Increasing statin prescription rates to prevent cardiovascular disease among high-risk populations: a quality improvement intervention centred on a novel interactive tool.

Statins are indicated for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Our previous study of 1042 consecutive patient encounters at our large urban academic institution found that one in five patients were not prescribed an appropriate statin therapy. Only one-third of patients had follow-up cholesterol levels ordered to monitor treatment efficacy. In order to improve adherence to cholesterol guidelines at our institution, a quality improvement project was undertaken. We implemented interventions over a 4-month period to improve statin prescription rates: (a) development of an online interactive tool, (b) physician education on updated cholesterol guidelines and utilisation of the tool, (c) display of guideline summary in the workspace and (d) a documentation reminder in the electronic health record. We randomly selected encounter dates, from which 622 consecutive patient encounters were analysed. The primary outcome measures were prescription rates of statins, documentation of a 10-year ASCVD risk score and follow-up cholesterol levels ordered to monitor treatment efficacy. Out of the 622 patient encounters, 232 met statin indication. In this post-intervention group, statin prescription rates improved when compared with the pre-intervention group (90.5% vs 82.3%, p=0.006). Among patients who met statin indication solely via a 10-year ASCVD risk score ≥7.5%, there was an increase in documentation of the calculated 10-year ASCVD risk score (72.3% vs 57.8%; p=0.039) and in statin prescription rate (90.8% vs 67.6%; p<0.001). In addition, there was an increase in follow-up cholesterol levels ordered in all patients included in our study who met statin indication (64.1% vs 33.3%; p<0.001). Our quality improvement project showed higher rates of statin prescription, 10-year ASCVD risk score documentation and treatment monitoring after multiple interventions, centred on an easily accessible online interactive tool.

Pulmonary Large Cell Neuroendocrine Carcinoma: A Rare Type of Non-Small Cell Lung Cancer.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is an uncommon type of non-small cell lung cancer (NSCLC) with an incidence of approximately 3% of all lung cancer diagnoses. The patient was a 60-year-old male with a 90-pack year smoking history who presented with dyspnea on exertion and productive cough for five weeks. Decreased breath sounds without respiratory distress and generalized cachexia were noted on the initial physical exam. Laboratory results were unremarkable except for chronic microcytic anemia. Computed tomography revealed extensive lymphadenopathy of the paratracheal, paraaortic, hilar, and nodes surrounding the left pulmonary arteries. Additionally, there were areas of necrosis in the left upper lobe, lingula, and left lower lobe with extensive pleural thickening extending to the abdomen and subcutaneous tissue of the anterior chest wall. Biopsy and staining showed disorganized tight cell clusters with irregular and prominent nuclei and numerous lymphocytes consistent with LCNEC. Immunohistochemistry was positive for neural cell adhesion molecule CD56 and synaptophysin, which was indicative of neuroendocrine origin. It was also positive for pan-cytokeratin antibody AE1 and AE3 and cytokeratin (CAM) 5.2, which arise from epithelial origin consistent with NSCLCs. Lastly, the patient's tissue was positive for thyroid transcription factor-1, which confirmed the tumor's primary lung origin. This combination of neuroendocrine and primary lung tumor markers, in conjunction with the histology, confirmed the patient's diagnosis of LCNEC.

Cell origin, volume and arrangement are drivers of articular cartilage formation, morphogenesis and response to injury in mouse limbs.

Limb synovial joints are composed of distinct tissues, but it is unclear which progenitors produce those tissues and how articular cartilage acquires its functional postnatal organization characterized by chondrocyte columns, zone-specific cell volumes and anisotropic matrix. Using novel Gdf5CreERT2 (Gdf5-CE), Prg4-CE and Dkk3-CE mice mated to R26-Confetti or single-color reporters, we found that knee joint progenitors produced small non-migratory progenies and distinct local tissues over prenatal and postnatal time. Stereological imaging and quantification indicated that the columns present in juvenile-adult tibial articular cartilage consisted of non-daughter, partially overlapping lineage cells, likely reflecting cell rearrangement and stacking. Zone-specific increases in cell volume were major drivers of tissue thickening, while cell proliferation or death played minor roles. Second harmonic generation with 2-photon microscopy showed that the collagen matrix went from being isotropic and scattered at young stages to being anisotropic and aligned along the cell stacks in adults. Progenitor tracing at prenatal or juvenile stages showed that joint injury provoked a massive and rapid increase in synovial Prg4+ and CD44+/P75+ cells some of which filling the injury site, while neighboring chondrocytes appeared unresponsive. Our data indicate that local cell populations produce distinct joint tissues and that articular cartilage growth and zonal organization are mainly brought about by cell volume expansion and topographical cell rearrangement. Synovial Prg4+ lineage progenitors are exquisitely responsive to acute injury and may represent pioneers in joint tissue repair.

Osteophyte formation and matrix mineralization in a TMJ osteoarthritis mouse model are associated with ectopic hedgehog signaling.

The temporomandibular joint (TMJ) is a diarthrodial joint that relies on lubricants for frictionless movement and long-term function. It remains unclear what temporal and causal relationships may exist between compromised lubrication and onset and progression of TMJ disease. Here we report that Proteoglycan 4 (Prg4)-null TMJs exhibit irreversible osteoarthritis-like changes over time and are linked to formation of ectopic mineralized tissues and osteophytes in articular disc, mandibular condyle and glenoid fossa. In the presumptive layer of mutant glenoid fossa's articulating surface, numerous chondrogenic cells and/or chondrocytes emerged ectopically within the type I collagen-expressing cell population, underwent endochondral bone formation accompanied by enhanced Ihh expression, became entrapped into temporal bone mineralized matrix, and thereby elicited excessive chondroid bone formation. As the osteophytes grew, the roof of the glenoid fossa/eminence became significantly thicker and flatter, resulting in loss of its characteristic concave shape for accommodation of condyle and disc. Concurrently, the condyles became flatter and larger and exhibited ectopic bone along their neck, likely supporting the enlarged condylar heads. Articular discs lost their concave configuration, and ectopic cartilage developed and articulated with osteophytes. In glenoid fossa cells in culture, hedgehog signaling stimulated chondrocyte maturation and mineralization including alkaline phosphatase, while treatment with hedgehog inhibitor HhAntag prevented such maturation process. In sum, our data indicate that Prg4 is needed for TMJ integrity and long-term postnatal function. In its absence, progenitor cells near presumptive articular layer and disc undergo ectopic chondrogenesis and generate ectopic cartilage, possibly driven by aberrant activation of Hh signaling. The data suggest also that the Prg4-null mice represent a useful model to study TMJ osteoarthritis-like degeneration and clarify its pathogenesis.