Modeling the potential benefit of an over-the-counter progestin-only pill in preventing unintended pregnancies in the U.S.

OBJECTIVES: To develop a model to estimate the possible impact of use of an over-the-counter (OTC) progestin-only pill (POP) on the number of unintended pregnancies in the United States. STUDY DESIGN: Using typical use failure rates (7% for POPs), we compared the expected number of unintended pregnancies for two theoretical cohorts of 100,000 women: one which purchased and used an OTC POP exclusively for contraception, the other using contraceptive methods at proportions obtained from an actual-use clinical trial simulating OTC use of norgestrel 0.075 mg (including 35% using no method and only 19% using hormonal contraception or long-acting contraceptives). Sensitivity analyses were conducted using alternative model inputs such as different failure rates for OTC POPs and varied alternative contraceptive method mix. RESULTS: An estimated 37,624 unintended pregnancies would occur annually if 100,000 women continued their usual contraceptive method as used at baseline in the actual use trial. This would be reduced by 81% to 7,000 pregnancies with the exclusive use of an OTC POP - a net reduction of 30,624 unintended pregnancies annually. While the number of unintended pregnancies prevented varied as the model parameters were modified (ranging from 1,461 to 34,124), a net benefit of OTC POP use was observed over a wide range of input values. CONCLUSIONS: Using data from a real-world contraception user profile, our model suggests that use of an OTC POP could reduce the overall number of unintended pregnancies in the United States. This conclusion remains true across a wide range of modeled scenarios. IMPLICATIONS: The estimates suggested by this model are supportive of an OTC switch for a POP.

Cerebrotendinous xanthomatosis-associated diarrhea and response to chenodeoxycholic acid treatment.

BACKGROUND: In patients with cerebrotendinous xanthomatosis (CTX), chronic diarrhea is one of the earliest and main symptoms of the disease. In the current study, we evaluated the characteristics of the diarrhea and its response to chenodeoxycholic acid (CDCA) therapy in a cohort of Dutch CTX patients. METHODS: We performed a retrospective review of medical records for 33 genetically confirmed CTX patients, and abstracted the characteristics of the diarrhea and the response to CDCA therapy (15 mg/kg/day up to 750 mg/day). The Bristol Stool Scale (BSS) was used for qualitative characterization of the stool. RESULTS: Twenty-five patients had diarrhea documented at baseline (76%). Of these patients, 10 had diarrhea rated as 6 (fluffy pieces with ragged edges, a mushy stool), and 6 had diarrhea rated as 7 (watery, no solid pieces, entirely liquid) using the BSS. In 10 patients for whom data were recorded, the median stool frequency at baseline was 3 per day (range 2-6 per day). The response rate with CDCA for diarrhea resolution was 100% based on at least one post-baseline visit without diarrhea and 95% as assessed at the first post-baseline visit. In 68% of cases resolution was complete and sustained as no episodes of diarrhea were documented for follow-up periods as long as 25 years. CONCLUSIONS: Chronic diarrhea persisting for years without spontaneous remission is a common feature of CTX at diagnosis. Chenodeoxycholic acid is an effective treatment for symptomatic relief of diarrhea in patients with CTX.

Poison center exposures due to therapeutic misuse of nonprescription acetaminophen-containing combination products in the United States 2007-2016.

