The Ambulatory Medical Assistance (AMA) programme during active-phase treatment in patients with haematological malignancies: A cost-effectiveness analysis.

CONTEXT: The need for patient navigator is growing, and there is a lack of cost evaluation, especially during survivorship. OBJECTIVE: The objective of this study is to evaluate the cost-effectiveness of an Ambulatory Medical Assistance (AMA) programme in patients with haematological malignancies (HM). DESIGN: A cost-effectiveness analysis of the AMA programme was performed compared to a simulated control arm. SETTING: An interventional, single-arm and prospective study was conducted in a French reference haematology-oncology centre between 2016 and 2020. PARTICIPANTS: Adult patients were enrolled with histologically documented malignant haematology, during their active therapy phase, and treated either by intravenous chemotherapy or oral therapy. METHODS: An extrapolation of the effectiveness was derived from a similar nurse monitoring programme (CAPRI study). Cost effectiveness of the programme was evaluated through adverse events of Grade 3 or 4 avoided in different populations. RESULTS: Included patient (n = 797) from the AMA programme were followed during 125 days (IQR: 0-181), and adverse events (Grade 3/4) were observed in 10.1% of patients versus 13.4% in the simulated control arm. The overall cost of AE avoided was estimated to €81,113, leading to an ICER of €864. CONCLUSION: The AMA programme was shown to be cost-effective compared to a simulated control arm with no intervention.

Pattern of Clinical Progression Until Metastatic Castration-Resistant Prostate Cancer: An Epidemiological Study from the European Prostate Cancer Registry.

BACKGROUND: Prostate cancer (PCa) is the most frequently diagnosed cancer in men in Europe. The impact of PCa natural history and therapeutic management on the outcomes of castration-resistant prostate cancer patients with metastasis (mCRPC) remains unclear. OBJECTIVE: The objective of this study was to describe retrospectively patterns of clinical progression through diagnosis sequences before the mCRPC stage and to assess how these sequences impacted patients' disease progression and overall survival at mCRPC stage. PATIENTS AND METHODS: Patients with mCRPC were identified from the Prostate Cancer Registry (PCR), an observational study in a real-world setting in 16 countries between 2013 and 2016. Patients were grouped in diagnosis sequences before mCRPC and defined by date of PCa diagnosis, first metastasis, and castration resistance. Distribution of time-to-event variables were estimated using Kaplan-Meier product-limit survival curves for overall survival (OS) and progression-free survival (PFS). Non-adjusted Cox models were conducted for efficacy endpoints (OS, PFS) to estimate hazard ratios between diagnosis sequences. RESULTS: At the end of study, 2859 mCRPC patients were included in this analysis. Among mCRPC four diagnosis sequences were identified: 35% developed metastases (mHSPC) before becoming castration resistant (sequence 1, metachronous mHSPC), 10% developed castration resistance (nmCRPC) before metastases (sequence 2), 27% developed metastases and castration resistance within 4 months (sequence 3) and 28% of patients were de novo mHSPC (sequence 4). Median OS was 17.7 months (interquartile range (IQR): 8.8-29.9) and PFS was 6.4 months (IQR: 3.2-12.0). The univariate analyses showed no correlation between mCRPC patients' OS or PFS and the diagnosis sequence. CONCLUSION: This large European study describe four different patterns of prostate cancer progression to mCRPC stage. Our results indicate that patient survival becomes comparable after progression to mCRPC, regardless of the diagnosis sequence. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02236637; registered September 2014.

Dalbavancin in Real Life: Economic Impact of Prescription Timing in French Hospitals.

INTRODUCTION: The extended half-life of dalbavancin justifies a once-a-week dosing schedule and is supposed to favour early discharge. These advantages may therefore compensate for the cost of dalbavancin, but no real-life assessment has been conducted to date. We aimed to assess the real-life budget impact of dalbavancin through its impact on the length of stay in French hospitals. METHODS: A multicentre cohort based on the French registry of dalbavancin use in 2019 was compared to the French national discharge summary database. Lengths of stay and budget impact related to the infection type, the time of introduction of dalbavancin, the type of catheter and patient subgroups were assessed. An early switch was defined when dalbavancin was administered as the first or second treatment and within less than 11 days of hospitalization. RESULTS: A total of 179 patients were identified in the registry, and 154 were included in our study. Dalbavancin was mostly used for bone and joint infections (56.0%), infective endocarditis (19.0%) and acute bacterial skin and skin structure infections (6.0%). When compared to the data for similar patients in the national database, the length of stay was almost always shorter for patients treated with dalbavancin (up to a reduction of 13 days). The budget impact for dalbavancin was heterogeneous but frequently generated savings (up to 2257.0 €). Early switching (within less than 11 days) was associated with savings (or lesser costs), with even greater benefits within 7 days of hospitalization. Patients who required a deep venous catheter as well as the most severe patients benefited the most from dalbavancin. CONCLUSION: Our study confirms that dalbavancin is associated with early discharge, which can offset its cost and generate savings. The greatest benefit is achieved with an early switch.

