53 research outputs found
Concomitant sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman Disease) and diffuse large B-cell lymphoma: a case report
IntroductionSinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman Disease, is a rare and benign source of lymphadenopathy first described in 1969, which mimics neoplastic processes. This disease commonly presents in children and young adults with supra-diaphragmatic lymphadenopathy or extranodal lesions consisting of tissue infiltrates composed of a polyclonal population of histiocytes. Since its description greater than 400 cases have been described, sometimes in patients with a variety of treated and untreated neoplastic diseases. However, the literature contains reports of only 19 cases of Rosai-Dorfman Disease in association with lymphomas, Hodgkin's or non-Hodgkin's. The majority of these cases have the two diagnoses, malignant lymphoma and Rosai-Dorfman Disease, separated in time. Interestingly, infradiaphragmatic lymphadenopathy was a feature in the majority of previously reported cases of Rosai-Dorfman Disease and non-Hodgkin's lymphoma.Case presentationThis report provides details of a case with co-existing sinus histiocytosis with massive lymphadenopathy and diffuse large B cell non-Hodgkin's lymphoma. This case is the fifth described case of simultaneous Rosai-Dorfman Disease and concurrent non-Hodgkin's lymphoma. Unfortunately, the diagnosis of a clinically aggressive diffuse large B cell lymphoma was made at autopsy. The aggressive biological behavior of the diffuse large B cell lymphoma in this patient may have been related to the underlying immune dysregulation believed to be part of the pathophysiology of Rosai-Dorfman Disease.ConclusionTaken together this report and the preceding reports of Rosai-Dorfman Disease and non-Hodgkin's lymphoma suggests that in cases with a diagnosis of Rosai-Dorfman Disease in the setting of prominent infradiaphragmatic lymphadenopathy, clinicians should maintain a high index of suspicion for the presence of occult non-Hodgkin's lymphoma especially if the clinical course is atypical for classic Rosai-Dorfman Disease
Exploring the role of competing demands and routines during the implementation of a self-management tool for type 2 diabetes: A theory-based qualitative interview study
Background
The implementation of new medical interventions into routine care involves healthcare professionals adopting new clinical behaviours and changing existing ones. Whilst theory-based approaches can help understand healthcare professionals’ behaviours, such approaches often focus on a single behaviour and conceptualise its performance in terms of an underlying reflective process. Such approaches fail to consider the impact of non-reflective influences (e.g. habit and automaticity) and how the myriad of competing demands for their time may influence uptake. The current study aimed to apply a dual process theoretical approach to account for reflective and automatic determinants of healthcare professional behaviour while integrating a multiple behaviour approach to understanding the implementation and use of a new self-management tool by healthcare professionals in the context of diabetes care.
Methods
Following Diabetes UK’s national release of the ‘Information Prescription’ (DUK IP; a self-management tool targeting the management of cholesterol, blood pressure and HbA1c) in January 2015, we conducted semi-structured interviews with 13 healthcare professionals (general practitioners and nurses) who had started to use the DUK IP during consultations to provide self-management advice to people with type 2 diabetes. A theory-based topic guide included pre-specified constructs from a previously developed logic model. We elicited healthcare professionals’ views on reflective processes (outcome expectations, self-efficacy, intention, action and coping planning), automatic processes (habit), and multiple behaviour processes (goal priority, goal conflict and goal facilitation). All interviews were audio recorded and transcribed verbatim and all transcripts were independently double coded and analysed using content analysis.
Results
The majority of healthcare professionals interviewed reported strong intentions to use the DUK IP and having formed a habit of using them after a minimum of one month continuous use. Pop-up cues in the electronic patient records were perceived to facilitate the use of the tool. Factors that conflicted with the use of the DUK IP included existing pathways of providing self-management advice.
