Cure of cancer for seven cancer sites in the Flemish Region.

Cumulative relative survival curves for many cancers reach a plateau several years after diagnosis, indicating that the cancer survivor group has reached "statistical" cure. Parametric mixture cure model analysis on grouped relative survival curves provide an interesting way to determine the proportion of statistically cured cases and the mean survival time of the fatal cases in particular for population-based cancer registries. Based on the relative survival data from the Belgian Cancer Registry, parametric cure models were applied to seven cancer sites (cervix, colon, corpus uteri, skin melanoma, pancreas, stomach and oesophagus), at the Flemish Regional level for the incidence period 1999-2011. Statistical cure was observed for the examined cancer sites except for oesophageal cancer. The estimated cured proportion ranged from 5.9% [5.7, 6.1] for pancreatic cancer to 80.8% [80.5, 81.2] for skin melanoma. Cure results were further stratified by gender or age group. Stratified cured proportions were higher for females compared to males in colon cancer, stomach cancer, pancreas cancer and skin melanoma, which can mainly be attributed to differences in stage and age distribution between both sexes. This study demonstrates the applicability of cure rate models for the selected cancer sites after 14 years of follow-up and presents the first population-based results on the cure of cancer in Belgium.

Do patients diagnosed with Alzheimer's disease benefit from a psycho-educational programme for family caregivers? A randomised controlled study.

OBJECTIVE: The Aide dans la Maladie d'Alzheimer (AIDMA) study was conducted to determine whether a psycho-educational programme (PEP) for primary caregivers in addition to standard anti-dementia drugs for patients improves caregivers' psychological condition and patients' activities of daily life. METHOD: Multicentre randomised controlled intervention trial. One hundred and sixty-seven dyads 'patient-caregiver' were recruited from 15 French memory clinics and randomised in two parallel groups. The intervention group was offered the PEP in 12 group sessions for 3 months. The control group had usual care. Patients in both groups with mild to moderate Alzheimer's disease (AD) were diagnosed and treated with pharmacotherapy. Patients' primary efficacy variable was functional status assessed with the Disability Assessment Scale for Dementia (DAD) scale. Alzheimer Disease Assessment Scale (ADAS-Cog) and Neuropsychiatric Inventory (NPI) were secondary criteria. Caregivers' first outcome measure was depressive symptoms assessed with the Montgomery and Asberg Depression Rating Scale (MADRS) scale. Zarit scale, Sense of Competence Questionnaire (SCQ) and Visual Analogue Scales (VAS) were secondary criteria. Assessment was done at baseline, 3 months (M3, end of intervention) and 6 months (M6). RESULTS: Patients' stabilisation was observed in both groups. In caregivers, significant improvement in disease understanding at M3 (p = 0.007) and M6 (p = 0.0001) and in ability to cope with care-recipients' disease at M6 (0.02) was evidenced. CONCLUSION: The PEP had no additional impact on patients but carers developed more effective disease understanding and ability of coping. Results support the idea that the PEP although improving caregivers' condition is not sufficient to improve patients' activities in daily life which requires additional individually tailored interventions provided by professionals.

Development and Validation of a Model to Identify Alzheimer's Disease and Related Syndromes in Administrative Data.

BACKGROUND: Administrative data are used in the field of Alzheimer's Disease and Related Syndromes (ADRS), however their performance to identify ADRS is unknown. OBJECTIVE: i) To develop and validate a model to identify ADRS prevalent cases in French administrative data (SNDS), ii) to identify factors associated with false negatives. METHODS: Retrospective cohort of subjects ≥ 65 years, living in South-Western France, who attended a memory clinic between April and December 2013. Gold standard for ADRS diagnosis was the memory clinic specialized diagnosis. Memory clinics' data were matched to administrative data (drug reimbursements, diagnoses during hospitalizations, registration with costly chronic conditions). Prediction models were developed for 1-year and 3-year periods of administrative data using multivariable logistic regression models. Overall model performance, discrimination, and calibration were estimated and corrected for optimism by resampling. Youden index was used to define ADRS positivity and to estimate sensitivity, specificity, positive predictive and negative probabilities. Factors associated with false negatives were identified using multivariable logistic regressions. RESULTS: 3360 subjects were studied, 52% diagnosed with ADRS by memory clinics. Prediction model based on age, all-cause hospitalization, registration with ADRS as a chronic condition, number of anti-dementia drugs, mention of ADRS during hospitalizations had good discriminative performance (c-statistic: 0.814, sensitivity: 76.0%, specificity: 74.2% for 2013 data). 419 false negatives (24.0%) were younger, had more often ADRS types other than Alzheimer's disease, moderate forms of ADRS, recent diagnosis, and suffered from other comorbidities than true positives. CONCLUSION: Administrative data presented acceptable performance for detecting ADRS. External validation studies should be encouraged.