Author Correction: A stochastic agent-based model of the SARS-CoV-2 epidemic in France.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A stochastic agent-based model of the SARS-CoV-2 epidemic in France.

Many European countries have responded to the COVID-19 pandemic by implementing nationwide protection measures and lockdowns1. However, the epidemic could rebound when such measures are relaxed, possibly leading to a requirement for a second or more, repeated lockdowns2. Here, we present results of a stochastic agent-based microsimulation model of the COVID-19 epidemic in France. We examined the potential impact of post-lockdown measures, including physical distancing, mask-wearing and shielding individuals who are the most vulnerable to severe COVID-19 infection, on cumulative disease incidence and mortality, and on intensive care unit (ICU)-bed occupancy. While lockdown is effective in containing the viral spread, once lifted, regardless of duration, it would be unlikely to prevent a rebound. Both physical distancing and mask-wearing, although effective in slowing the epidemic and in reducing mortality, would also be ineffective in ultimately preventing ICUs from becoming overwhelmed and a subsequent second lockdown. However, these measures coupled with the shielding of vulnerable people would be associated with better outcomes, including lower mortality and maintaining an adequate ICU capacity to prevent a second lockdown. Benefits would nonetheless be markedly reduced if most people do not adhere to these measures, or if they are not maintained for a sufficiently long period.

Facing the COVID-19 epidemic in NYC: a stochastic agent-based model of various intervention strategies.

Global spread of coronavirus disease 2019 (COVID-19) has created an unprecedented infectious disease crisis worldwide. Despite uncertainties about COVID-19, model-based forecasting of competing mitigation measures on its course is urgently needed to inform mitigation policy. We used a stochastic agent-based microsimulation model of the COVID-19 epidemic in New York City and evaluated the potential impact of quarantine duration (from 4 to 16 weeks), quarantine lifting type (1-step lifting for all individuals versus a 2-step lifting according to age), post-quarantine screening, and use of a hypothetical effective treatment against COVID-19 on the disease's cumulative incidence and mortality, and on ICU-bed occupancy. The source code of the model has been deposited in a public source code repository (GitHub®). The model calibrated well and variation of model parameter values had little impact on outcome estimates. While quarantine is efficient to contain the viral spread, it is unlikely to prevent a rebound of the epidemic once lifted. We projected that lifting quarantine in a single step for the full population would be unlikely to substantially lower the cumulative mortality, regardless of quarantine duration. By contrast, a two-step quarantine lifting according to age was associated with a substantially lower cumulative mortality and incidence, up to 71% and 23%, respectively, as well as lower ICU-bed occupancy. Although post-quarantine screening was associated with diminished epidemic rebound, this strategy may not prevent ICUs from being overcrowded. It may even become deleterious after a 2-step quarantine lifting according to age if the herd immunity effect does not had sufficient time to become established in the younger population when the quarantine is lifted for the older population. An effective treatment against COVID-19 would considerably reduce the consequences of the epidemic, even more so if ICU capacity is not exceeded.

Lockdown exit strategies and risk of a second epidemic peak: a stochastic agent-based model of SARS-CoV-2 epidemic in France.

