Implementation of Recommendations for Long-Acting Contraception Among Women Aged 13 to 18 Years in Primary Care

ObjectiveClinical specialty societies recommend long-acting reversible contraceptives (LARCs) as first-line contraception for adolescent women. We evaluated whether a combined educational and process improvement intervention enhanced LARC placement in primary care within an integrated health care system.MethodsThe intervention included journal clubs, live continuing education, point-of-care guidelines, and new patient materials. We conducted a retrospective cohort study across 3 time periods: baseline (January 2013?September 2015), early implementation (October 2015–March 2016), and full implementation (April 2016–June 2017). The primary outcome was the proportion of LARCs placed by primary care clinicians among women aged 13 to 18 years compared with gynecology clinicians.ResultsKaiser Foundation Health Plan of Colorado cared for approximately 20,000 women aged 13 to 18 years in each calendar quarter between 2013 and 2017. Overall, LARC placement increased from 7.0 per 1000 members per quarter at baseline to 13.0 per 1000 during the full intervention. Primary care clinicians placed 6.2% of all LARCs in 2013, increasing to 32.1% by 2017 (P < .001), including 45.5% of contraceptive implants. Clinicians who attended educational sessions were more likely to adopt LARCs than those who did not (17.9% vs 6.4% respectively, P = .009). Neither overall LARC placement rates (relative risk, 1.9; 95% confidence interval, 0.7?5.6) nor contraceptive implant rates (relative risk, 3.0; 95% confidence interval, 0.9?9.8) increased significantly in clinicians who attended educational activities.ConclusionsThis multimodal intervention was associated with increased LARC placement for adolescent women in primary care. The combination of education and process improvement is a promising strategy to promote clinician behavior change.     

Balloon embolization to occlude a Blalock-Taussig shunt

Balloon embolization was used to successfully occlude a large residual Blalock-Taussig shunt. The use of an "upstream" nondetachable balloon catheter to reduce flow and turbulence during final positioning of the detachable balloon may have made the technique safer and more precise.     

The involvement of clathrin‐mediated endocytosis and two Sid‐1‐like transmembrane proteins in double‐stranded RNA uptake in the Colorado potato beetle midgut

RNA interference (RNAi) is a powerful tool in entomology and shows promise as a crop protection strategy, but variability in its efficiency across different insect species limits its applicability. For oral uptake of the double‐stranded RNA (dsRNA), the RNAi trigger, two different mechanisms are known: systemic RNA interference deficient‐1 (Sid‐1) transmembrane channel‐mediated uptake and clathrin‐mediated endocytosis. So far, a wide range of experiments has been conducted, confirming the involvement of one of the pathways in dsRNA uptake, but never both pathways in the same species. We investigated the role of both pathways in dsRNA uptake in the Colorado potato beetle, Leptinotarsa decemlineata, known to have an efficient RNAi response. Through RNAi‐of‐RNAi experiments, we demonstrated the contribution of two different sid‐1‐like (sil) genes, silA and silC, and clathrin heavy chain and the 16kDa subunit of the vacuolar H⁺ ATPase (vha16), elements of the endocytic pathway, to the RNAi response. Furthermore, the sid‐1‐like genes were examined through phylogenetic and hydrophobicity analysis. This article reports for the first time on the involvement of two pathways in dsRNA uptake in an insect species and stresses the importance of evaluating both pathways through a well‐devised reporter system in any future experiments on cellular dsRNA uptake.     

