Incidence and risk factors of prolonged grief in relatives of patients with terminal cancer in French palliative care units: The Fami-Life multicenter cohort study.

OBJECTIVES: Psychological consequences of grief among relatives are insufficiently known. We reported incidence of prolonged grief among relatives of deceased patients with cancer. METHODS: Prospective cohort study of 611 relatives of 531 patients with cancer hospitalized for more than 72 hours and who died in 26 palliative care units was conducted. The primary outcome was prolonged grief in relatives 6 months after patient death, measured with the Inventory Complicated Grief (ICG > 25, range 0-76, a higher score indicates more severe symptoms) score. Secondary outcomes in relatives 6 months after patient death were anxiety and depression symptoms based on Hospital Anxiety and Depression Scale (HADS) score (range 0 [best]-42 [worst]), higher scores indicate more severe symptoms, minimally important difference 2.5. Post-traumatic stress disorder symptoms were defined by an Impact Event Scale-Revised score >22 (range 0-88, a higher score indicates more severe symptoms). RESULTS: Among 611 included relatives, 608 (99.5%) completed the trial. At 6 months, significant ICG scores were reported by 32.7% relatives (199/608, 95% CI, 29.0-36.4). The median (interquartile range ICG score) was 20.0 (11.5-29.0). The incidence of HADS symptoms was 87.5% (95% CI, 84.8-90.2%) at Days 3-5 and 68.7% (95% CI, 65.0-72.4) 6 months after patient's death, with a median (interquartile range) difference of -4 (-10 to 0) between these 2 time points. Improvement in HADS anxiety and depression scores were reported by 62.5% (362/579) relatives. SIGNIFICANCE OF RESULTS: These findings support the importance of screening relatives having risk factors of developing prolonged grief in the palliative unit and 6 months after patient's death.

The Fami-life study: protocol of a prospective observational multicenter mixed study of psychological consequences of grieving relatives in French palliative care units on behalf of the family research in palliative care (F.R.I.P.C research network).

BACKGROUND: Grieving relatives can suffer from numerous consequences like anxiety, depression, post-traumatic stress disorder (PTSD) symptoms, and prolonged grief. This study aims to assess the psychological consequences of grieving relatives after patients' death in French palliative care units and their needs for support. METHODS: This is a prospective observational multicenter mixed study. Relatives of adult patients with a neoplasia expected to be hospitalized more than 72 h in a palliative care unit for end-of-life issues will be included within 48 h after patient admission. End-of-life issues are defined by the physician at patient admission. Relatives who are not able to have a phone call at 6-months are excluded. The primary outcome is the incidence of prolonged grief reaction defined by an ICG (Inventory Complicate Grief) > 25 (0 best-76 worst) at 6 months after patient' death. Prespecified secondary outcomes are the risk factors of prolonged grief, anxiety and depression symptoms between day 3 and day 5 and at 6 months after patients' death based on an Hospital Anxiety and Depression score (range 0-42) > 8 for each subscale (minimal clinically important difference: 2.5), post-traumatic stress disorder symptoms 6 months after patient' death based on the Impact of Events Scale questionnaire (0 best-88 worst) score > 22, experience of relatives during palliative care based on the Fami-Life questionnaire, specifically built for the study. Between 6 and 12 months after the patient's death, a phone interview with relatives with prolonged grief reactions will be planned by a psychologist to understand the complex system of grief. It will be analyzed with the Interpretative Phenomenological Analysis. We planned to enroll 500 patients and their close relatives assuming a 25% prolonged grief rate and a 6-month follow-up available in 60% of relatives. DISCUSSION: This study will be the first to report the psychological consequences of French relatives after a loss of a loved one in palliative care units. Evaluating relatives' experiences can provide instrumental insights for means of improving support for relatives and evaluation of bereavement programs. TRIAL REGISTRATION: NCT03748225 registered on 11/19/2018. Recruiting patients.

High prevalence of deficient mismatch repair phenotype and the V600E BRAF mutation in elderly patients with colorectal cancer.

