Evaluation of the Sustainability of an Intervention to Increase HIV Testing

BACKGROUND Sustainability—the routinization and institutionalization of processes that improve the quality of healthcare—is difficult to achieve and not often studied. OBJECTIVE To evaluate the sustainability of increased rates of HIV testing after implementation of a multi-component intervention in two Veterans Health Administration healthcare systems. DESIGN Quasi-experimental implementation study in which the effect of transferring responsibility to conduct the provider education component of the intervention from research to operational staff was assessed. PATIENTS Persons receiving healthcare between 2005 and 2006 (intervention year) and 2006 and 2007 (sustainability year). MEASUREMENTS Monthly HIV testing rate, stratified by frequency of clinic visits RESULTS The monthly adjusted testing rate increased from 2% at baseline to 6% at the end intervention year and then declined reaching 4% at the end of the sustainability year. However, the stratified, visit-specific testing rate for persons newly exposed to the intervention (i.e., having their first through third visits during the study period) increased throughout the intervention and sustainability years. Increases in the proportion of visits by patients who remained untested despite multiple, prior exposures to the intervention accounted for the aggregate attenuation of testing during the sustainability year. Overall, the percentage of patients who received an HIV test in the sustainability year was 11.6%, in the intervention year 11.1%, and in the pre-intervention year 5.0% CONCLUSIONS Provider education combined with informatics and organizational support had a sustainable effect on HIV testing rates. The effect was most pronounced during patients' early contacts with the healthcare system.Health Services Research & Development Service (SDP 06–001

Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial

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The building up of the disk galaxy M33 and the evolution of the metallicity gradient

The evolution of radial gradients of metallicity in disk galaxies and its relation with the disk formation are not well understood. Theoretical models of galactic chemical evolution make contrasting predictions about the time evolution of metallicity gradients. To test chemical evolution models and trace the star formation and accretion history of low luminosity disk galaxies we focus on the Local Group galaxy M33. We analyze O/H and S/H abundances in planetary nebulae, H{\sc ii} regions, and young stars, together with known [Fe/H] abundances in the old stellar population of M33. With a theoretical model, we follow the time evolution of gas (diffuse and condensed in clouds), stars, and chemical abundances in the disk of M33, assuming that the galaxy is accreting gas from an external reservoir. Our model is able to reproduce the available observational constraints on the distribution of gas and stars in M33 and to predict the time evolution of several chemical abundances. In particular, we find that a model characterized by a continuous infall of gas on the disk, at a rate of $\dot M_{\rm inf}\approx 1$ $M_\odot$ yr$^{-1}$, almost constant with time, can also account for the relatively high rate of star formation and for the shallow chemical gradients. Supported by a large sample of high resolution observations for this nearby galaxy, we conclude that the metallicity in the disk of M33 has increased with time at all radii, with a continuous flattening of the gradient over the last $\sim 8$ Gyr.Comment: 16 pages, 11 figures, A&A accepte

The evolution of the Galactic metallicity gradient from high-resolution spectroscopy of open clusters

Open clusters offer a unique possibility to study the time evolution of the radial metallicity gradients of several elements in our Galaxy, because they span large intervals in age and Galactocentric distance, and both quantities can be more accurately derived than for field stars. We re-address the issue of the Galactic metallicity gradient and its time evolution by comparing the empirical gradients traced by a sample of 45 open clusters with a chemical evolution model of the Galaxy. At variance with previous similar studies, we have collected from the literature only abundances derived from high--resolution spectra. The clusters have distances $7 < RGC<22$ kpc and ages from $\sim 30$ Myr to 11 Gyr. We also consider the $\alpha$-elements Si, Ca, Ti, and the iron-peak elements Cr and Ni. The data for iron-peak and $\alpha$-elements indicate a steep metallicity gradient for R_GC<12$kpc and a plateau at larger radii. The time evolution of the metallicity distribution is characterized by a uniform increase of the metallicity at all radii, preserving the shape of the gradient, with marginal evidence for a flattening of the gradient with time in the radial range 7-12 kpc. Our model is able to reproduce the main features of the metallicity gradient and its evolution with an infall law exponentially decreasing with radius and with a collapse time scale of the order of 8 Gyr at the solar radius. This results in a rapid collapse in the inner regions, i.e.$R_{\rm GC}\lesssim 12$ kpc (that we associate with an early phase of disk formation from the collapse of the halo) and in a slow inflow of material per unit area in the outer regions at a constant rate with time.Comment: 16 pages, 18 figures, A&A accepte

Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer

BACKGROUND The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known. METHODS We performed a prospective trial involving 9427 women with hormone-receptor–positive, human epidermal growth factor receptor 2–negative, axillary node–negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger. RESULTS The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≤1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%). CONCLUSIONS Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy

Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer

BACKGROUND The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. METHODS We performed a prospective trial involving 10,273 women with hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, axillary node–negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease–free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death). RESULTS Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease–free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P=0.26). At 9 years, the two treatment groups had similar rates of invasive disease–free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local–regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for invasive disease–free survival varied with the combination of recurrence score and age (P=0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. CONCLUSIONS Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor–positive, HER2-negative, axillary node–negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger

A step towards personalizing next line therapy for resected pancreatic and related cancer patients: A single institution\u27s experience

Background: There is a lack of precision medicine in pancreatic ductal adenocarcinoma (PDA) and related cancers, and outcomes for patients with this diagnosis remain poor despite decades of research investigating this disease. Therefore, it is necessary to explore novel therapeutic options for these patients who may benefit from personalized therapies. Objective: Molecular profiling of hepatopancreaticobiliary malignancies at our institution, including but not limited to PDA, was initiated to assess the feasibility of incorporating molecular profiling results into patient oncological therapy planning. Methods: All eligible patients from Thomas Jefferson University (TJU) with hepatopancreaticobiliary tumors including PDA, who agreed to molecular testing profiling, were prospectively enrolled in a registry study from December 2014 to September 2017 and their tumor samples were tested to identify molecular markers that can be used to guide therapy options in the future. Next generation sequencing (NGS) and protein expression in tumor samples were tested at CLIA-certified laboratories. Prospective clinicopathologic data were extracted from medical records and compiled in a de-identified fashion. Results: Seventy eight (78) patients were enrolled in the study, which included 65/78 patients with PDA (local and metastatic) and out of that subset, 52/65 patients had surgically resected PDA. Therapy recommendations were generated based on molecular and clinicopathologic data for all enrolled patients. NGS uncovered actionable alterations in 25/52 surgically resected PDAs (48%) which could be used to guide therapy options in the future. High expression of three proteins, TS (p = 0.005), ERCC1 (p = 0.001), and PD-1 (p = 0.04), was associated with reduced recurrence-free survival (RFS), while TP53 mutations were correlated with longer RFS (p = 0.01). Conclusions: The goal of this study was to implement a stepwise strategy to identify and profile resected PDAs at our institution. Consistent with previous studies, approximately half of patients with resected PDA harbor actionable mutations with possible targeted therapeutic implications. Ongoing studies will determine the clinical value of identifying these mutations in patients with resected PDA