Functional forms of socio-territorial inequities in breast cancer screening – A French cross-sectional study using hierarchical generalised additive models

To reduce the breast cancer burden, the French National Organised Breast Cancer Screening Programme (FNOBCSP) was implemented in 2004. The recommended participation rate has never been achieved and socio-territorial inequities in participation have been reported on several occasions. We investigated the functional forms and consistency of the relationships between neighbourhood deprivation, travel time to the nearest accredited radiology centre and screening uptake. We used two-level hierarchical generalised additive models in 8 types of territories classified by socio-demographic and economic factors. The first level was 368,201 women aged 50–72 invited to the 2013–2014 screening campaign in metropolitan France. They were nested in 41 départements, the level of organisation of the FNOBCSP. The effect of travel time showed two main patterns: it was either linear (with participation decreasing as travel time increased) or participation first increased with increasing travel time to a peak around 5–15 min and decreased afterward. In nearly all types and départements, the probability of participation decreased linearly with increasing deprivation. Territorial inequities in participation were more context-dependent and complex than social inequities. Inequities in participation represent a loss of opportunity for individuals who already have the worst cancer outcomes. Evidence-based public health policies are needed to increase the effectiveness and equity of breast cancer screening

Evidence for two-electron processes in the mutual neutralization of O- with O+ and N+ at Subthermal Collision Energies

We have measured total absolute cross sections for the Mutual Neutralization (MN) of O- with O+/N+. A fine resolution (of about 50 meV) in the kinetic energy spectra of the product neutral atoms allows unique identification of the atomic states participating in the mutual neutralization process. Cross sections and branching ratios have also been calculated down to 1 meV center-of-mass collision energy for these two systems with a multi-channel Landau-Zener model and an asymptotic method for the ionic-covalent coupling matrix elements. The importance of two-electron processes in one-electron transfer is demonstrated by the dominant contribution of a core-excited configuration of the nitrogen atom in N+ + O- collisions. This effect is partially accounted for by introducing configuration mixing in the evaluation of coupling matrix elements.Comment: 5 pages, 4 figure

TP53 mutations, amplification of P63 and expression of cell cycle proteins in squamous cell carcinoma of the oesophagus from a low incidence area in Western Europe

In Europe, high incidence rates of oesophageal squamous cell carcinoma (SCCE) are observed in western France (Normandy and Brittany) and in north-eastern Italy. Analysis of TP53 mutations in tumours from these regions has shown a high prevalence of mutations at A:T basepairs that may result from DNA damage caused by specific mutagens. However, the spectrum of TP53 mutations in regions of low incidence is unknown. We report here TP53 mutation analysis in 33 SCCE collected in Lyon, an area of low incidence. These tumours were also examined for MDM2 and P63 amplification, and for expression of p16INK4a/CDKN2a, cyclin E, p27Kipland Cox2. TP53 mutations were detected in 36% of the cases (12/33). In contrast with regions of high incidence, the mutation spectrum did not show a high prevalence of mutations at A:T base pairs. P63 was amplified in 5/32 cases tested (15.5%). No amplification of MDM2 was found. Expression studies revealed frequent loss of p16INK4a/CDKN2a(46%) and p27Kipl(25%) expression, and frequent overexpression of Cyclin E (70%) and Cox2 (42%). Overall, these results indicate that in Europe, SCCE from areas of high and low incidence present a similar pattern of molecular alterations but differ by the type of TP53 mutations. © 2001 Cancer Research Campaign http://www.bjcancer.co

Socioeconomic and geographic determinants of survival of patients with digestive cancer in France