AIMS: Colorectal cancer (CRC) occurs mostly in the elderly. However, the biology of CRC in elderly has been poorly studied. This study examined the prevalence of deficient mismatch repair phenotype (dMMR) and BRAF mutations according to age. PATIENTS AND METHODS: MMR phenotype was prospectively determined by molecular analysis in patients of all ages undergoing surgery for CRC. BRAF V600E mutation status was analysed in a subset of dMMR tumours. RESULTS: A total of 754 patients who underwent surgery between 2005 and 2008 were included in the study. Amongst them, 272 (36%) were ≥75years old. The proportion of women <75 was 38% and that ≥75 was 53% (p<0.0001). The prevalence of dMMR was 19.4% in patients ≥75 and 10.7% in patients <75 (p=0.0017). For patients ≥75, the prevalence of dMMR was significantly higher in women than in men (27% vs 10.2%, respectively; p=0.003) but was similar in women and men <75 (12.5% vs 9.7%, respectively; p=0.4). We examined BRAF mutation status in 80 patients with dMMR tumours. The V600E BRAF mutation was significantly more frequent in patients ≥75 than in patients <75 (72.2% vs 11.4%, respectively; p<0.001). In patients ≥75, there was no difference in the prevalence of the BRAF V600E mutation according to sex (78% in women and 70% in men, p=0.9). CONCLUSIONS: The prevalence of dMMR in CRC is high in patients over 75. In elderly patients, dMMR tumours are significantly more frequent in women than in men. The BRAF mutation is frequent in elderly patients with CRC.

Diagnostic delay in a French cohort of Crohn's disease patients.

UNLABELLED: Diagnostic delay is frequent in Crohn's disease (CD) and may partly depend on socioeconomic status. The aim of this study was to determine the diagnostic delay and to identify associated risk factors, including socioeconomic deprivation in a French cohort of CD patients. METHODS: Medical and socioeconomic characteristics of all consecutive CD patients followed in 2 referral centers between September 2002 and July 2012 were prospectively recorded using an electronic database. Diagnostic delay was defined as the time period (months) from the first symptom onset to CD diagnosis. A long diagnostic delay was defined by the upper quartile of this time period. Univariate and multivariate analyses were performed to identify the baseline characteristics of patients associated with a long diagnostic delay. RESULTS: Three hundred and sixty-four patients with CD (mean age=29.2±12.6 years, 40.8% men) were analyzed. Median diagnostic delay was 5 months, and a long diagnostic delay was more than 12 months. Fifty-six patients (15.3%) had perianal lesions, and 28 patients (8.6%) had complicated disease at diagnosis. None of the following factors were associated with a long diagnostic delay: age, gender, CD location and behavior, marital and educational, language understanding, geographic origin and socioeconomic deprivation score measured by the EPICES score. CONCLUSION: In this French referral center-based cohort of CD patients, the median diagnostic delay was 5 months. None of the baseline characteristics of the CD, including socioeconomic deprivation, influenced diagnostic delay in this cohort.

Impact of complementary and alternative medicine on the quality of life in inflammatory bowel disease: results from a French national survey.

BACKGROUND: Complementary and alternative medicines (CAM) are widely used by patients with inflammatory bowel disease (IBD). Few data have been published on the impact of CAM on the quality of life (QOL). AIMS: The aim of the study was to describe CAM use in French patients with IBD, identify characteristics associated with CAM use, and assess the impact of CAM on the QOL. METHODS: We conducted an internet survey on CAM through the French IBD patient's association website. Patients had to answer a questionnaire (LimeSurvey application) about sociodemography, IBD treatment, CAM type, socioeconomic data, and QOL using the Short IBD Questionnaire (SIBDQ). Patients noted the impact of CAM on their symptoms and on their QOL on a scale of 0-100. CAM users and nonusers were compared by univariate and multivariate analyses. RESULTS: A total of 936 IBD patients responded and 767 (82.4%) filled up the whole questionnaire: 503 reported CAM use and 172 had never used. The types of CAM reported were diet-based (30.7%), body-based (25.1%), homeopathic or traditional medicine (19.6%), naturopathy (15.2%), and mind-body medicine (9.1%). The gastroenterologist was aware of CAM use in only 46% of patients. CAM users were more likely to have ulcerative colitis [odds ratio (OR)=1.78, P=0.018], clinical remission (OR=1.42, P=0.06), high level of education (OR=1.51, P=0.02), poor observance (OR=1.81, P=0.017), or to have terminated conventional treatment (OR=2.03, P=0.003). CAM users tend to have higher rates of SIBDQ scores, greater than 50 (OR=1.57, P=0.06). Improvement in symptoms and QOL was reported with all CAM types except mind medicine. CONCLUSION: CAM use is widespread among IBD patients. CAM users report improvement in symptoms and QOL, but they tend to stop their conventional treatment. Better information about CAM might improve adherence to conventional treatment.

