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Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2− ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study (NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. Methods: This retrospective chart review included women with HR+/HER2− ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan–Meier analysis. Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.  相似文献   
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Objective

To determine whether differences in combination DTaP vaccine types at 2, 4 and 6?months of age were associated with mortality (all-cause or non-specific), within 30?days of vaccination.

Design

Observational nationwide cohort study.

Setting

Linked population data from the Australian Childhood Immunisation Register and National Death Index.

Participants

Australian infants administered a combination trivalent, quadrivalent or hexavalent DTaP vaccine (DTaP types) between January 1999 and December 2010 at 2, 4 and 6?months as part of the primary vaccination series. The study population included 2.9, 2.6, & 2.3?million children in the 2, 4 and 6?month vaccine cohorts, respectively.

Main outcome measures

Infants were evaluated for the primary outcome of all-cause mortality within 30?days. A secondary outcome was non-specific mortality (unknown cause of death) within 30?days of vaccination. Non-specific mortality was defined as underlying or other cause of death codes, R95 ‘Sudden infant death syndrome’, R96 ‘Other sudden death, cause unknown’, R98 ‘Unattended death’, R99 ‘Other ill-defined and unspecified cause of mortality’ or where no cause of death was recorded.

Results

The rate of 30?day all-cause mortality was low and declined from 127.4 to 59.3 deaths per 100,000 person-years between 2 and 6?month cohorts. When compared with trivalent DTaP vaccines, no elevated risk in all-cause or non-specific mortality was seen with any quadrivalent or hexavalent DTaP vaccines, for any cohort.

Conclusion

Use of routine DTaP combination vaccines with differing disease antigens administered during the first six months of life is not associated with infant mortality.  相似文献   
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alpha 2-Adrenergic receptors (ARs) are involved in central nervous system (CNS) control of blood pressure. It is now known that there are three human genes that encode subtypes of alpha 2-ARs, but little is known regarding the distribution of these subtypes throughout the CNS. The availability of receptor clones allows the mapping of mRNAs encoding the individual alpha 2-AR subtypes in the CNS. In this communication, we report that there are three, closely related rat alpha 2-AR genes. We have developed subtype-specific hybridization probes from each of these genes and have used these reagents to measure alpha 2-AR subtype mRNA accumulation in extracts of discrete regions of the rat CNS. We found that mRNAs encoding the alpha 2A-AR and alpha 2C-AR subtypes are distributed widely, but unevenly, throughout the rat CNS. The A subtype is prominent in the midbrain, brainstem, spinal cord, pituitary and diencephalon while the C subtype predominates in basal ganglia and cerebellum. The cortex, olfactory bulb and hippocampus contain roughly equal amounts of the alpha 2A- and alpha 2C-AR mRNAs. A third subtype's (alpha 2B-AR) mRNA is far less abundant in brain tissues, and is only found in the diencephalon.  相似文献   
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Extensor mechanism complications following total knee arthroplasty   总被引:5,自引:0,他引:5  
Extensor mechanism complications following 281 knee arthroplasties that included patellar resurfacing, performed by two surgeons in one hospital over a 6-year period, were reviewed. The mean follow-up period was 42 months. There were 28 (10%) extensor mechanism complications: 3 quadriceps tendon ruptures, 5 patellar fractures, 4 patellar tendon ruptures, 11 recurring patellar subluxations, 4 cases of patellar pain, and 1 malrotated patella. Nine (3%) required further surgery. Surgical technique may have contributed to the tendon ruptures; patellar fractures occurred mainly in patients who had rheumatoid arthritis. Patients with patellar subluxation had abnormal preoperative valgus deformities of their knees and presented with this subluxation problem an average of 4 months after surgery, but it appeared to cause them less discomfort with time. Patellar resurfacing as part of a knee arthroplasty procedure is recommended but should be performed with care to the integrity and vasculature of the extensor mechanism.  相似文献   
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