Systemic treatments for women with breast cancer: outcome with relation to screening for the disease

Early detection and proper care of breast cancer are currently the best available approaches to the treatment of patients with the disease. In countries with a breast cancer screening programme, there has been a demonstrated reduction in breast cancer-related mortality. Such reduction has also been observed in Switzerland, a country in which no national programme of screening is available. Although there is no doubt that early diagnosis might have had a major role in reducing breast cancer mortality the magnitude of this effect is unknown. Research with tailored approaches on alternative imaging for early detection of breast cancer in high-risk women and on treatments offered according to proper criteria of responsiveness to therapies is warrante

Usage personnel de pratiques relevant des médecines douces ou alternatives parmi les médecins suisses

L'importance de l'utilisation pour des besoins personnels de pratiques relevant des médecines douces ou alternatives parmi les médecins est très mal connue. Elle pourrait avoir plusieurs implications notamment par rapport à l'effort actuel de promotion de pratiques médicales fondées sur des preuves d'efficacité (Evidence-based medicine, EBM). [Auteurs]]]> fre oai:serval.unil.ch:BIB_F32E44E67757 2022-05-07T01:30:01Z openaire documents urnserval <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_F32E44E67757 PAX5 activates the transcription of the human telomerase reverse transcriptase gene in B cells. info:doi:10.1002/path.2620 info:eu-repo/semantics/altIdentifier/doi/10.1002/path.2620 info:eu-repo/semantics/altIdentifier/pmid/19806612 Bougel, Stephanie Renaud, Stephanie Braunschweig, Richard Loukinov, Dmitri Morse Herbert C. III, Bosman Fred, T. Lobanenkov, Victor Benhattar, Jean info:eu-repo/semantics/article article 2010 Journal of Pathology, vol. 220, no. 1, pp. 87-96 info:eu-repo/semantics/altIdentifier/pissn/1096-9896[electronic] <![CDATA[Telomerase is an RNA-dependent DNA polymerase that synthesizes telomeric DNA. Its activity is not detectable in most somatic cells but it is reactivated during tumorigenesis. In most cancers, the combination of hTERT hypermethylation and hypomethylation of a short promoter region is permissive for low-level hTERT transcription. Activated and malignant lymphocytes express high telomerase activity, through a mechanism that seems methylation-independent. The aim of this study was to determine which mechanism is involved in the enhanced expression of hTERT in lymphoid cells. Our data confirm that in B cells, some T cell lymphomas and non-neoplastic lymph nodes, the hTERT promoter is unmethylated. Binding sites for the B cell-specific transcription factor PAX5 were identified downstream of the ATG translational start site through EMSA and ChIP experiments. ChIP assays indicated that the transcriptional activation of hTERT by PAX5 does not involve repression of CTCF binding. In a B cell lymphoma cell line, siRNA-induced knockdown of PAX5 expression repressed hTERT transcription. Moreover, ectopic expression of PAX5 in a telomerase-negative normal fibroblast cell line was found to be sufficient to activate hTERT expression. These data show that activation of hTERT in telomerase-positive B cells is due to a methylation-independent mechanism in which PAX5 plays an important role

Observational case-control study of non-invasive ventilation in patients with ARDS

Background. The application of non-invasive pressure support ventilation (NIPSV) in patients with acute lung injury or ARDS remains controversial despite recent promising results. Data in rather homogeneous ARDS groups is lacking. Objective. To compare the outcome of NIPSV-treated patients satisfying the diagnostic criteria for primary (pulmonary) ARDS (ARDSp) and presenting without distant organ failures at admission, with those of a matched control group treated in the same ICU with endotracheal mechanical ventilation (ETMV). Methods. We applied NIPSV in 12 immunocompetent and collaborative patients who met the above cited criteria. NIPSV failure rate, short-term oxygenation, length of stay, mortality rate and complications were analyzed and compared with a control group of 12 intubated ARDSp-patients matched for age, SAPS II, PaO2/FiO2 and pH at admission. Results. NIPSV failed in 4 patients developing distant organ failures. Compared to the ETMV control group, NIPSV success patients had reduced cumulative time on ventilation (p = 0.001) and length of ICU stay (p = 0.004). After the first 60’ of ventilation, oxygenation improved more in the NIPSV than in the ETMV group (146 ± 52 mmHg vs 109 ± 34 mmHg; p = 0.05). The overall ICU mortality rate did not differ significantly between the groups but tended to be higher in the NIPSV group. Conclusions. In ARDSp patients without distant organ failures at admission and during the disease course, NIPSV might be a suitable alternative to invasive ventilation; however, the real effects on outcome of NIPSV applied to stable homogeneous subgroups of ARDS patients merit further investigations in randomised studies