Deficient mismatch repair phenotype is a prognostic factor for colorectal cancer in elderly patients.

OBJECTIVE: About 15% of colorectal adenocarcinomas have a deficient DNA mismatch repair phenotype. The frequency of deficient DNA mismatch repair tumours increases with age due to the hypermethylation of hMLH1 promoter. The study aimed to determine the prognostic value of deficient DNA mismatch repair phenotype in elderly patients. DESIGN: Mismatch repair phenotype was retrospectively determined by molecular analysis in consecutive resected colorectal adenocarcinoma specimens from patients over 75 years of age from 4 Oncology centres. RESULTS: 231 patients (median age: 81, range: 75-100) were enrolled from 2005 to 2008. Mean prevalence of deficient DNA mismatch repair phenotype was 22.5%, and 36% for patients over 85 years. Deficient DNA mismatch repair status was significantly associated with older age, female sex, proximal colon primary and high grade tumour. For stage II tumours no deficient DNA mismatch repair tumours had a recurrence at end of follow-up compared to 17% for tumours with proficient phenotype. The proficient phenotype status was significantly associated with worse age-adjusted overall survival [HR 2.60; 95% CI 1.05-6.44; p=0.039]. For stage III tumours a trend for less recurrence was observed for deficient DNA mismatch repair phenotype (16%) compared to proficient phenotype (36%). CONCLUSION: deficient DNA mismatch repair phenotype is a prognostic factor in stage II colorectal tumour in elderly patients. Our results suggest that mismatch repair phenotype should be taken in consideration for adjuvant chemotherapy decision in elderly patients.

Socioeconomic deprivation does not influence the severity of Crohn's disease: Results of a prospective multicenter study.

BACKGROUND: Socioeconomic deprivation is associated with poor health. The aims of this study were to evaluate the influence of deprivation in the characteristics and comparisons of deprived and nondeprived Crohn's disease (CD) patients. METHODS: CD patients were prospectively recruited from September 2006 to June 2007 in 6 hospitals in the Paris area. To assess the level of deprivation we used the EPICES score (Evaluation of Precarity and Inequalities in Health Examination Centers; http://www.cetaf.asso.fr), a validated individual index of deprivation developed in France, a score >30 defining deprivation. We defined CD as severe when at least 1 of the conventionally predefined criteria of clinical severity was present. RESULTS: In all, 207 patients (128 women and 79 men, mean age 40 years) were included and had a median score of deprivation of 20.7 (0-100). Seventy-three (35%) were deprived. There were no statistical differences between deprived and nondeprived patients for the following parameters: 1) mean age: 39 +/- 14.6 versus 40.6 +/- 13.5, P = 0.4; 2) sex ratio (female/male): 87/47 (65%) versus 41/32 (56%), P = 0.2; 3) duration of disease (years) 9 +/- 8.8 versus 8.5 +/- 7.2, P = 0.7; 4) delay from onset of symptoms to diagnosis >1 year: 22/115 (19%) versus 13/63 (21%), P = 0.8; and 5) severity of disease 71% versus 70% (P = 0.9). Nondeprived patients had a lower rate of hospitalization (40 versus 56%, P = 0,04) and a higher rate of surgery (44 versus 22%, P = 0,004); the rate of surgery was only identified by logistic regression. CONCLUSIONS: In this study deprivation does not seem to influence the severity of CD. This can be explained by easy access to healthcare in France.

Long-term follow-up and predictive factors of recurrence of anemia in a cohort of 102 very elderly patients explored for iron-deficiency anemia.