Most European countries have responded to the COVID-19 threat by nationwide implementation of barrier measures and lockdown. However, assuming that population immunity will build up through the epidemic, it is likely to rebound once these measures are relaxed, possibly leading to a second or multiple repeated lockdowns. In this report, we present results of epidemiological modelling that has helped inform policy making in France. We used a stochastic agent-based microsimulation model of the COVID-19 epidemic in France, and examined the potential impact of post-quarantine measures, including social distancing, mask-wearing, and shielding of the population the most vulnerable to severe COVID-19 infection, on the disease's cumulative incidence and mortality, and on ICU-bed occupancy. The model calibrated well and variation of model parameter values had little impact on outcome estimates. While quarantine is effective in containing the viral spread, it would be unlikely to prevent a rebound of the epidemic once lifted, regardless of its duration. Both social distancing and mask-wearing, although effective in slowing the epidemic and in reducing mortality, would also be ineffective in ultimately preventing the overwhelming of ICUs and a second lockdown. However, these measures coupled with shielding of vulnerable people would be associated with better outcomes, including lower cumulative incidence, mortality, and maintaining an adequate number of ICU beds to prevent a second lockdown. Benefits would nonetheless be markedly reduced if these measures were not applied by most people or not maintained for a sufficiently long period, as herd immunity progressively establishes in the less vulnerable population.

Blood pressure variability and risk of dementia in an elderly cohort, the Three-City Study.

BACKGROUND: The relationship between blood pressure and dementia is incompletely understood in elderly individuals. Blood pressure variability may have a role in the risk of dementia. METHODS: This investigation was a cohort study of 6506 elderly individuals followed-up for 8 years (1999-2001 through 2008) with assessments at years 2, 4, and 7-8. Blood pressure was measured by electronic devices at baseline and at 2- and 4-year follow-up examinations. Cox proportional hazard models adjusted for potential confounders were used to estimate the risk of incident dementia according to blood pressure (means and coefficients of variation of the three measures). RESULTS: During the 40,151 person-years of follow-up 474 participants developed dementia. We observed no association between mean blood pressure and risk of dementia. In contrast, an increase of 1 standard deviation in the coefficient of variation of blood pressure was associated with a 10% increased risk of dementia. Analysis by deciles of the coefficient of variation showed that the higher the variability, the higher the risk of dementia (P<.02 for trend). In the fully adjusted Cox model, the risk of dementia for those in the highest decile of the coefficient of variation of systolic blood pressure was 1.77 (1.17-2.69) compared with the lowest decile. CONCLUSIONS: In this cohort study, variability of blood pressure during follow-up was associated with an increased risk of incident dementia, whereas mean blood pressure was not. Limitation of blood pressure fluctuation may be an important target to preserve cognitive function in the elderly.

Factors associated with radiographic lesions in early axial spondyloarthritis. Results from the DESIR cohort.

OBJECTIVE: To assess whether factors such as inflammation by laboratory tests and MRI differ between early axial SpA with and without radiographic lesions. METHODS: Cross-sectional analysis of baseline data from Devenir des Spondylarthropathies Indifferenciées Récentes (DESIR) cohort patients having recent-onset inflammatory back pain and meeting Assessment of SpondyloArthritis international Society criteria. The baseline evaluation included radiographs and MRI of the SI joints (SIJs) and spine. Patients were classified as having radiographic lesions if they had at least one obvious sacroiliitis, grade 2 for at least one vertebral corner or grade 1 for at least two vertebral corners (at the cervical or lumbar level, according to the modified Stoke Ankylosing Spondylitis Spine Score). Associations between baseline characteristics and the presence of radiographic lesions were evaluated by estimating multi-adjusted odd ratios (aORs) and their 95% CIs using a logistic regression model. RESULTS: Of 475 patients, 180 (37.9%) had radiographic lesions. Factors positively associated with radiographic lesions were alcohol use (aOR 2.42; 95% CI 1.31, 4.44; P = 0.005), CRP level (aOR 1.44; 95% CI 1.13, 1.84; P = 0.003) and SIJ inflammation by MRI (aOR 2.25; 95% CI 1.40, 3.60; P = 0.001); negative associations occurred with good NSAID responsiveness (aOR 0.44; 95% CI 0.24, 0.81; P = 0.008); spinal MRI inflammation was associated with radiographic lesions only in smokers (aOR 1.99; 95% CI 1.01, 3.92; P = 0.048). CONCLUSION: Alcohol use, poor responsiveness to NSAIDs, CRP elevation, SIJ MRI inflammation and spinal MRI inflammation in smokers were independently associated with radiographic lesions in early axial SpA.

The burden of liver disease in Europe: a review of available epidemiological data.