Systemic treatments for women with breast cancer: outcome with relation to screening for the disease

Early detection and proper care of breast cancer are currently the best available approaches to the treatment of patients with the disease. In countries with a breast cancer screening programme, there has been a demonstrated reduction in breast cancer-related mortality. Such reduction has also been observed in Switzerland, a country in which no national programme of screening is available. Although there is no doubt that early diagnosis might have had a major role in reducing breast cancer mortality the magnitude of this effect is unknown. Research with tailored approaches on alternative imaging for early detection of breast cancer in high-risk women and on treatments offered according to proper criteria of responsiveness to therapies is warranted

Bosentan therapy for chronic thromboembolic pulmonary hypertension. A national open label study assessing the effect of Bosentan on haemodynamics, exercise capacity, quality of life, safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (BOCTEPH-Study).

we performed an open-label national study to evaluate the effects of Bosentan on haemodynamics, exercise capacity, quality of life, safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (CTEPH). fifteen patients with CTEPH not eligible or waiting for surgery were enrolled. The primary endpoint was the change in pulmonary vascular resistance (PVR). Secondary endpoints included quality of life (measured by the Minnesota living with heart failure questionnaire, MLHF), 6 minute walk distance (6MWD), World Health Organization (WHO) functional class, Borg dyspnoea scale, plasma endothelin, serum values of disease severity such as uric acid, N-terminal-pro brain natriuretic peptide (NTproBNP), C-reactive protein measured by a highly sensitive method (CRPs) and other serum and haemodynamic parameters. after six months of treatment with bosentan, the PVR decreased from 852 (319) to 657(249) dyn*s*m-5 (p = 0.02). Quality of life considerably improved from a mean total score of 48(14) to 35(17) (p = 0.003) with improvements in the physical (from 25(5) to 17(7)) and emotional (from 11(6) to 6(5)) subscores (p = 0.005 and 0.011), respectively. The 6MWD improved from 389(78) to 443(79) meters (p = 0.005). 4 patients (27%) improved and 11 patients (73%) maintained their WHO class with no deterioration during the six months of bosentan treatment (p = 0.02). Uric acid serum levels declined from 525(145) to 453(151) micromol/l (p = 0.006), NTproBNP and CRPs declined insignificantly. Endothelin serum levels increased from 4.3(1.5) to 5.9(2.2) pg/ml (p = 0.025). Patients tolerated the treatment well, and there were no severe adverse events or deaths. this open-label study suggests a beneficial effect of bosentan therapy not only on pulmonary haemodynamics, but also on quality of life and exercise capacity for patients with severe CTEPH

Loss of FHL1 induces an age-dependent skeletal muscle myopathy associated with myofibrillar and intermyofibrillar disorganization in mice

Recent human genetic studies have provided evidences that sporadic or inherited missense mutations in four-and-a-half LIM domain protein 1 (FHL1), resulting in alterations in FHL1 protein expression, are associated with rare congenital myopathies, including reducing body myopathy and Emery–Dreifuss muscular dystrophy. However, it remains to be clarified whether mutations in FHL1 cause skeletal muscle remodeling owing to gain- or loss of FHL1 function. In this study, we used FHL1-null mice lacking global FHL1 expression to evaluate loss-of-function effects on skeletal muscle homeostasis. Histological and functional analyses of soleus, tibialis anterior and sternohyoideus muscles demonstrated that FHL1-null mice develop an age-dependent myopathy associated with myofibrillar and intermyofibrillar (mitochondrial and sarcoplasmic reticulum) disorganization, impaired muscle oxidative capacity and increased autophagic activity. A longitudinal study established decreased survival rates in FHL1-null mice, associated with age-dependent impairment of muscle contractile function and a significantly lower exercise capacity. Analysis of primary myoblasts isolated from FHL1-null muscles demonstrated early muscle fiber differentiation and maturation defects, which could be rescued by re-expression of the FHL1A isoform, highlighting that FHL1A is necessary for proper muscle fiber differentiation and maturation in vitro. Overall, our data show that loss of FHL1 function leads to myopathy in vivo and suggest that loss of function of FHL1 may be one of the mechanisms underlying muscle dystrophy in patients with FHL1 mutations

Overdiagnosis and overtreatment of breast cancer: Is overdiagnosis an issue for radiologists?