AIM: To evaluate long-term follow-up and predictors of relapse of anemia in a cohort of 102 very elderly patients previously explored for iron-deficiency anemia (IDA). METHODS: One hundred and two patients [61 women and 41 men, mean age 82+/-5.8 y (75 to 98)] explored for IDA were prospectively followed up from inclusion (June 2003 to May 2005) until death or May 2006. Survival rate was estimated by the Kaplan-Meier method and compared by the log-rank test. Predictors of recurrence of anemia were identified by multivariate analysis in the 4 following subgroups: unexplained IDA (subgroup 1, n=27), benign lesion (subgroup 2, n=37), cancer treated curatively (subgroup 3, n=28), cancers treated palliatively (subgroup 4, n=10). RESULTS: Median follow-up was 20 months. At baseline, main clinical and laboratory data were not significantly different in the 4 subgroups, especially as regards severe comorbidities. Thirty-three patients died, 10 (30%) of them in the first month. Ten (100%) belonged to subgroup 4 versus, respectively, n=7 (26%), n=8 (22%), and n=8 (29%) of patients from subgroups 1, 2, and 3 (P<0.001). No death was directly related to recurrence of anemia. Survival rate at 1 year was 10% in subgroup 4, significantly lower than the other 3 subgroups (subgroup 1: 84%; subgroup 2: 86%; subgroup 3: 78%; log-rank test, P<0.0001). Anemia recurred in 18 cases, and required red cell transfusion in 13 cases. Predictive factors of recurrence of anemia [odds ratio (confidence interval 95%), P] were cancers treated palliatively [14.9 (3-72), P<0.01] and angiodysplasias [4.5 (1.1-18.2), 0.035]. CONCLUSIONS: In a cohort of very elderly patients explored for IDA, the mortality rate and the long-term survival were not different for patients with IDA related to a cancer treated curatively than those with unexplained IDA and those with IDA related to a benign lesion. Angiodysplasias and cancers treated palliatively were associated with recurrence of anemia. These results suggest interventionist strategies (including endoscopic investigation and appropriate surgery) for elderly patients with IDA.

Management and predictors of early mortality in elderly patients with iron deficiency anemia: a prospective study of 111 patients.

OBJECTIVES: Iron deficiency anemia (IDA) is common in the elderly. It usually results from gastrointestinal (GI) bleeding and requires endoscopic exploration of the gastrointestinal tract. The aim of this prospective study in elderly patients was to evaluate the feasibility of endoscopy, the therapeutic impact, and identify predictors of early mortality. METHODS: From June 2003 to May 2005, all patients over 75 years, hospitalized for anemia were screened for iron deficiency. Clinical (including serious comorbidities), biological, endoscopic and therapeutic data were collected. One month after treatment, a follow-up was carried out to assess the tolerance of such investigation and treatment. RESULTS: One hundred and eleven patients (69 women, 82.3 +/- 6.4 years) had IDA, 102 (92%) underwent an upper endoscopy and 91 (82%) a colonoscopy. Nine (8%) patients were not investigated because of poor clinical condition (N=4) or dementia (N=5). Of the 75 (68%) patients with an identified source of bleeding, 12 (11%) had a synchronous lesion, 43 (39%) a colorectal source including 31 (72%) colorectal cancer, and 44 (40%) an upper GI source. Sixty-nine (92%) of the 75 patients received at least one of the following treatments: medical (N=27), endoscopic (N=20), and surgical (N=31). Surgery was curative in 28/31 (90%) cases of which 25/27 were colorectal cancers. One month after treatment, overall mortality was 11/111 (10%) and 4/31 (13%) after surgery. Predictors of early mortality (Odd ratio, 95% Confidence Interval) were: a malign cause (42; 3-588), no specific treatment (34; 3-423), at least 2 co-morbidities (20; 1-400). CONCLUSION: In an unselected hospitalized population of elderly patients with IDA, endoscopy was generally feasible, allowing identification of a source of bleeding, especially colorectal cancer. A specific treatment was usually possible and proved curative without increase in early mortality.

Efficacy of infliximab in Crohn's disease. Results of a retrospective multicenter study with a 15-month follow-up.

OBJECTIVES: To evaluate prescription practices and response to infliximab treatment for Crohn's disease (CD). PATIENTS AND METHODS: The files of CD patients treated with at least one infusion of infliximab treated in gastroenterology units belonging to university teaching hospitals of the Parisian hospitals group (Assistance Publique-Hôpitaux de Paris (AP-HP) during the year 2000 were analyzed retrospectively. RESULTS: One hundred and thirty-seven patients (36.0 +/- 12.7 years, 92 females) from 12 centers were studied. Indication for treatment was fistulae or perianal disease in 39% of patients, active Crohn's disease in 45% and mixed conditions in 16%. Mean follow-up was 15.2 +/- 7.2 months. The overall response rate was 85%. No predictive factor of sustained remission could be identified. The mean time to relapse was to 3.9 +/- 3.1 months. Thirty-eight patients were on maintenance therapy at the end of the follow up; 37% exhibiting progressive lost of response to treatment. Immunosuppressive therapy was added to infliximab in 78% of cases but response to infliximab was not modified by addition of immunosuppressive drugs. Adverse events, most frequently minor, were noted in 23% of the patients. CONCLUSION: This retrospective study confirms the efficacy and safety of infliximab in CD.