BACKGROUND: Overdoses due to therapeutic misuse result when the maximum dose of a drug is exceeded while using it for its intended purpose, due to either intentionally exceeding the label dose, misunderstanding the label or use of more than one product with the same ingredient. Nonprescription acetaminophen-containing combination products have been hypothesized to be a risk for therapeutic misuse. This study assessed the contribution of nonprescription acetaminophen-containing products to Poison Center exposures and the time trend in these exposures since public attention was brought to their potential risks. METHODS: The National Poison Data System (NPDS) was used to identify exposures involving acetaminophen-containing products in individuals 12 years or older for the period 2007-2016. Exposures due to therapeutic misuse of nonprescription acetaminophen-containing combination products were identified and demographic and clinical features of these exposures tabulated. Product sale and US population data were used to normalize the exposures. RESULTS: Therapeutic misuse exposures involving nonprescription acetaminophen-containing combination products decreased from 8753 in 2007 to 6278 in 2016. The majority of exposures occurred in individuals 12-29 years of age. The rate of therapeutic misuse exposures was highest in the 12-19 years of age cohort with an estimated 638 exposures per million population per 10 years. More than one acetaminophen-containing product was involved in 24.8% of exposures. Individuals were hospitalized in 5.4% of exposures and 51 deaths occurred in the 10-year observation period in reported exposures. CONCLUSIONS: NPDS exposures due to therapeutic misuse of nonprescription acetaminophen-containing combination products are infrequent and the number of exposures decreased from 2007 to 2016. Nonetheless, these exposures impact poison centers, healthcare facilities and patients. Additional initiatives to educate consumers on the safe use of these products and innovative labeling efforts to prevent concurrent use of multiple acetaminophen-containing products should be continued and are encouraged.

The Effectiveness of Nonprescription Drug Labels in the United States: Insights from Recent Research and Opportunities for the Future.

Despite providing a consistent and comprehensible format for over-the-counter (OTC) drug communication, research suggests important limitations in the communication effectiveness of the Drug Facts Label required on OTC drugs in the United States. This literature is reviewed and some of these critical limitations of the Drug Facts Label (DFL) highlighted. These include difficulty communicating complex information that requires integration of multiple pieces of label information and limited adaptability to serve the unique needs of individual populations (e.g., low literacy or older consumers). Potential ways to improve the DFL's communication effectiveness are identified along with complementary opportunities to improve OTC drug communication by leveraging the role of pharmacists and use of adjunctive technologies.

Frequency of Poison Center Exposures for Pediatric Accidental Unsupervised Ingestions of Acetaminophen after the Introduction of Flow Restrictors.

OBJECTIVE: To assess the temporal association of flow restrictor introduction and the rate of accidental unsupervised ingestions (AUIs) of liquid acetaminophen products. STUDY DESIGN: The National Poison Data System was used to identify AUIs of single ingredient acetaminophen in patients aged <12 years reported between 2007 and 2015. Six regional poison centers obtained additional information using a structured telephone survey. RESULTS: Pediatric AUIs involving acetaminophen averaged 30 000 exposures per year between 2007 and 2012. From 2012 to 2015, after flow restrictor introduction, exposures steadily decreased at a rate of 2400 fewer exposures annually, reaching 21 877 exposures in 2015. Normalized to sales volume, exposures involving liquid acetaminophen products decreased by 40% from 2010 to 2015. Exposures involving products with flow restrictors tended to have a lower estimated ingestion per exposure, fewer exposures exceeding a 150 mg/kg acetaminophen threshold, and were associated with lower rates of hospital admissions when compared with products without restrictors. Caregivers reported improper storage and child confusion of the medicine with treats as common contributing factors to exposures. CONCLUSIONS: The introduction of flow restrictors was associated with a decrease in pediatric AUIs of liquid acetaminophen products. Decreases in the dose ingested and risk of hospital admission per exposure may also have resulted. Efforts to optimize flow restrictors and increase their use with medicines associated with high pediatric overdose risk should be encouraged.

Medication Errors With Pediatric Liquid Acetaminophen After Standardization of Concentration and Packaging Improvements.

OBJECTIVE: To assess the impact of the 2011 changes in pediatric single-ingredient liquid acetaminophen product packaging and standardization of the acetaminophen concentration (160 mg/5 mL) on poison control center exposures due to medication errors. METHODS: National Poison Data System (NPDS) data from January 1, 2007, through December 31, 2016, were used to identify medication error exposures involving single-ingredient liquid acetaminophen in children younger than 12 years of age. Surveys were conducted through 6 regional poison control centers to obtain additional information on a subset of exposures. RESULTS: The annual frequency of NPDS exposures due to medication errors with single-ingredient liquid acetaminophen products was 8260 ± 670 exposures/year during 2007-2011. Children <2 years of age accounted for 66% of exposures. The overall rate of exposures fell to 6669 ± 662 during 2012-2016 (19% decrease; P = .005). Four percent of exposures led to health care facility referrals. Caregivers involved with exposures in children <2 years of age cited health professionals as the source of dosing information in only 69% of cases despite the absence of specific dosing directions for these children on product labels. CONCLUSIONS: Implementation of a single concentration for pediatric liquid acetaminophen products and packaging changes were associated with a decrease in medication errors reported to poison control centers. Medication errors are particularly problematic for children <2 years of age, for whom there are no specific labeled dosing instructions. Improved efforts to provide caregivers with dosing instructions for these children are encouraged.

