Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Michaelson MD,McKay RR,Werner L,Atkins MB,Van Allen EM,Olivier KM,Song J,Signoretti S,McDermott DF,Choueiri TK.Cancer. 2015 Oct 1;121(19):3435-43. [Epub 2015 Jun 8]. doi: 10.1002/cncr.29503.

Background

Sarcomatoid renal cell carcinoma (RCC) is associated with an aggressive biology and a poor prognosis. Poor-risk RCC is defined by clinical prognostic factors and demonstrates similarly aggressive behavior. No standard treatment exists for patients with sarcomatoid RCC, and treatment options for patients with poor-risk disease are of limited benefit. The objective of this study was to investigate the efficacy of antiangiogenic therapy in combination with cytotoxic chemotherapy in clinically aggressive RCC.

Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral‐naïve patients

Objectives

The aim of the study was to determine whether the incidence of first‐line treatment discontinuations and their causes changed according to the time of starting highly active antiretroviral therapy (HAART) in an Italian cohort.

Methods

We included in the study patients from the Italian COhort Naïve Antiretrovirals (ICoNA) who initiated HAART when naïve to antiretroviral therapy (ART). The endpoints were discontinuation within the first year of ≥1 drug in the first HAART regimen for any reason, intolerance/toxicity, poor adherence, immunovirological/clinical failure and simplification. We investigated whether the time of starting HAART (stratified as ‘early’, 1997–1999; ‘intermediate’, 2000–2002; ‘recent’, 2003–2007) was associated with the probability of reaching the endpoints by a survival analysis.

Results

Overall, the 1‐year probability of discontinuation of ≥1 drug in the first regimen was 36.1%. The main causes of discontinuation were intolerance/toxicity (696 of 1189 patients; 58.5%) and poor adherence (285 of 1189 patients; 24%). The hazards for all‐reason change were comparable according to calendar period [2000–2002, adjusted relative hazard (ARH) 0.82, 95% confidence interval (CI) 0.69–0.98; 2003–2007, ARH 0.94, 95% CI 0.76–1.16, vs. 1997–1999; global P‐value=0.08]. Patients who started HAART during the ‘recent’ period were less likely to change their initial regimen because of intolerance/toxicity (ARH 0.67, 95% CI 0.51–0.89 vs. ‘early’ period). Patients who started in the ‘intermediate’ and ‘recent’ periods had a higher risk of discontinuation because of simplification (ARH 15.26, 95% CI 3.21–72.45, and ARH 37.97, 95% CI 7.56–190.64, vs. ‘early’ period, respectively).

Conclusions

It seems important to evaluate reason‐specific trends in the incidence of discontinuation in order to better understand the determinants of changes over time. The incidence of discontinuation because of intolerance/toxicity has declined over time while simplification strategies have become more frequent in recent years. Intolerance/toxicity remains the major cause of drug discontinuation.     

Effect of lifestyle intervention for people with diabetes or prediabetes in real-world primary care: propensity score analysis

Background

It is important to keep the level of antibiotic prescribing low to contain the development of resistant bacteria. This study was conducted to reveal new knowledge about how GPs think in relation to the prescribing of antibiotics - knowledge that could be used in efforts toward rational treatment of infectious diseases in primary care. The aim was to explore and describe the variations in GPs' perceptions of infectious disease management, with special reference to antibiotic prescribing.

Methods

Twenty GPs working at primary care centres in a county in south-west Sweden were purposively selected based on the strategy of including GPs with different kinds of experience. The GPs were interviewed and perceptions among GPs were analysed by a phenomenographic approach.

Results

Five qualitatively different perceptions of infectious disease management were identified. They were: (A) the GP must help the patient to achieve health and well-being; (B) the management must meet the GP's perceived personal, professional and organisational demands; (C) restrictive antibiotic prescribing is time-consuming; (D) restrictive antibiotic prescribing can protect the effectiveness of antibiotics; and (E) patients benefit personally from restrictive antibiotic prescribing.

Conclusions

Restrictive antibiotic prescribing was considered important in two perceptions, was not an issue as such in two others, and was considered in one perception although the actual prescribing was greatly influenced by the interaction between patient and GP. Accordingly, to encourage restrictive antibiotic prescribing several aspects must be addressed. Furthermore, different GPs need various kinds of support. Infectious disease management in primary care is complex and time-consuming, which must be acknowledged in healthcare organisation and planning.     

The segmental organization of the developing shark brain based on neurochemical markers, with special attention to the prosencephalon

Brain regionalization has been extensively studied in tetrapods, teleosts and cyclostomes. In contrast, it has not been investigated in elasmobranchs, despite their key phylogenetic position to understand brain evolution in jawed vertebrates. In this study we provide a schematic view of the segmental pattern of the developing shark brain based on mapping of the expression of Pax6 and neurochemical markers such as calretinin, tyrosine hydroxylase, serotonin, and glutamic acid decarboxylase. By correlating the cytoarchitectonic limits with the specific location of these markers, we identify transverse and longitudinal boundaries and domains, which suggest a segmental pattern, reminiscent of the one described in other vertebrates. Taken together, these data provide an initial scheme, which will be further tested and refined using a broader range of genetic markers involved in patterning and differentiation.