Conclusion
Data suggests that constructs from dual process and multiple behaviour approaches are useful to provide supplemental understanding of the implementation of new self-management tools such as the DUK IP and may help to advance behavioural approaches to implementation science
Protein expression, survival and docetaxel benefit in node-positive breast cancer treated with adjuvant chemotherapy in the FNCLCC - PACS 01 randomized trial
International audienceABSTRACT: INTRODUCTION: The PACS01 trial has demonstrated that docetaxel addition to adjuvant anthracycline-based chemotherapy improves disease-free survival (DFS) and overall survival of node-positive early breast cancer (EBC). We searched for prognostic and predictive markers for docetaxel benefit. METHODS: Tumor samples from 1.099 recruited women were analyzed for the expression of 34 selected proteins using immunohistochemistry. The prognostic and predictive values of each marker and four molecular subtypes (luminal A, luminal B, HER2-overexpressing, and triple-negative) were tested. RESULTS: Progesterone receptor-negativity (HR=0.66; 95%CI 0.47-0.92, P=0.013), and Ki67-positivity (HR=1.53; 95%CI 1.12-2.08, P=0.007) were independent adverse prognostic factors. Out of the 34 proteins, only Ki67-positivity was associated with DFS improvement with docetaxel addition (adjusted HR=0.51, 95%CI 0.33-0.79 for Ki67-positive versus HR=1.10, 95%CI 0.75-1.61 for Ki67-negative tumors, P for interaction=0.012). Molecular subtyping predicted the docetaxel benefit, but without providing additional information to Ki67 status. The luminal A subtype did not benefit from docetaxel (HR=1.16, 95%CI 0.73-1.84); the reduction in the relapse risk was 53% (HR=0.47, 95%CI 0.22-1.01), 34% (HR=0.66, 95%CI 0.37-1.19), and 12% (HR=0.88, 95%CI 0.49-1.57) in the luminal B, HER2-overexpressing, and triple-negative subtypes, respectively. CONCLUSIONS: In patients with node-positive EBC receiving adjuvant anthracycline-based chemotherapy, the most powerful predictor of docetaxel benefit is Ki67-positivity
Effect of Levels of Acetate on the Mevalonate Pathway of Borrelia burgdorferi
Borrelia burgdorferi, the agent of Lyme disease, is a spirochetal pathogen with limited metabolic capabilities that survives under highly disparate host-specific conditions. However, the borrelial genome encodes several proteins of the mevalonate pathway (MP) that utilizes acetyl-CoA as a substrate leading to intermediate metabolites critical for biogenesis of peptidoglycan and post-translational modifications of proteins. In this study, we analyzed the MP and contributions of acetate in modulation of adaptive responses in B. burgdorferi. Reverse-transcription PCR revealed that components of the MP are transcribed as individual open reading frames. Immunoblot analysis using monospecific sera confirmed synthesis of members of the MP in B. burgdorferi. The rate-limiting step of the MP is mediated by HMG-CoA reductase (HMGR) via conversion of HMG-CoA to mevalonate. Recombinant borrelial HMGR exhibited a Km value of 132 µM with a Vmax of 1.94 µmol NADPH oxidized minute−1 (mg protein)−1 and was inhibited by statins. Total protein lysates from two different infectious, clonal isolates of B. burgdorferi grown under conditions that mimicked fed-ticks (pH 6.8/37°C) exhibited increased levels of HMGR while other members of the MP were elevated under unfed-tick (pH 7.6/23°C) conditions. Increased extra-cellular acetate gave rise to elevated levels of MP proteins along with RpoS, CsrABb and their respective regulons responsible for mediating vertebrate host-specific adaptation. Both lactone and acid forms of two different statins inhibited growth of B. burgdorferi strain B31, while overexpression of HMGR was able to partially overcome that inhibition. In summary, these studies on MP and contributions of acetate to host-specific adaptation have helped identify potential metabolic targets that can be manipulated to reduce the incidence of Lyme disease
ITALIAN CANCER FIGURES - REPORT 2015: The burden of rare cancers in Italy = I TUMORI IN ITALIA - RAPPORTO 2015: I tumori rari in Italia
OBJECTIVES:
This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities.
MATERIALS AND METHODS:
Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet "Information Network on Rare Cancers" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data.
RESULTS:
In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity.
COMMENTS:
One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
Impact of discharge medication counseling in the cardiology unit of a tertiary hospital in Brazil: A randomized controlled trial
© 2018 CLINICS. OBJECTIVES: This study aimed to evaluate the impact of pharmacist-provided discharge counseling on mortality rate, hospital readmissions, emergency department visits, and medication adherence at 30 days post discharge. METHODS: This randomized controlled trial was approved by the local ethics committee and included patients aged 18 years or older admitted to the cardiology ward of a Brazilian tertiary hospital. The intervention group received a pharmacist-led medication counseling session at discharge and a telephone follow-up three and 15 days after discharge. The outcomes included the number of deaths, hospital readmissions, emergency department visits, and medication adherence. All outcomes were evaluated during a pharmacist-led ambulatory consultation performed 30 days after discharge. RESULTS: Of 133 patients, 104 were included in the analysis (51 and 53 in the intervention and control groups, respectively). The intervention group had a lower overall readmission rate, number of emergency department visits, and mortality rate, but the differences were not statistically significant (p>0.05). However, the intervention group had a significantly lower readmission rate related to heart disease (0% vs. 11.3%, p=0.027), despite the small sample size. Furthermore, medication counseling contributed significantly to improved medication adherence according to three different tools (p<0.05). CONCLUSIONS: Pharmacist-provided discharge medication counseling resulted in better medication adherence scores and a lower incidence of cardiovascular-associated hospital readmissions, thus representing a useful service for cardiology patients
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