A Pilot Randomized Trial of Transdermal Nicotine for Pulmonary Sarcoidosis.

BACKGROUND: Tobacco smoking is associated with a reduced risk of developing sarcoidosis, and we previously reported that nicotine normalizes immune responses to environmental antigens in patients with active pulmonary sarcoidosis. The effects of nicotine on the progression of pulmonary sarcoidosis are unknown. RESEARCH QUESTION: Is nicotine treatment well tolerated, and will it improve lung function in patients with active pulmonary sarcoidosis? STUDY DESIGN AND METHODS: With local institutional review board approval, a randomized, double-blind, controlled pilot trial was conducted of daily nicotine transdermal patch treatment (21 mg daily) or placebo patch use for 24 weeks. The Ohio State University Wexner Medical Center and Cleveland Clinic enrolled 50 consecutive subjects aged ≥ 18 years with active pulmonary sarcoidosis, based on symptoms (ie, dyspnea, cough) and objective radiographic evidence of infiltrates consistent with nonfibrotic lung disease. Each study group was compared at 26 weeks based on repeated measures of FVC, FEV1, quantitative lung texture score based on CT texture analysis, Fatigue Assessment Score (FAS), St. George's Respiratory Questionnaire (SGRQ), and the Sarcoidosis Assessment Tool. RESULTS: Nicotine treatment was associated with a clinically significant, approximately 2.1% (70 mL) improvement in FVC from baseline to 26 weeks. FVC decreased by a similar amount (2.2%) in the placebo group, with a net increase of 140 mL (95% CI, 10-260) when comparing nicotine vs placebo groups at 26 weeks. FEV1 and FAS improved marginally in the nicotine-treated group, compared with those on placebo. No improvement was observed in lung texture score, FAS, St. George's Respiratory Questionnaire score, or the Sarcoidosis Assessment Tool. There were no reported serious adverse events or evidence of nicotine addiction. INTERPRETATION: Nicotine treatment was well tolerated in patients with active pulmonary sarcoidosis, and the preliminary findings of this pilot study suggest that it may reduce disease progression, based on FVC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02265874; URL: www.clinicaltrials.gov.

Family-centered communication: A pilot educational intervention using deliberate practice and patient feedback.

OBJECTIVE: There are few opportunities in medical education dedicated to learning skills for effective communication in life altering patient scenarios. We therefore aimed to develop and assess a longitudinal advanced communication curriculum for pediatric residents using patient feedback and deliberate practice. METHODS: Pediatric residents at a large academic center were randomized into 2 groups. The intervention group received 6 educational sessions from 2019 to 2020, parent feedback of performance via the Communication Assessment Tool (CAT), and monthly communication tips. Communication skills of both groups were assessed at the end of the intervention. RESULTS: We collected 937 CAT assessments on 36 first-year residents. The intervention group demonstrated statistically significant improvement in communication skills from pre to post assessment (p = 0.0063, (odds ratio (OR) 1.76, 95 % confidence interval (CI) [1.17, 2.63]) compared to the control group (p = 0.080, OR 1.41, 95 % CI [0.96, 2.05]). CONCLUSIONS: There are patient and self-identified performance gaps in communication skills for pediatric residents, underscoring the need for formalized curricula dedicated to these skills. PRACTICE IMPLICATIONS: Our study highlights the value of deliberate practice and the integration of family feedback as an educational tool in communication skills development.

Evolution of correlated complexity in the radically different courtship signals of birds-of-paradise.

Ornaments used in courtship often vary wildly among species, reflecting the evolutionary interplay between mate preference functions and the constraints imposed by natural selection. Consequently, understanding the evolutionary dynamics responsible for ornament diversification has been a longstanding challenge in evolutionary biology. However, comparing radically different ornaments across species, as well as different classes of ornaments within species, is a profound challenge to understanding diversification of sexual signals. Using novel methods and a unique natural history dataset, we explore evolutionary patterns of ornament evolution in a group-the birds-of-paradise-exhibiting dramatic phenotypic diversification widely assumed to be driven by sexual selection. Rather than the tradeoff between ornament types originally envisioned by Darwin and Wallace, we found positive correlations among cross-modal (visual/acoustic) signals indicating functional integration of ornamental traits into a composite unit-the "courtship phenotype." Furthermore, given the broad theoretical and empirical support for the idea that systemic robustness-functional overlap and interdependency-promotes evolutionary innovation, we posit that birds-of-paradise have radiated extensively through ornamental phenotype space as a consequence of the robustness in the courtship phenotype that we document at a phylogenetic scale. We suggest that the degree of robustness in courtship phenotypes among taxa can provide new insights into the relative influence of sexual and natural selection on phenotypic radiations.

Potential drug interaction with opioid agonist in the setting of chronic low-dose opioid antagonist use.

Low dose naltrexone (LDN) has been evaluated in several small studies for the treatment of inflammatory conditions. It is thought to work through modulation of inflammatory mediators and upregulation of endogenous opioid receptors. This may hypersensitize patients to exogenous opioids. Drug-drug interaction screening tools built into electronic health records and other services identify the interaction as risk of opioid withdrawal rather than hypersensitivity. We present a case of a drug-drug interaction in a patient who was receiving LDN treatment of multiple sclerosis. The patient received a single dose of oxycodone 5mg that resulted in obtundation unresponsive to painful stimuli necessitating the administration of naloxone boluses and infusion along with admission to the intensive care unit for 1 night. The patient responded well to naloxone therapy. He was discharged in satisfactory condition.