In France, more than 10 million women at "average" risk of breast cancer (BC), are included in the organized BC screening. Existing predictive models of BC risk are not adapted to the French ...population. Thus, we set up a new score in the French Hérault region and looked for subgroups at a graded level of risk in women at "average" risk. We recruited a retrospective cohort of women, aged 50 to 60, who underwent the organized BC screening, and included 2241 non-cancer women and 527 who developed a BC during a 12-year follow-up period (2006-2018). The risk factors identified were high breast density (ACR BI-RADS grading)(B vs A: HR = 1.41, 95%CI 1.05; 1.9, p = 0.023; C vs A: HR = 1.65 1.2; 2.27, p = 0.02 ; D vs A: HR = 2.11 1.25;3.58, p = 0.006), a history of maternal breast cancer (HR = 1.61 1.24; 2.09, p < 0.001), and socioeconomic difficulties (HR 1.23 1.09; 1.55, p = 0.003). While early menopause (HR = 0.36 0.13; 0.99, p = 0.003) and an age at menarche after 12 years (HR = 0.77 0.63; 0.95, p = 0.047) were protective factors. We identified 3 groups at risk: lower, average, and higher, respectively. A low threshold was characterized at 1.9% of 12-year risk and a high threshold at 4.5% 12-year risk. Mean 12-year risks in the 3 groups of risk were 1.37%, 2.68%, and 5.84%, respectively. Thus, 12% of women presented a level of risk different from the average risk group, corresponding to 600,000 women involved in the French organized BC screening, enabling to propose a new strategy to personalize the national BC screening. On one hand, for women at lower risk, we proposed to reduce the frequency of mammograms and on the other hand, for women at higher risk, we suggested intensifying surveillance.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Cachexia and sarcopenia were analyzed in NSCLC patients receiving immune checkpoint inhibitors.•This syndrome reduced the probability of achieving a disease control.•Cachexia was associated with a ...shorter overall survival.•In addition, patients with an evolving sarcopenia had shorter PFS and overall survival.
The metabolic changes associated with cachexia – sarcopenia syndrome might down-regulate antitumor immunity. We hypothesized that this syndrome reduces efficiency of immune checkpoint inhibitors (ICPI) in non-small cell lung cancer (NSCLC).
The records of 142 consecutive NSCLC patients receiving first- or second-line anti-Programmed cell death protein 1) ICPI were reviewed. Response evaluation according to Response Evaluation Criteria in Solid Tumors 1.1 was performed at the eighth week of immunotherapy. Pretreatment cachexia was defined as a body-weight loss of 5% or more in the previous 6 months. Sarcopenia was estimated with the third lumbar skeletal muscle mass index (mSMI) and was evaluated before immunotherapy and at the eighth week. A decrease by 5% or more of the mSMI was considered as an evolving sarcopenia. The endpoints were disease control rate (DCR), progression-free (PFS) and overall survival (OS).Logistic regression model and Cox model took into account others covariables known to influence ICPI efficiency, particularly Programmed Death –Ligand 1 tumor cell score, Eastern Cooperative Oncology Group performance status and common somatic mutational status.
In multivariate analysis, cachexia – sarcopenia syndrome reduced the probability of achieving a disease control and were associated with a shorter survival. Patients without cachexia had a better probability to achieve disease control in comparison with those who did not experience cachexia (59.9 % and 41.1 %, respectively; odds ratio 95 % (confidence interval 95 %CI): 2.60 (1.03–6.58)). Patients with cachexia had a shorter OS when compared with those without cachexia (hazard ratios HR (95 %CI): 6.26 (2.23–17.57)). Patients with an evolving sarcopenia had a shorter PFS and OS, with HR (95 %CI): 2.45 (1.09–5.53) and 3.87 (1.60–9.34) respectively.
Cachexia – sarcopenia syndrome negatively influences patients’ outcome during anti-PD-1 ICPI therapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Acute‐on‐chronic liver failure (ACLF) is associated with a significant short‐term mortality rate (23%‐74%), depending on the number of organ failures. Some patients present with ACLF at ...the time of liver transplantation (LT). The aim of this study was to assess whether ACLF was also a prognostic factor after LT and, if applicable, to construct a score that could predict 90‐day mortality.
Methods
Three hundred and fifty cirrhotic patients, who underwent LT between January 2008 and December 2013, were enrolled. We used ACLF grades according to EASL‐CLIF consortium criteria to categorize the cirrhotic patients. A propensity score was applied with an Inverse Probability Treatment Weighting in a Cox model. A predictive score of early mortality after LT was generated.
Results
One hundred and forty patients (40%) met the criteria for ACLF. The overall mortality rate at 90 days post‐transplant was 10.6% (37/350 patients). ACLF at the time of LT (HR: 5.78 3.42‐9.77, P<.001) was an independent predictor of 90‐day mortality. Infection occurring during the month before LT, high recipient age and male recipient, the reason for LT and a female donor were also independent risk factors for early mortality. Using these factors, we have proposed a model to predict 90‐day mortality after LT.