Can metabolic abnormalities after a fall predict short term mortality in elderly patients?

Morbidity related is important in older adults who fall and are consequently referred to emergency departments (ED). The aim of this study is to determine 6-month all-causes mortality in patients over 75 years referred to an emergency department after a fall at home, and to define the criteria associated with death. The design was a prospective observational study with a 6-month follow-up in an Emergency Department of a tertiary teaching hospital, Paris, France. We included for a 6-month period patients over 75 years who visited the Emergency Department for a fall that occurred at home and measured the 6-month all-causes mortality. Uni- and multivariate assessment of factors related to mortality were adjusted for the occurrence of trauma. We enrolled 433 patients. Mean age was 86 years and two-thirds were women. The population was in relatively good health and preserved autonomy. The prevailing consequence was trauma and 11% had metabolic disorders. 64 patients (15%) died within 6 months. Factors associated with mortality included decrease in Katz score, male gender, a fall of intrinsic origin and the occurrence of adverse metabolic events. Markers of fragility such as poor previous level of autonomy, clinical disorders and metabolic abnormalities, as cause or consequence, indicate a potentially poor outcome more than the presence of severe trauma. As metabolic abnormalities can be an indirect marker of a long delay before emergency medical care, this study underscored the importance of early warning system for the frailest old individuals in order to prevent such complications.

Do ED staffs have a role to play in the prevention of repeat falls in elderly patients?

BACKGROUND: Fall-related morbidity is a serious public health issue in older adults referred to emergency departments (EDs). Emergency physicians mostly focus on immediate injuries, whereas the specific assessment of functional consequences and opportunities for prevention remain scarce. The aim of this study was to determine the factors influencing 6-month independence. METHODS: We used a prospective observational study at the ED of a tertiary teaching hospital over a 6-month period. Uni- and multivariate assessments of factors related to loss of independence were examined. RESULTS: A total of 367 patients survived to 6 months, mean age was 86 years, and 79% were women. The population was initially healthy and independent. Because this independence reassured the medical staff, more than 42% percent were directly discharged home without any improvement of home facilities; only 63% had recovered their independence at the end of the follow-up. There were 111 patients were hospitalized for 30 days or more. Older patients, initial Katz score, and absence of immediate trauma consequences were associated with an increased risk for loss of independence. CONCLUSIONS: Because prevention is an emerging role of ED, a multidisciplinary team should evaluate fallers and propose medical and environmental changes as required for those discharged after their ED visit.

Use of health insurance data to identify and quantify the prevalence of main comorbidities in lung cancer patients.

BACKGROUND: Identifying comorbidities in lung cancer patients is a complex process in population-based studies and no gold standard exists. The current study aims to identify and measure the main comorbidities using administrative health insurance data, which were available on a population-based level. METHOD: A literature search was conducted to identify comorbidities in lung cancer patients and to select Anatomical Therapeutic Chemical codes to measure them. For each patient, the volume of delivered relevant drugs for each comorbidity in the year preceding the diagnosis of lung cancer was computed, based on the Defined Daily Doses reimbursed. Case definition rules were set by comparing the identification of comorbidities via health insurance data with the reporting of them in the medical files in a sample of hospitals. RESULTS: Four comorbidities were identified: chronic respiratory diseases, chronic cardiovascular diseases, diabetes mellitus and renal diseases. A very good to moderate agreement between the prevalence based on medical files versus health insurance data was obtained for diabetes mellitus (kappa = 0.83), chronic cardiovascular diseases (kappa = 0.64), chronic respiratory diseases (kappa = 0.48) but not for renal diseases (kappa = 0.22). Because only 27% of patients having renal diseases recorded in the medical files were identified using health insurance data, this comorbidity was not withheld. Among 12,839 lung cancer patients diagnosed in 2010-2011 in Belgium, 29.7% had chronic respiratory diseases, 57.5% had chronic cardiovascular diseases and 14.1% had diabetes mellitus. DISCUSSION: This study showed that it was possible to capture three major comorbidities in lung cancer patients using administrative health data, namely, diabetes mellitus, chronic cardiovascular diseases, and chronic respiratory diseases. However, the agreement was only moderate for the last one. A prerequisite for using this methodology is that administrative health data are available for all patients.

Seasonal variation in cutaneous melanoma incidence, link with recent UV levels: a population-based study in Belgium (2006-2011).

