Challenges and Opportunities to Updating Prescribing Information for Longstanding Oncology Drugs.

A number of important drugs used to treat cancer-many of which serve as the backbone of modern chemotherapy regimens-have outdated prescribing information in their drug labeling. The Food and Drug Administration is undertaking a pilot project to develop a process and criteria for updating prescribing information for longstanding oncology drugs, based on the breadth of knowledge the cancer community has accumulated with the use of these drugs over time. This article highlights a number of considerations for labeling updates, including selecting priorities for updating; data sources and evidentiary criteria; as well as the risks, challenges, and opportunities for iterative review to ensure prescribing information for oncology drugs remains relevant to current clinical practice

Determinants of the number of mammography units in 31 countries with significant mammography screening

In the 2000s, most of the female population of industrialised countries had access to mammography breast cancer screening, but with variable modalities among the countries. We assessed the number of mammography units (MUs) in 31 European, North American and Asian countries where significant mammography activity has existed for over 10 years, collecting data on the number of such units and of radiologists by contacting institutions in each country likely to provide the relevant information. Around 2004, there were 32 324 MU in 31 countries, the number per million women ranging from less than 25 in Turkey, Denmark, the Netherlands, the United Kingdom, Norway, Poland and Hungary to more than 80 in Cyprus, Italy, France, the United States and Austria. In a multivariate analysis, the number of MUs was positively associated with the number of radiologists (P=0.0081), the number of women (P=0.0023) and somewhat with the country surface area (P=0.077). There is considerable variation in the density of MU across countries and the number of MUs in service are often well above what would be necessary according to local screening recommendations. High number of MUs in some countries may have undesirable consequences, such as unnecessarily high screening frequency and decreased age at which screening is started

Methods for the Watch the Spot Trial. A Pragmatic Trial of More- versus Less-Intensive Strategies for Active Surveillance of Small Pulmonary Nodules.

Small pulmonary nodules are most often managed by surveillance imaging with computed tomography (CT) of the chest, but the optimal frequency and duration of surveillance are unknown. The Watch the Spot Trial is a multicenter, pragmatic, comparative-effectiveness trial with cluster randomization by hospital or health system that compares more- versus less-intensive strategies for active surveillance of small pulmonary nodules. The study plans to enroll approximately 35,200 patients with a small pulmonary nodule that is newly detected on chest CT imaging, either incidentally or by screening. Study protocols for more- and less-intensive surveillance were adapted from published guidelines. The primary outcome is the percentage of cancerous nodules that progress beyond American Joint Committee on Cancer seventh edition stage T1a. Secondary outcomes include patient-reported anxiety and emotional distress, nodule-related health care use, radiation exposure, and adherence with the assigned surveillance protocol. Distinctive aspects of the trial include: 1) the pragmatic integration of study procedures into existing clinical workflow; 2) the use of cluster randomization by hospital or health system; 3) the implementation and evaluation of a system-level intervention for protocol-based care; 4) the use of highly efficient, technology-enabled methods to identify and (passively) enroll participants; 5) reliance on data collected as part of routine clinical care, including data from electronic health records and state cancer registries; 6) linkage with state cancer registries for complete ascertainment of the primary study outcome; and 7) intensive engagement with a diverse group of patient and nonpatient stakeholders in the design and execution of the study

Surveillance for endometrial cancer with transvaginal ultrasonography of breast cancer patients under tamoxifen treatment

