The impact of primary care practices adopting the patient-centered medical home (PCMH) model is analyzed by comparing per member per month (PMPM) costs and utilization among commercial HMO members ...with chronic illnesses in PCMH and non-PCHM practices in the Philadelphia area. Transforming primary care practices to conform to the PCMH model has shown early promise in reducing costs and improving outcomes, and chronically ill patients' frequent contact with the healthcare system and costly care make them ideal targets for such health system reforms.
The impact of the PCMH model on PMPM costs was analyzed using a generalized linear regression model to adjust for age, gender, and baseline cost. The impact of the PCMH model on utilization per 1000 rates was analyzed with the Poisson regression model, adjusting for baseline differences in age, gender, and risk score.
After accounting for differences at baseline, PCMH practices achieved lower total, inpatient, and specialist PMPM costs, as well as lower relative utilization of hospital admissions and specialist visits.
These findings suggest that policy makers should maintain or expand incentives to adopt PCMH reforms and that targeting chronically ill patients may be the most effective way to leverage the benefits of PCMH adoption.
C/EBPs are a family of B-Zip transcription factors--TFs--involved in the regulation of differentiation in several tissues. The two most studied members--C/EBPα and C/EBPβ--play important roles in ...skin homeostasis and their ablation reveals cells with stem cells signatures. Much less is known about C/EBPδ which is highly expressed in the granular layer of interfollicular epidermis and is a direct target of p63, the master regular of multilayered epithelia. We identified C/EBPδ target genes in human primary keratinocytes by ChIP on chip and profiling of cells functionally inactivated with siRNA. Categorization suggests a role in differentiation and control of cell-cycle, particularly of G2/M genes. Among positively controlled targets are numerous genes involved in barrier function. Functional inactivation of C/EBPδ as well as overexpressions of two TF targets--MafB and SOX2--affect expression of markers of keratinocyte differentiation. We performed IHC on skin tumor tissue arrays: expression of C/EBPδ is lost in Basal Cell Carcinomas, but a majority of Squamous Cell Carcinomas showed elevated levels of the protein. Our data indicate that C/EBPδ plays a role in late stages of keratinocyte differentiation.
Purpose
We have evaluated thoracic conformation of patients in order to derive a numeric value predictive of an increased dose to left anterior descending coronary artery (LAD), critical structure ...for the development of late radio induced cardiac morbidity.
Methods
We have evaluated 91 patients (36–88 years) affected by breast cancer stage I–II (Tis–T1–2 N0–1), undergoing adjuvant radiotherapy with conventional fractionation. For each patient on CT images was measured the distance between the back face of the sternum (manubrium) and the anterior face of body of the corresponding vertebra (a), and the distance measured on the line at 45° between the vertebral body of the same vertebra and the back face of the rib corresponding (b). The a/b ratio showed values between 0.626 and 1.123. We used the median value (0.821) as cut-off to divide the patients in two groups. We calculated in both groups: Volume (Vol) heart, Vol LAD with an expansion of 0.6 mm; Dmean LAD (Gy); Dmax LAD (Gy); V10–V20–V30 (%) LAD and we correlated these values with parametric and non-parametric tests.
Results
The Pearson test has showed a statistically significant correlation between Vol breast and V10, V20, V30 with borderline significance (p = 0.006; p = 0.02; p = 0.05). The data were confirmed by testing non-parametric Kendall (tau = 0.004; tau = 0.015; tau = 0.016) and Spearman (rho = 0.003; rho = 0.016; rho = 0.015). We conducted categorizing into quartiles of breast volume and evaluated the correlation with a/b. We have found a significative correlation (p = 0.01) between small Vol breast (≤660.23 cc) and a/b < 0.0821 and greater Vol breast (>660.23 cc) with a/b > 0.0821. From the evaluation of the distribution of V10 in the two groups taking account of the Dmean ≤5 or >5 significance was found with a/b; Chi square 0.009 (0.01). Values ≤5 were observed in women with a/b < 0.0821. Values >5 in women with a/b > 0.0821.
