Improving Provider Experience and Increasing Patient Access Through Nurse Practitioner-Physician Primary Care Teams.

Team-based care may address burnout in primary care; few studies have examined the impact of nurse practitioner-physician (NP-MD) teams on provider burnout. This article describes a model of NP-MD care teams in an urban safety-net primary care practice. Average time to third next available appointment with a team provider (either NP or MD) decreased by nearly 20 days after implementation of the model. In total, 79% of MDs reported that the model was very or extremely helpful in reducing the burden of work between visits and 100% of NPs reported that they were very or extremely satisfied with their current job.

BMI and Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer: A Study and Meta-Analysis.

INTRODUCTION: There is only limited data from clinical practice on the relevance of body mass index (BMI) on pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) in patients with breast cancer (BC). PATIENTS AND METHODS: The impact of BMI on pCR and survival outcome was examined in 324 patients with primary non-metastatic BC. An additional meta-analysis was performed on the current data and relevant previously published studies in clinical practice. RESULTS: Multivariable regression analysis identified lymph vascular invasion (odds ratio [OR], 0.05; 95% confidence interval [CI], 0.01-0.18; P = .0000), grading 3 (OR, 3.12; 95% CI, 1.59-6.12; P = .0009), and HER2/neu status (OR, 4.76; 95% CI, 1.86-12.18; P = .011) as independent factors for pCR after NAC. There was no association between pCR and continuous or categorical BMI. Various additional subgroup analyses of molecular BC subtypes (triple-negative, luminal-like, HER2-luminal, HER2-like) and BMI also showed no association. These findings were confirmed by the meta-analysis. Except for one subgroup analysis in which overweight and obese patients were combined as one group, no association between BMI and pCR as well as survival outcome was found. CONCLUSIONS: BMI was not established as a relevant clinical factor. Only lymph vascular invasion, grading 3, luminal-like, and HER2/like BC subtype showed predictive and prognostic impact in patients with BC receiving NAC.

Cholinergic drugs inhibit in vitro megakaryopoiesis via the alpha7-nicotinic acetylcholine receptor.

Besides thrombopoietin several additional factors (i.e neurotransmitters and receptors) are known to be involved in the regulation of megakaryopoiesis at different stages. Recently, we identified functional α7 nicotinic acetylcholine receptors (nAChRα7) on platelets and megakaryocytic precursors. In platelets nAChRα7 form functional Ca(2+) channels and are involved in fibrinogen receptor activation and aggregation. Here, we investigated the impact of nAChRα7 on the differentiation of the human megakaryoblastic cell line MEG-01. In vitro differentiation of MEG-01 cells was induced by the phorbol ester TPA for 5 days in the absence or presence of nicotine or the nAChRα7-selective antagonist methyllycaconitine (MLA), and this was monitored by the expression of the megakaryocytic antigens CD41 and CD61. In the presence of the cholinergic drugs (nicotine or MLA) CD41 and CD61 expression was significantly reduced, both at RNA and protein level. We postulate that the nAChRα7 receptor is involved in megakaryopoietic signal transduction and gene regulation. This could affect the generation of platelets in vivo and contribute to the development of novel therapeutic drugs that regulate platelet formation.

Human platelets express functional alpha7-nicotinic acetylcholine receptors.

OBJECTIVE: Nicotinic acetylcholine receptors, especially α7 (nAChRα7), form Ca(2+) channels and are expressed on a variety of neuronal and nonneuronal cells. Also, megakaryocytic cells have been shown to contain components of a nonneuronal cholinergic system, including acetylcholine and acetylcholine esterase. However, the corresponding nAChRs and their role in platelet function have not been demonstrated until now. Our previous platelet transcriptome data indicated the presence of nAChR gene transcripts. METHODS AND RESULTS: Here, we present evidence that human platelets and megakaryocytic precursor cells express nAChRα7 subunits, as revealed by mRNA and protein expression. The subunits form functional Ca(2+) channels, as demonstrated by Ca(2+) entry in platelets induced by the nAChRα7-selective agonist PNU-282987. PNU-282987 also enhanced fibrinogen receptor activation induced by classical platelet agonists (the thromboxane A(2) analog U46619 and ADP). Furthermore, agonist-induced platelet aggregation was significantly inhibited by the nAChRα7-selective antagonists α-bungarotoxin and methyllycaconitine. CONCLUSIONS: Ca(2+) influx via nAChRα7 channels represents a novel pathway for human platelets with significant impact on platelet function. Because platelets were suggested to contain acetylcholine, we conclude that on activation, stored acetylcholine is released, which activates nAChRα7 channels and thereby contributes to maintaining intracellular Ca(2+) levels and supporting platelet activation.

The Effect of Psychoactive Drugs on in vitro Platelet Function.

BACKGROUND: Neuro-hormonal and hemostatic mechanisms are important in a wide range of psychological and cardiovascular diseases. The use of psychoactive drugs in mental illnesses is often involved with hematologic side effects including impaired platelet function. Subsequently, the risk for the development of cardiovascular diseases may be higher in these patients. Interestingly, platelets that play a key role in cardiovascular complications contain quite a number of neuronal receptors which are involved in psychotic disorders. It has been widely discussed whether psychoactive drugs used in the therapy of psychotic disorders have a direct effect on platelet function and whether the effects are transmitted through the corresponding receptors on the platelet surface. MATERIAL AND METHODS: In this study, we tested several psychoactive drugs regarding their impact on whole blood platelet aggregation. RESULTS: Antidopaminergics preferentially inhibited ADP-induced aggregation whereas anticholinergics mainly inhibited U46619-induced aggregation. Because platelets respond selectively to different psychoactive drugs we assume that corresponding receptors have a functional aspect on platelets and that receptor blockade affects platelet aggregation through different mechanisms. CONCLUSION: The knowledge about the effects of psychoactive drugs on platelet function may help to characterize neuronal receptors on platelets and may contribute to a better understanding of altered platelet function during therapy with psychoactive drugs.