Using a multilevel Cox model, the association between socioeconomic and geographical aggregate variables and survival was investigated in 81 268 patients with digestive tract cancer diagnosed in the years 1980–1997 and registered in 12 registries in the French Network of Cancer Registries. This association differed according to cancer site: it was clear for colon (relative risk (RR)=1.10 (1.04–1.16), 1.10 (1.04–1.16) and 1.14 (1.05–1.23), respectively, for distances to nearest reference cancer care centre between 10 and 30, 30 and 50 and more than 90 km, in comparison with distance of less than 10 km; P-trend=0.003) and rectal cancer (RR=1.09 (1.03–1.15), RR=1.08 (1.02–1.14) and RR=1.12 (1.05–1.19), respectively, for distances between 10 and 30 km, 30 and 50 km and 50 and 70 km, P-trend=0.024) (n=28 010 and n=18 080, respectively) but was not significant for gall bladder and biliary tract cancer (n=2893) or small intestine cancer (n=1038). Even though the influence of socioeconomic status on prognosis is modest compared to clinical prognostic factors such as histology or stage at diagnosis, socioeconomic deprivation and distance to nearest cancer centre need to be considered as potential survival predictors in digestive tract cancer

In Trauma Patients, the Occurrence of Early-Onset Nosocomial Infections is Associated With Increased Plasma Concentrations of Chromogranin A:

In previously healthy persons suffering from acute illnesses, nosocomial infections (NIs) are frequent. Their prevalence suggests the existence of as yet unknown conditions that may promote care-related infection. This study assessed whether the measurement of plasma chromogranin A, a stress-related protein involved in innate defense, is related to NI risk, and whether any chromogranin A-derived fragment included in vasostatin-I displays immunosuppressive activities related to AP-1 or NF-kappa B downregulation. At the clinical level, trauma patients and healthy controls were recruited to be eligible. Clinical histories were recorded, and standard biological tests (including plasma chromogranin A) were performed. For 9 randomly chosen patients and 16 controls, the time-dependent concentrations of chromogranin A (CGA) were assessed twice a day over 66 h. The data show that trauma patients present a higher value of CGA concentration during 66 h in comparison with healthy controls. In addition, patients maintaining this significant increase in CGA readily develop NIs. We therefore studied the effects of chromogranin A-derived peptides on monocytes, focusing on transcription factors that play a central role in inflammation. In vitro assay demonstrated that a chromogranin A-derived fragment (CGA47-70) displays a significant inhibition of NF-kappa B and AP-1 transcriptional activities in these cells. In conclusion, the occurrence of NI in trauma patients is associated with significantly increased plasma CGA concentrations. Downregulation of the two transcription factors by CGA47-70 might induce early acquired immune defect after a serious medical stress

Impact of deprivation and rural residence on treatment of colorectal and lung cancer

For common cancers, survival is poorer for deprived and outlying, rural patients. This study investigated whether there were differences in treatment of colorectal and lung cancer in these groups. Case notes of 1314 patients in north and northeast Scotland who were diagnosed with lung or colorectal cancer in 1995 or 1996 were reviewed. On univariate analysis, the proportions of patients receiving surgery, chemotherapy and radiotherapy appeared similar in all socio-economic and rural categories. Adjusting for disease stage, age and other factors, there was less chemotherapy among deprived patients with lung cancer (odds ratio 0.39; 95% confidence intervals 0.16 to 0.96) and less radiotherapy among outlying patients with colorectal cancer (0.39; 0.19 to 0.82). The time between first referral and treatment also appeared similar in all socio-economic and rural groups. Adjusting for disease stage and other variables, times to lung cancer treatment remained similar, but colorectal cancer treatment was quicker for outlying patients (adjusted hazard ratio 1.30; 95% confidence intervals 1.03 to 1.64). These findings suggest that socio-economic status and rurality may have a minor impact on modalities of treatment for colorectal and lung cancer, but do not lead to delays between referral and treatment

Rural factors and survival from cancer: analysis of Scottish cancer registrations

In this survival study 63 976 patients diagnosed with one of six common cancers in Scotland were followed up. Increasing distance from a cancer centre was associated with less chance of diagnosis before death for stomach, breast and colorectal cancers and poorer survival after diagnosis for prostate and lung cancers. © 2000 Cancer Research Campaig

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015