Overdiagnosis is diagnosis of cancers that would not present within the life of the patient and is one of the downsides of screening. This applies to low-grade ductal carcinoma in situ and some small grade 1 invasive cancers. Radiologists are responsible for cancer diagnosis, but at the time of diagnosis they cannot determine whether a particular low-grade diagnosis is one to which the definition of overdiagnosis applies. Overdiagnosis is likely to be driven by technological developments, including digital mammography, computer-aided detection and improved biopsy techniques. It is also driven by the patient's fear that cancer will be missed and the doctor's fear of litigation. It is therefore an issue of importance for radiologists, presenting them with difficult fine-tuned decisions in every assessment clinic that are ultimately counted later by those who evaluate their screening

Exploring the impact of providing evidence-based medicine training to service users

© 2015 Gibson et al. Background Within the UK, health services research in the 1990s was marked by growing interest in evidence-based medicine (EBM) and in the potential of patient and public involvement (PPI) in research. However, there has been relatively little discussion of how these two developments might relate to each other, despite their common concern to improve the quality and transparency of clinical decision making. Indeed, some in the user involvement movement have expressed doubts about the implications of EBM for PPI. The purpose of this paper is to examine the potential for EBM and PPI to complement one another. Methods We used a case study design. Fifteen EBM workshops, involving PPI members, were conducted between June 2010 and December 2014. All 13 lay participants, who attended the first five workshops, were asked to fill in a standard feedback proforma designed by a member of the NIHR Collaboration for Leadership in Applied Health Research and Care for the South West Peninsula (PenCLAHRC) Public Involvement Group (PenPIG). Ten responses were received, and these were analysed thematically. Results Four themes emerged from the thematic analysis: research knowledge, research skills, shared clinical decision making and learning environment. Participation in the workshops appears to have increased the ability and confidence of members of the public to actively participate as both producers and consumers of research evidence. Conclusions There is an untapped potential for EBM and PPI to complement one another in their shared desire to improve the quality and transparency of clinical decision making

Incentive Compatible Reimbursement Schemes for Physicians

We consider physicians with fixed capacity levels. If a physician’s capacity exceeds demand, she may have an incentive to overtreat, i.e., she may provide unnecessary treatments to use up idle capacity. By contrast, with excess demand she may undertreat, i.e., she may not provide necessary treatments since other activities are financially more attractive. We first show that simple fee-for-service reimbursement schemes do not provide proper incentives. If insurers use, however, fee-for-service schemes with quantity restrictions, they solve the fraudulent physician problem

Mammographic screening for young women with a family history of breast cancer: knowledge and views of those at risk

Although the effectiveness of mammography for women under the age of 50 years with a family history of breast cancer (FHBC) has not yet been proven, annual screening is being offered to these women to manage breast cancer risk. This study investigates women's awareness and interpretation of their familial risk and knowledge and views about mammographic screening. A total of 2231 women from 21 familial/breast/genetics centres who were assessed as moderate risk (17–30% lifetime risk) or high risk (>30% lifetime risk) completed a questionnaire before their mammographic screening appointment. Most women (70%) believed they were likely, very likely or definitely going to develop breast cancer in their lifetime. Almost all women (97%) understood that the purpose of mammographic screening was to allow the early detection of breast cancer. However, 20% believed that a normal mammogram result meant there was definitely no breast cancer present, and only 4% understood that screening has not been proven to save lives in women under the age of 50 years. Women held positive views on mammography but did not appear to be well informed about the potential disadvantages. These findings suggest that further attention should be paid to improving information provision to women with an FHBC being offered routine screening