comprehensive assessment of statin-related prescribing cascades has been performed to our knowledge. METHODS: We utilized sequence symmetry analysis to iteratively screen prescribing sequences of all therapeutic classes ("marker" classes) based on Level 4 Anatomical Therapeutic Chemical codes among adult statin initiators, using IBM Marketscan commercial and Medicare supplemental claims databases (2005-2019). Order of initiation and secular trend-adjusted sequence ratios were calculated for each statin-marker class dyad, among marker class initiators ±90 days of statin initiation. Among signals classified as prescribing cascades, we calculated naturalistic number needed to harm (NNTH) within 1 year as the inverse of the excess risk among exposed. RESULTS: We identified 2 265 519 statin initiators (mean ± SD age, 56.4 ± 12.0 years; 48.7% women; 7.5% with cardiovascular disease). Simvastatin (34.4% of statin initiators) and atorvastatin (33.9%) were the most commonly initiated statins. We identified 160 significant statin-marker class dyad signals, of which 35.6% (n = 57) were classified as potential prescribing cascades. Of the top 25 strongest signals (lowest NNTH), 12 were classified as potential prescribing cascades, including osmotically acting laxatives (NNTH, 44, 95% CI 43-46), opioids + non-opioid combination analgesics (81, 95% CI 74-91), and first-generation cephalosporins (204, 95% CI 175-246). CONCLUSIONS: Using high-throughput sequence symmetry analysis screening, we identified previously known prescribing cascades as well as potentially new prescribing cascades based on known and unknown statin-related adverse events.