Our objective was to test the hypothesis of a short-term late-promoting effect of ultraviolet (UV) exposure on the development of cutaneous melanoma as an explanation for the summer peak in melanoma incidence. Therefore, we studied seasonal variation in melanoma incidence in relation to recent UV levels by direct UV measurements. Data from the Belgian Cancer Registry on invasive cutaneous melanoma diagnosed during 2006-2011 were used for analysis. Daily data on UV measurements in Belgium were obtained from the Royal Meteorological Institute. Simple and multiple negative binomial regression models were used to investigate the influence of recent UV levels on melanoma incidence. The sum of the mean UV doses in the 2 months before diagnosis was used as a proxy for recent UV exposure in the population. To include variable sunburn risks during the year, the categorical variable 'semester' was created. The incidence of melanoma in Belgium shows a distinct seasonal variation, with peaks in June or July. We found that part of this variation could be explained by the variation in dermatologic activity and, therefore, used this as an offset in our models. We found a linear relationship between melanoma incidence and UV dose in the 2 months preceding the diagnosis. UV levels had more impact in the first semester. The effect of UV levels was not modified by sex nor age. The interaction between anatomical site and UV levels was significant (P=0.002) and showed a higher effect on the upper and lower limbs compared with the head and neck and trunk.

Is melanoma survival influenced by month of diagnosis?

BACKGROUND: Despite being a well-documented phenomenon, seasonal variation in the incidence of cutaneous melanoma is poorly understood, and data on the seasonality of melanoma survival are scarce. We sought to explore the seasonal variation in melanoma incidence and survival in Belgium and to assess the characteristics and outcomes of cases diagnosed during the seasonal peak. METHODS: All cases of invasive cutaneous melanoma-patients over 15 years of age and registered by the Belgian Cancer Registry (BCR) from 2004 to 2009-were included (n=9782). Monthly variations in incidence were estimated by the ratio of the number of cases diagnosed each month to that diagnosed in January (Rmonth/January) using Nam's method. The observed and relative 5-year survival rates were adjusted on patient and tumour characteristics using Cox proportional hazards regression models and generalised linear models with a Poisson error structure, respectively. RESULTS: A peak in melanoma incidence was observed in June (RJune/January=1.64, 95% confidence interval (CI)=1.54-1.73). The 5-year observed survival (OS) and relative survival (RS) rates were significantly higher for patients diagnosed in June compared with other months (OSJune=84%, 95%CI=81-86 versus OSOthermonths=79%, 95%CI=78-80; RSJune=93%, 95%CI=90-95 versus RSothermonths=87%, 95%CI=86-88). After adjustment, the 5-year OS remained significantly higher for patients diagnosed in June (hazard ratioJune=0.78, 95%CI=0.62-0.98); however, the 5-year RS was no longer significantly different for patients diagnosed in June compared with other months (relative excess riskJune=1.16, 95%CI=0.73-1.84). CONCLUSIONS: This study demonstrated a seasonal variation in melanoma incidence in Belgium with a peak in June for the period 2004-2009. When adjusted for patient and tumour characteristics, patients diagnosed in June had higher observed survival rates, but relative survival rates did not differ. Our findings do not support an influence of season of diagnosis on melanoma prognosis.

Does a central review platform improve the quality of radiotherapy for rectal cancer? Results of a national quality assurance project.

BACKGROUND AND PURPOSE: Quality assurance (QA) for radiation treatment has become a priority since poorly delivered radiotherapy can negatively influence patient outcome. Within a national project we evaluated the feasibility of a central review platform and its role in improving uniformity of clinical target volume (CTV) delineation in daily practice. MATERIAL AND METHODS: All Belgian radiotherapy departments were invited to participate and were asked to upload CTVs for rectal cancer treatment onto a secured server. These were centrally reviewed and feedback was given per e-mail. For each five consecutive patients per centre, the overlap parameter dice coefficient (DC) and the volumetric parameters volumetric ratio (RV) and commonly contoured volume (VCC) were calculated. RESULTS: Twenty departments submitted 1224 eligible cases of which 909 were modified (74.3%). There was a significant increase in RV and VCC between the first ten patients per centre and the others. This was not seen for DC. Statistical analysis did not show a further significant improvement in delineation over the entire review period. CONCLUSION: Central review was feasible and increased the uniformity in CTV delineation in the first ten rectal cancer patients per centre. The observations in this study can be used to optimize future QA initiatives.

Accuracy of C-reactive protein, procalcitonin, and mid-regional pro-atrial natriuretic peptide to guide site of care of community-acquired pneumonia.