Conclusions
LT is feasible in cirrhotic patients with ACLF. However, we have shown that ACLF is a significant and independent predictor of 90‐day mortality. We propose a score that can identify candidate cirrhotic patients in whom LT might be associated with futile LT.
See Editorial on Page 651
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Double-adjustment can be used to remove confounding if imbalance exists after propensity score (PS) matching. However, it is not always possible to include all covariates in adjustment. We aimed to ...find the optimal imbalance threshold for entering covariates into regression.
We conducted a series of Monte Carlo simulations on virtual populations of 5,000 subjects. We performed PS 1:1 nearest-neighbor matching on each sample. We calculated standardized mean differences across groups to detect any remaining imbalance in the matched samples. We examined 25 thresholds (from 0.01 to 0.25, stepwise 0.01) for considering residual imbalance. The treatment effect was estimated using logistic regression that contained only those covariates considered to be unbalanced by these thresholds.
We showed that regression adjustment could dramatically remove residual confounding bias when it included all of the covariates with a standardized difference greater than 0.10. The additional benefit was negligible when we also adjusted for covariates with less imbalance. We found that the mean squared error of the estimates was minimized under the same conditions.
If covariate balance is not achieved, we recommend reiterating PS modeling until standardized differences below 0.10 are achieved on most covariates. In case of remaining imbalance, a double adjustment might be worth considering.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This prospective multicenter study evaluated the prognostic value of circulating tumor cells (CTCs) in relapsing nonoperable or metastatic head and neck squamous cell carcinoma (rHNSCC) treated by ...chemotherapy and cetuximab.
In 65 patients suitable for analyses, peripheral blood was taken at day 0 (D
) D
, and D
of treatment for CTC detection by CellSearch
, EPISPOT, and flow cytometry (FCM). Progression-free survival (PFS) was assessed with the Kaplan-Meier method and compared with the log-rank test (
< 0.05).
At D
, CTCs were detected with EPISPOT, CellSearch, and FCM in 69% (45/65), 21% (12/58), and 11% (7/61) of patients, respectively. In the patients tested with all 3 methods, EPISPOT identified 92% (36/39), 92% (35/38), and 90% (25/28) of all positive samples at D
, D
, and D
, respectively. Median PFS time was significantly lower in (
) patients with increasing or stable CTC counts (36/54) from D
to D
with EPISPOT
(3.9 vs 6.2 months; 95% CI, 5.0-6.9;
= 0.0103) and (
) patients with ≥1 CTC detected with EPISPOT or CellSearch
(37/51) (
= 0.0311), EPISPOT or FCM (38/54) (
= 0.0480), and CellSearch or FCM (11/51) (
= 0.0005) at D
.
CTCs can be detected before and during chemotherapy in patients with rHNSCC. D
-D
CTC kinetics evaluated with EPISPOT
are associated with the response to treatment. This study indicates that CTCs can be used as a real-time liquid biopsy to monitor the early response to chemotherapy in rHNSCC.
NCT02119559.
Summary
Purpose: To determine the prevalence of epilepsy in a defined adult population and identify the frequency and principal features of pharmacoresistant epilepsy.
Methods: From a population over ...15 years of age residing in a medium‐sized French city, all patients with epilepsy on June 30, 1995 were identified from multiple sources. Pharmacoresistance was defined as failure to control epilepsy by at least two first‐line antiepileptic drugs, with a seizure frequency of at least one per month for 18 months. Collected data were examined by experts in epileptology, and responding patients were reexamined using a standardized diagnostic questionnaire. ILAE definitions and classifications were used.
Results: The age‐adjusted prevalence of active epilepsy was 5.4 per 1,000 (95% CI: 4.7–6.0) and was higher for males (7.8) than for females (5.2). For epilepsy in remission under treatment, this rate was 0.7 per 1,000 (95% CI: 0.5–0.95). Age‐specific prevalence was highest in age groups 25–49 years and declined in the oldest age groups. Localization‐related seizures represented 61.1% of cases and generalized seizures 30.9%. The proportion of noncontrolled epilepsy (seizure‐frequency at least one per month for 18 months) was 15.6%, corresponding to a prevalence of 0.94 per 1,000. In this group, the mean age at onset was lower (p = 0.0007) and localization‐related epilepsy more frequent (p = 0.01).
Conclusion: The findings support previous epidemiological estimates of the prevalence of epilepsy in developed countries. For approximately one patient in eight, epilepsy was not adequately controlled.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The incidence and number of circulating tumor cells (CTCs) in the peripheral blood of colorectal cancer patients are lower than in other cancer types, which may point to a particular biology of ...colorectal cancer affecting CTC detection.