Conclusions
The geometric conformity of chest thorax considering a/b and the value of 0.0821 can reveals an important parameter in the selection of patients suitable for radiation therapy on left breast in order to evaluate the risk of late cardiac events. This consideration during treatment planning can change the technique or the set-up allowing the development of a customized plan.
Microarray experiments enable simultaneous measurement of the expression levels of virtually all transcripts present in cells, thereby providing a 'molecular picture' of the cell state. On the other ...hand, the genomic responses to a pharmacological or hormonal stimulus are dynamic molecular processes, where time influences gene activity and expression. The potential use of the statistical analysis of microarray data in time series has not been fully exploited so far, due to the fact that only few methods are available which take into proper account temporal relationships between samples.
We compared here four different methods to analyze data derived from a time course mRNA expression profiling experiment which consisted in the study of the effects of estrogen on hormone-responsive human breast cancer cells. Gene expression was monitored with the innovative Illumina BeadArray platform, which includes an average of 30-40 replicates for each probe sequence randomly distributed on the chip surface. We present and discuss the results obtained by applying to these datasets different statistical methods for serial gene expression analysis. The influence of the normalization algorithm applied on data and of different parameter or threshold choices for the selection of differentially expressed transcripts has also been evaluated. In most cases, the selection was found fairly robust with respect to changes in parameters and type of normalization. We then identified which genes showed an expression profile significantly affected by the hormonal treatment over time. The final list of differentially expressed genes underwent cluster analysis of functional type, to identify groups of genes with similar regulation dynamics.
Several methods for processing time series gene expression data are presented, including evaluation of benefits and drawbacks of the different methods applied. The resulting protocol for data analysis was applied to characterization of the gene expression changes induced by estrogen in human breast cancer ZR-75.1 cells over an entire cell cycle.
ABSTRACT
Radiotherapy is crucial in the management of cancer patients in both the curative and palliative settings. However, patients often report pain both during positioning for, and execution of, ...radiotherapy and this may be a reason for interrupting the radiotherapy session. This observation is common even if the patient is undergoing baseline drug therapy for cancer pain. Recent data suggest that orally administrated immediate-release morphine (MIR) is able to reduce pain in patients with predictable pain. The authors tested a rescue dose of MIR 10 or 20 mg, 20 to 60 minutes before radiotherapy, to verify the effectiveness of MIR in this setting and also to assess the patient's ability to receive the full course of radiotherapy. One hundred forty consecutive patients were evaluated during radiotherapy treatment and visual analogue scale (VAS) and positioning VAS scores were assessed. All patients completed the course of scheduled radiotherapy and pain was well controlled, despite the fact that previous pharmacological treatment had not been able to completely control chronic cancer pain. These data strongly suggest a role for MIR pretreatment in patients with pain due to positioning during radiotherapy.
The clinical benefits of postoperative radiation therapy (PORT) for patients with thymoma are still controversial. In the absence of defined guidelines, prognostic factors such as stage, status of ...surgical margins, and histology are often considered to guide the choice of adjuvant treatment (radiotherapy and/or chemotherapy). In this study, we describe our single-institution experience of three-dimensional conformal PORT administered as adjuvant treatment to patients with thymoma.
Twenty-two consecutive thymoma patients (eleven male and eleven female) with a median age of 52 years and treated at our institution by PORT were analyzed. The patients were considered at high risk of recurrence, having at least one of the following features: stage IIB or III, involved resection margins, or thymic carcinoma histology. Three-dimensional conformal PORT with a median total dose on clinical target volume of 50 (range 44-60) Gy was delivered to the tumor bed by 6-20 MV X-ray of the linear accelerator. Follow-up after radiotherapy was done by computed tomography scan every 6 months for 2 years and yearly thereafter.
Two of the 22 patients developed local recurrence and four developed distant metastases. Median overall survival was 100 months, and the 3-year and 5-year survival rates were 83% and 74%, respectively. Median disease-free survival was 90 months, and the 5-year recurrence rate was 32%. On univariate analysis, pathologic stage III and presence of positive surgical margins had a significant impact on patient prognosis. Radiation toxicity was mild in most patients and no severe toxicity was registered.
Adjuvant radiotherapy achieved good local control and showed an acceptable toxicity profile in patients with high-risk thymoma.
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