Pathogenesis of the limb manifestations and exercise limitations in peripheral artery disease.

Patients with peripheral artery disease have a marked reduction in exercise performance and daily ambulatory activity irrespective of their limb symptoms of classic or atypical claudication. This review will evaluate the multiple pathophysiologic mechanisms underlying the exercise impairment in peripheral artery disease based on an evaluation of the current literature and research performed by the authors. Peripheral artery disease results in atherosclerotic obstructions in the major conduit arteries supplying the lower extremities. This arterial disease process impairs the supply of oxygen and metabolic substrates needed to match the metabolic demand generated by active skeletal muscle during walking exercise. However, the hemodynamic impairment associated with the occlusive disease process does not fully account for the reduced exercise impairment, indicating that additional pathophysiologic mechanisms contribute to the limb manifestations. These mechanisms include a cascade of pathophysiological responses during exercise-induced ischemia and reperfusion at rest that are associated with endothelial dysfunction, oxidant stress, inflammation, and muscle metabolic abnormalities that provide opportunities for targeted therapeutic interventions to address the complex pathophysiology of the exercise impairment in peripheral artery disease.

Patient and hospital-level characteristics associated with the use of do-not-resuscitate orders in patients hospitalized for sepsis.

BACKGROUND: Identifying factors associated with do-not-resuscitate (DNR) orders is an informative step in developing strategies to improve their use. As such, a descriptive analysis of the factors associated with the use of DNR orders in the early and late phases of hospitalizations for sepsis was performed. METHODS: A retrospective cohort of adult patients hospitalized for sepsis was identified using a statewide administrative database. DNR orders placed within 24 h of hospitalization (early DNR) and after 24 h of hospitalization (late DNR) were the primary outcome variables. Multivariable logistic regression analysis was used to identify patient, hospital, and healthcare system-related factors associated with the use of early and late DNR orders. RESULTS: Among 77,329 patients hospitalized for sepsis, 27.5 % had a DNR order during their hospitalization. Among the cases with a DNR order, 75.5 % had the order within 24 h of hospitalization. Smaller hospital size and the absence of a teaching program increased the likelihood of an early DNR order being written. Additionally, greater patient age, female gender, White race, more medical comorbidities, Medicare payer status and admission from a skilled nursing facility were all significantly associated with the likelihood of having an early DNR. The strength of association between these factors and the use of late DNR orders was weaker. In contrast, the greater the burden of medical comorbidities, the more likely a patient was to receive a late DNR order. CONCLUSION: Multiple patient, hospital, and healthcare system-related factors are associated with the use of DNR orders in sepsis, many of which appear to be independent of a patient's clinical status. Over the course of the hospitalization, the burden of medical illness shows a stronger association relative to other variables. The influence of these multi-level factors needs to be recognized in strategies to improve the use of DNR orders. .

Resident's morning report: an opportunity to reinforce principles of biomedical science in a clinical context.

The principles of biochemistry are core to understanding cellular and tissue function, as well as the pathophysiology of disease. However, the clinical utility of biochemical principles is often obscure to clinical trainees. Resident's Morning Report is a common teaching conference in which residents present clinical cases of interest to a faculty member for discussion. This venue provides an opportunity to illustrate how basic biomedical principles facilitate an understanding of the clinical presentation, the relevant pathophysiology, and the rationale for diagnostic and therapeutic strategies. A discussion of biochemical principles can easily be incorporated into these case discussions, with the potential to reinforce these concepts and to illustrate their application to clinical decision making. This approach maintains the effort to teach basic biomedical sciences in the context of clinical application across the educational continuum.