We detected CTCs in the peripheral and mesenteric blood of colorectal cancer patients by use of 2 independent technologies on the basis of different biological properties of colon cancer cells. Seventy-five patients diagnosed with localized (M0, n = 60) and metastatic (M1, n = 15) colorectal cancer were included. Peripheral and mesenteric blood samples were collected before tumor resection. We performed CTC enumeration with an EpCAM-independent enrichment method followed by the Epispot assay that detected only viable CK19-releasing CTCs. In parallel, we used the FDA-cleared EpCAM-dependent CellSearch® as the reference method.
The enumeration of CK19-releasing cells by the CK19-Epispot assay revealed viable CTCs in 27 of 41 (65.9%) and 41 of 74 (55.4%) (P = 0.04) patients in mesenteric and peripheral blood, respectively, whereas CellSearch detected CTCs in 19 of 34 (55.9%) and 20 of 69 (29.0%) (P = 0.0046) patients. In mesenteric blood, medians of 4 (range 0-247) and 2.7 CTCs (range 0-286) were found with Epispot and CellSearch (P = 0.2), respectively, whereas in peripheral blood, Epispot and CellSearch detected a median of 1.2 (range 0-92) and 0 CTCs (range 0-147) (P = 0.002).
A considerable portion of viable CTCs detectable by the Epispot assay are trapped in the liver as the first filter organ in CRC patients.
The public health implications of asthma BOUSQUET, Jean; BOUSQUET, Philippe J; GODARD, Philippe ...
Bulletin of the World Health Organization,
07/2005, Volume:
83, Issue:
7
Journal Article
Peer reviewed
Open access
Asthma is a very common chronic disease that occurs in all age groups and is the focus of various clinical and public health interventions. Both morbidity and mortality from asthma are significant. ...The number of disability-adjusted life years (DALYs) lost due to asthma worldwide is similar to that for diabetes, liver cirrhosis and schizophrenia. Asthma management plans have, however, reduced mortality and severity in countries where they have been applied. Several barriers reduce the availability, affordability, dissemination and efficacy of optimal asthma management plans in both developed and developing countries. The workplace environment contributes significantly to the general burden of asthma. Patients with occupational asthma have higher rates of hospitalization and mortality than healthy workers. The surveillance of asthma as part of a global WHO programme is essential. The economic cost of asthma is considerable both in terms of direct medical costs (such as hospital admissions and the cost of pharmaceuticals) and indirect medical costs (such as time lost from work and premature death). Direct costs are significant in most countries. In order to reduce costs and improve quality of care, employers and health plans are exploring more precisely targeted ways of controlling rapidly rising health costs. Poor control of asthma symptoms is a major issue that can result in adverse clinical and economic outcomes. A model of asthma costs is needed to aid attempts to reduce them while permitting optimal management of the disease. This paper presents a discussion of the burden of asthma and its socioeconomic implications and proposes a model to predict the costs incurred by the disease.
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CEKLJ, DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Comprehensive geriatric assessment (CGA) is recommended to assess the vulnerability of elderly patients, but its integration in cancer treatment decision making has never been prospectively ...evaluated. Here, in elderly patients with advanced non-small-cell lung cancer (NSCLC), we compared a standard strategy of chemotherapy allocation on the basis of performance status (PS) and age with an experimental strategy on the basis of CGA.
In a multicenter, open-label, phase III trial, elderly patients ≥ 70 years old with a PS of 0 to 2 and stage IV NSCLC were randomly assigned between chemotherapy allocation on the basis of PS and age (standard arm: carboplatin-based doublet if PS ≤ 1 and age ≤ 75 years; docetaxel if PS = 2 or age > 75 years) and treatment allocation on the basis of CGA (CGA arm: carboplatin-based doublet for fit patients, docetaxel for vulnerable patients, and best supportive care for frail patients). The primary end point was treatment failure free survival (TFFS). Secondary end points were overall survival (OS), progression-free survival, tolerability, and quality of life.
Four hundred ninety-four patients were randomly assigned (standard arm, n = 251; CGA arm, n = 243). Median age was 77 years. In the standard and CGA arms, 35.1% and 45.7% of patients received a carboplatin-based doublet, 64.9% and 31.3% received docetaxel, and 0% and 23.0% received best supportive care, respectively. In the standard and CGA arms, median TFFS times were 3.2 and 3.1 months, respectively (hazard ratio, 0.91; 95% CI, 0.76 to 1.1), and median OS times were 6.4 and 6.1 months, respectively (hazard ratio, 0.92; 95% CI, 0.79 to 1.1). Patients in the CGA arm, compared with standard arm patients, experienced significantly less all grade toxicity (85.6% v 93.4%, respectively P = .015) and fewer treatment failures as a result of toxicity (4.8% v 11.8%, respectively; P = .007).
In elderly patients with advanced NSCLC, treatment allocation on the basis of CGA failed to improve the TFFS or OS but slightly reduced treatment toxicity.
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