BACKGROUND: The use at bedside of C-reactive protein (CRP), procalcitonin (PCT) or mid-regional pro-atrial natriuretic peptide (ANP) has been advocated to help management of patients with community-acquired pneumonia (CAP) in emergency medicine. OBJECTIVE: To assess the effectiveness of CRP, PCT, and ANP measures in assisting emergency physicians deciding hospital admission for CAP with low risk of complication. DESIGN: Multicenter, prospective, observational study with blind evaluation. SETTING: Emergency departments of 12 French hospitals. PATIENTS: Five hundred forty-nine consecutive, immunocompetent adult patients with mild CAP. MEASUREMENTS: Centralized and blind measure of baseline CRP, PCT, and ANP; sensitivity, specificity, and positive and negative likelihood ratios for determining hospital admission. Gold standard for admission was defined by experts' advice combined with admission requirement or death at 28 days. Optimal threshold values were determined by receiver operating characteristic (ROC) curves, and area under curve (AUC) of the three biomarkers was compared. RESULTS: According to gold standard, 310 (56%) patients required admission and 239 (44%) needed to be discharged. PCT and ANP levels increased with Pneumonia Severity Index risk categories. ANP (AUC 0.76 [95% CI 0.72-0.80]) more accurately predicted admission requirement than did PCT (AUC 0.65 [95% CI 0.61-0.70]) or CRP (AUC 0.59 [95% CI 0.54-0.64]) (both p values <0.01). We determined that 135 pmol/L was a threshold for ANP level to discriminate admission requirement (positive likelihood ratio 7.45 [95% CI 4.22-8.16]). CONCLUSIONS: In a selected population of CAP with low risk of complication, a single ANP measurement was more accurate than CRP and PCT to predict appropriate admission. These results should be confirmed by additional studies.

Effect of sublingual administration of interferon-alpha on the immune response to influenza vaccination in institutionalized elderly individuals.

A randomized double-blind placebo-controlled study was conducted to determine the effect of sublingual administration of IFNalpha on the immune response to influenza vaccination in elderly institutionalized individuals. Sublingual administration of 10 million IU of IFNalpha immediately prior to vaccination, reduced the geometric mean haemagglutination inhibitory (HAI) and IgG2 circulating antibody titers, and the secretory IgA (sIgA) response in saliva, to the New York strain of influenza A virus, 21 days post-vaccination, without detectable drug-related local or systemic toxicity. IFN treatment did not inhibit the immune response to the other components of the vaccine; the New Caledonia strain of influenza A virus, or the Jiangsu strain of influenza B virus. At the dose tested sublingual administration of IFNalpha reduces the immune response to influenza vaccination in elderly institutionalized individuals.

Immunological efficacy of a three-dose schedule of hepatitis A vaccine in HIV-infected adults: HEPAVAC study.

BACKGROUND: The immunogenicity of vaccines, including vaccine against hepatitis A virus (HAV), is impaired in patients with HIV infection, requiring revised immunization regimens. METHODS: We evaluated the immunological efficacy and safety of a 3-dose schedule of hepatitis A vaccine in HIV-infected adults. HAV-seronegative HIV-infected adults were randomized to receive either 3 doses of 1440 UI of hepatitis A vaccine (HAVRIX; GlaxoSmithKline, Marly le Roi, France) at weeks 0, 4, and 24 (46 patients) or 2 doses 24 weeks apart (49 patients). RESULTS: At week 28, seroconversion, defined as an anti-HAV antibody >or=20 mIU/mL, occurred in 82.6% and 69.4% of patients in the 3-dose and the 2-dose group, respectively (P = 0.13, intent-to-treat analysis, missing data = nonresponder), and in 88.4% and 72.3% of patients in the 3-dose and the 2-dose group, respectively (P = 0.06, observed analysis). Only 37.9% of patients experienced seroconversion after 1 vaccine dose (intent-to-treat analysis). Anti-HAV antibody geometric mean titers were 323 and 132 mIU/mL in the 3-dose group and 138 and 67 mIU/mL in the 2-dose group, respectively, 28 (P = 0.03) and 72 weeks (P = 0.05) after the first vaccine dose. There were no serious adverse events associated with the vaccine. Multivariate analysis showed no treatment group effect but indicated that absence of tobacco smoking (odds ratio = 2.92, 95% confidence interval: 1.07 to 7.97; P = 0.04) was an independent predictor of response to HAV vaccine. CONCLUSIONS: In HIV-infected adults, immunogenicity of hepatitis A vaccine is poor. Three doses of vaccine were safe and increased antibody titers.