The association of endometrial thickness with the risk of developing endometrial cancer (EC) within 2 years was investigated in a consecutive cohort of 1205 breast cancer patients under tamoxifen treatment, undergoing transvaginal ultrasonography (TVUS) for follow-up purpose (asymptomatic, 1068) or for abnormal uterine bleeding (AUB, 137). Linkage with tumour registry allowed for the follow-up of 3184.3 person-years. According to underlying incidence, 1.85 EC cases were expected in the study cohort while 12 were observed (observed/expected ratio=6.49, 95% CI 3.35–11.33; asymptomatic=4.09, 95% CI 1.65–8.43, symptomatic=35.71, 95% CI 11.59–83.34). No EC was observed with thickness (half layer) <3 mm. Raising this threshold increased specificity with a substantial loss of sensitivity (⩾3, ⩾4, ⩾6, ⩾9 mm; spec.=25.8, 44.5, 76.1, 91.5%, sens.=100, 91.6, 75.0, 66.6%). The presence of AUB was rather specific (88.94%) but poorly sensitive (41.67%). A combination of AUB presence/absence and thickness allowed the best accuracy (AUB + thickness ⩾3, ⩾4 or ⩾5; sens.=100, 81.6 or 91.6%; spec.=22.8, 40.4, or 56.7%). Breast cancer patients under tamoxifen might be selected for further invasive assessment on the basis of AUB and endometrial thickness assessed at TVUS

Mammography Facility Characteristics Associated With Interpretive Accuracy of Screening Mammography

BackgroundAlthough interpretive performance varies substantially among radiologists, such variation has not been examined among mammography facilities. Understanding sources of facility variation could become a foundation for improving interpretive performance.MethodsIn this cross-sectional study conducted between 1996 and 2002, we surveyed 53 facilities to evaluate associations between facility structure, interpretive process characteristics, and interpretive performance of screening mammography (ie, sensitivity, specificity, positive predictive value [PPV1], and the likelihood of cancer among women who were referred for biopsy [PPV2]). Measures of interpretive performance were ascertained prospectively from mammography interpretations and cancer data collected by the Breast Cancer Surveillance Consortium. Logistic regression and receiver operating characteristic (ROC) curve analyses estimated the association between facility characteristics and mammography interpretive performance or accuracy (area under the ROC curve [AUC]). All P values were two-sided.ResultsOf the 53 eligible facilities, data on 44 could be analyzed. These 44 facilities accounted for 484 463 screening mammograms performed on 237 669 women, of whom 2686 were diagnosed with breast cancer during follow-up. Among the 44 facilities, mean sensitivity was 79.6% (95% confidence interval [CI] = 74.3% to 84.9%), mean specificity was 90.2% (95% CI = 88.3% to 92.0%), mean PPV1 was 4.1% (95% CI = 3.5% to 4.7%), and mean PPV2 was 38.8% (95% CI = 32.6% to 45.0%). The facilities varied statistically significantly in specificity (P &lt; .001), PPV1 (P &lt; .001), and PPV2 (P = .002) but not in sensitivity (P = .99). AUC was higher among facilities that offered screening mammograms alone vs those that offered screening and diagnostic mammograms (0.943 vs 0.911, P = .006), had a breast imaging specialist interpreting mammograms vs not (0.932 vs 0.905, P = .004), did not perform double reading vs independent double reading vs consensus double reading (0.925 vs 0.915 vs 0.887, P = .034), or conducted audit reviews two or more times per year vs annually vs at an unknown frequency (0.929 vs 0.904 vs 0.900, P = .018).ConclusionMammography interpretive performance varies statistically significantly by facility

Overdiagnosis and overtreatment of breast cancer: Rates of ductal carcinoma in situ: a US perspective

The incidence of breast ductal carcinoma in situ (DCIS) in the USA exceeds that of other countries. This cannot be explained entirely by the frequency of mammographic screening in the USA and may result from differences in the interpretation of mammograms and/or the frequency with which biopsies are obtained. Although the percentage of DCIS patients treated with mastectomy has decreased, the absolute number is unchanged and the use of lumpectomy with whole-breast radiotherapy has increased in inverse proportion to the decrease in mastectomy. Treatment of DCIS with tamoxifen is still limited