Renal Effects of Crizotinib in Patients With ALK-Positive Advanced NSCLC

IntroductionWe retrospectively analyzed the effects of crizotinib on serum creatinine and creatinine-based estimated glomerular filtration rate (eGFR) in patients with anaplastic lymphoma kinase–positive advanced NSCLC across four trials (NCT00585195, NCT00932451, NCT00932893, and NCT01154140).MethodsChanges from baseline data in serum creatinine and eGFR, calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine-based equation, were assessed over time. eGFR was graded using standard chronic kidney disease criteria.ResultsMedian serum creatinine increased from 0.79 mg/dL at baseline to 0.93 mg/dL after 2 weeks of treatment (median percentage increase from baseline, 21.2%), was stable from week 12 (0.96 mg/dL) to week 104 (1.00 mg/dL), and decreased to 0.90 mg/dL at 28 days after last dose (median percentage increase from baseline, 13.1%). Median eGFR decreased over time (96.42, 80.23, 78.06 and 75.45 mL/min/1.73 m² at baseline, week 2, week 12, and week 104, respectively) and increased to 83.02 mL/min/1.73 m² at 28 days after the last dose. Median percentage decrease from baseline was 14.9%, 17.0%, and 10.4% at week 2, week 12, and 28 days after last dose of crizotinib, respectively. Overall, 12.6% of patients had a shift from eGFR grade less than or equal to 3a (≥45 mL/min/1.73 m²) at baseline to greater than or equal to 3b (<45 mL/min/1.73 m²) post-baseline.ConclusionsCrizotinib resulted in a decline in creatinine-based estimates of renal function mostly over the first 2 weeks of treatment. However, there was minimal evidence of cumulative effects with prolonged treatment and these changes were largely reversible following treatment discontinuation, consistent with previous reports suggesting this may be predominantly an effect on creatinine secretion as opposed to true nephrotoxicity.     

Plasma antidiuretic hormone in acute respiratory failure

The role of antidiuretic hormone (ADH) in the pathogenesis of renal impaired water excretion in acute respiratory failure has not been clearly delineated. Plasma sodium concentration and plasma ADH levels (radioimmunoassay) were therefore serially measured in 13 patients with acute respiratory failure (10 with acute exacerbations of chronic lung disease and three with acute lung disease) and eight “control” patients admitted to the intensive care unit with suspected myocardial infarction. None of the patients had systemic hemodynamic, hepatic or renal dysfunction. ADH levels were significantly elevated in patients with acute respiratory failure (15.1 ± 5.2 pg/ml versus 5.7 ± 1.9 pg/ml, p < 0.05) when compared with levels in control patients. The elevated ADH levels occurred despite significantly lower plasma sodium concentration (133 ± 1 meq/liter versus 138 ± 2 meq/liter, p < 0.05) compared with control values. Moreover, markedly increased ADH values (range 1.1 to 13.0 pg/ml) were often encountered in patients with acute respiratory failure despite significant hyposmolality (263 to 275 mOsm/kg H₂O). This was not observed in any control patients. These results suggest that patients with acute respiratory failure are susceptible to water retention and hyposmolality due to nonosmotic release of antidiuretic hormone.     

Prediction of maximal cardiac output in preoperative patients with coronary artery disease

Of 100 patients (89 men, 11 women) studied preoperatively to determine their aerobic and hemodynamic profiles at rest and during upright treadmill exercise. The mean maximal cardiac output (CO), measured using the direct Fick principle, was 57 ± 14% of average normal values. The reduction in maximal heart rate (63 ± 13% of normal) was a greater factor in the reduction in CO than stroke volume (88 ± 16% of normal). Maximal oxygen consumption (V?O₂max) was 48 ± 15% of normal and the greater reduction in V?O₂₂max compared with CO was due to lower peripheral extraction in the coronary patients. Variables that correlated with maximal CO in a univariate analysis included angina severity (r = ?0.45), V?O₂₂max (r = 0.67), maximal heart rate (r = ?0.31), left ventricular dysfunction (r = ?0.45), maximal systolic blood pressure (r = ?0.31) and number of vessels with ≥ 50% diameter reduction (r = ?0.3). Resting ejection fraction did not correlate with maximal CO. In a multivariate analysis, 4 variables correlated significantly (r = 0.77) with maximal CO: in order, V?O₂₂max, number of vessels with ≥ 50% stenosis, magnitude of ST depression and sex.