To survey the burden of liver disease in Europe and its causes 260 epidemiological studies published in the last five years were reviewed. The incidence and prevalence of cirrhosis and primary liver cancer are key to understand the burden of liver disease. They represent the end-stage of liver pathology and thus are indicative of the associated mortality. About 0.1% of Hungarian males will die of cirrhosis every year compared with 0.001% of Greek females. WHO estimate that liver cancer is responsible for around 47,000 deaths per year in the EU. Harmful alcohol consumption, viral hepatitis B and C and metabolic syndromes related to overweight and obesity are the leading causes of cirrhosis and primary liver cancer in Europe. Chronic hepatitis B affects 0.5-0.7% of the European population. In the last decade the prevalence of chronic hepatitis C was 0.13-3.26%. It is of great concern that about 90% of people in Europe infected by viral hepatitis are unaware of their status. Available data suggest the prevalence rate of NAFLD is 2-44% in the general European population (including obese children) and 42.6-69.5% in people with type 2 diabetes. Each of these four major causes of liver disease is amenable to prevention and treatment, reducing the burden of liver disease in Europe and saving lives. Further surveys are urgently needed to implement cost-effective prevention programmes and novel treatments to tackle this problem.

Does the site of magnetic resonance imaging abnormalities match the site of recent-onset inflammatory back pain? The DESIR cohort.

OBJECTIVES: To assess whether the site of axial pain (thoracic spine, lumbar spine or buttock(s)) was associated with the site of MRI lesions in patients with recent inflammatory back pain (IBP) suggesting spondyloarthritis. METHODS: We conducted a cross-sectional study of baseline data in 708 patients with recent IBP from the DESIR cohort. Radiographs of the sacroiliac joints (SIJs) and MRI scans of the SIJs and thoracic and lumbar spine were obtained routinely. Associations between pain sites and sites of inflammatory and structural MRI changes were evaluated using separate multivariate logistic regressions. RESULTS: Of the 648 patients with complete data, 61% had thoracic pain, 91.6% lumbar pain and 79.2% buttock pain. MRI inflammation was seen in 19%, 21% and 46% of patients at the thoracic, lumbar and SIJ sites, respectively. By multivariate analysis, pain was significantly associated with MRI inflammation only at the same site (adjusted OR (aOR)thoracic pain 1.71; 95% CI 1.09 to 2.67; p=0.02; aORlumbar pain 2.53; 95% CI 1.03 to 6.20; p=0.04; aORbuttock pain 2.86; 95% CI 1.84 to 4.46; p<0.0001). Pain site was not significantly associated with the site of structural MRI changes, except for buttock pain and SIJ structural MRI changes (aORbuttock pain 1.89; 95% CI 1.22 to 2.90; p=0.004). The association between pain site and site of MRI inflammation persisted in the subgroups with normal or doubtful SIJ radiographs or with Assessment of SpondyloArthritis international Society criteria for axial spondyloarthritis. CONCLUSIONS: The site of pain (thoracic spine, lumbar spine or buttock(s)) is associated with MRI inflammation at the same site in patients with recent IBP.

Excessive daytime sleepiness and vascular events: the Three City Study.

OBJECTIVE: We assessed whether excessive daytime sleepiness (EDS) at baseline was associated with subsequent coronary heart disease (CHD) and stroke events. METHODS: The Three City Study, a French population-based multicenter prospective study, included 7,007 subjects aged ≥65 years with no personal history of CHD, stroke, or dementia, and self-rated EDS as never, rare, regular, or frequent in response to a face-to-face questionnaire. Hazard ratios (HRs) for the first episode of stroke and CHD over 6 years were estimated using a Cox proportional hazards model with age as the time scale. RESULTS: The mean age of the cohort was 73.7 years (standard deviation, 5.37), 63% were women, and 13.3% and 4.3% reported regular and frequent EDS, respectively. After a median follow-up period of 5.1 years, 372 subjects experienced a first event, either stroke (122 subjects) or a CHD event (250 subjects). The increased risk of CHD and stroke was confined to the group with frequent EDS, and was 1.73× as much as in the group that reported never having EDS (HR, 1.73; 95% confidence interval [CI], 1.15-2.60), after adjustment for confounding and mediating factors. This association was seen in those without hypertension but not in those with hypertension at baseline (p for interaction = 0.01). Moreover, the association with frequent EDS was statistically significant for stroke (HR, 2.10; 95% CI, 1.13-3.89) but not for CHD (HR, 1.51; 95% CI, 0.87-2.61). INTERPRETATION: The current study suggests that frequent EDS is independently associated with future vascular events and stroke in particular in healthy community-dwelling elderly subjects.