Contemporary changes and civil society in Portugal and the Russian Federation

Portugal and the Russian Federation share some aspects of traditional culture and similar experiences in modern history, but they also exhibit significant differences that determine specific modes of civil society’s development. Results of a comparative and diachronic analysis show that the major differences between the two countries reside in civil society’s openness and composition. Organized civil society is not very distinct in relative size when comparing Portugal and the Russian Federation, but it is globally more autonomous, expressive, trusted and institutionalized in Portugal than in the Russian Federation and among the factors that contribute to this condition are an earlier and revolutionary transition to democracy, a larger middle class, a greater prevalence of the value of interdependence, and a regime that endorses bigger public social expenditure in Portugal, all this within the framework of the European Union that has a longer history of social demand and institutional incentives for civil society. Despite those unequal conditions, civil society faces similar current challenges in both countries, mainly with the outsourcing of the public provision of social services.info:eu-repo/semantics/acceptedVersio

Relaxing learned constraints through cathodal tDCS on the left dorsolateral prefrontal cortex

We solve problems by applying previously learned rules. The dorsolateral prefrontal cortex (DLPFC) plays a pivotal role in automating this process of rule induction. Despite its usual efficiency, this process fails when we encounter new problems in which past experience leads to a mental rut. Learned rules could therefore act as constraints which need to be removed in order to change the problem representation for producing the solution. We investigated the possibility of suppressing the DLPFC by transcranial direct current stimulation (tDCS) to facilitate such representational change. Participants solved matchstick arithmetic problems before and after receiving cathodal, anodal or sham tDCS to the left DLPFC. Participants who received cathodal tDCS were more likely to solve the problems that require the maximal relaxation of previously learned constraints than the participants who received anodal or sham tDCS. We conclude that cathodal tDCS over the left DLPFC might facilitate the relaxation of learned constraints, leading to a successful representational change

General practitioners' evaluation of community psychiatric services: responsiveness to change of the General Practitioner Experiences Questionnaire (GPEQ)

<p>Abstract</p> <p>Background</p> <p>Instruments have been developed to assess professional views of the quality of care but have rarely been tested for responsiveness to change. The objective of this study was to test the responsiveness of the General Practitioner Experiences Questionnaire (GPEQ) for the measurement of Community Mental Health Centres in Norway.</p> <p>Methods</p> <p>National surveys were conducted in Norway in 2006 (n = 2,415) and 2008 (n = 2,209) to measure general practitioners' evaluation of community mental health centres. GPs evaluated the centres by means of a postal questionnaire, consisting of questions focused on centre quality and cooperation with GPs. As part of the national surveys 75 GPs in 2006 and 66 GPs in 2008 evaluated Hamar community mental health centre. Between the surveys, several quality improvement initiatives were implemented which were directed at cooperation with and guidance for GPs in Stange municipality, one of eight municipalities in Hamar centre catchment area. The main outcome measures were changes in GPEQ scores from 2006 to 2008 for GPs evaluating Hamar community mental health centre from Stange municipality, and changes in scores for GPs in the other seven municipalities and nationally which were assessed for statistical significance.</p> <p>Results</p> <p>GPs in Stange municipality rated Hamar community mental health centre significantly better on the guidance scale in 2008 than in 2006; on a 0-100 scale where 100 represents the best possible experiences the score was 26.5 in 2006 and 58.3 in 2008 (p < 0.001). Apart from one item about workforce situation, none of the other scales and items showed significant changes. The control group from the other seven municipalities gave significantly poorer rating for the emergency situation scale, the workforce situation scale and seven items in 2008 than in 2006. The national results showed small differences between 2006 and 2008, even though several scales and items were significantly different. A question about changes in centre performance over the last 2-3 years showed that 82% of GPs from Stange municipality reported that Hamar community mental health centre had improved, compared to only 36% from the other seven municipalities and 40% nationally which was statistically significant.</p> <p>Conclusions</p> <p>Following the implementation of an initiative designed to enhance service quality, the GPEQ identified expected changes in the guidance scale for the intervention group, indicating that the instrument is responsive to change. The worsening of services for GPs in the control group evaluating Hamar centre warrants further study.</p