Population health management in France: specifying population groups through the DRG system.

BACKGROUND: Population health management (PHM) by hospital groups is not yet defined nor implemented in France. However, in 2019, the French Hospitals Federation launched a pilot program to experiment PHM in five territories around five Territorial Hospital Groups (GHT's). In order to implement PHM, it is necessary to firstly define the population which healthcare facilities (hospitals) have responsibility for. In the French healthcare system, mapping of health territories however relies mainly on administrative data criteria which do not fit with the actual implementation of GHT's. Mapping for the creation of territorial hospital groups (GHTs) also did not include medical criteria nor all healthcare offers particularly in private hospitals and primary care services, who are not legally part of GHT's but are major healthcare providers. The objective of this study was to define the French population groups for PHM per hospital group. METHODS: A database study based on DRG (acute care, post-acute and rehabilitation, psychiatry and home care) from the French National Hospitals Database was conducted. Data included all hospital stays from 1 January 2016 to 31 December 2017. The main outcome of this study was to create mutually exclusive territories that would reflect an accurate national healthcare service consumption. A six-step method was implemented using automated analysis reviewed manually by national experts. RESULTS: In total, 2840 healthcare facilities, 5571 geographical zones and 31,441,506 hospital stays were identified and collated from the database. In total, 132 GHTs were included and there were 72 zones (1.3%) allocated to a different GHTs. Furthermore, 200 zones were manually reviewed with 33 zones allocated to another GHT. Only one area did not have a population superior to 50,000 inhabitants. Three were shown to have a population superior to 2 million. CONCLUSIONS: Our study demonstrated a feasible methodology to define the French population under the responsibility of 132 hospital groups validated by a national group of experts.

Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) HEPAVIH CO13 cohort].

OBJECTIVES: The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. METHODS: The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). RESULTS: Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naïve patients. CONCLUSIONS: Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders.

HCV viral load at baseline and at week 4 of telaprevir/boceprevir based triple therapies are associated with virological outcome in HIV/hepatitis C co-infected patients.

BACKGROUND: As first generation HCV-specific protease inhibitors, boceprevir (BOC) or telaprevir (TVR) can achieve 60% to 70% sustained virological response (SVR) for HCV infected patients with genotype 1 infections, they could remain temporary a therapeutic option in patients living in resources limited countries with limited access to the new anti-HCV direct acting antiviral (DAA) drugs, such as sofosbuvir. OBJECTIVES AND STUDY DESIGN: Here we evaluated in a routine practice setting, the treatment responses, tolerance and factors associated with SVR of a triple therapy with BOC or TVR, combined with pegylated interferon and ribavirin (PegIFN/RBV) in HIV/HCV co-infected patients, included in a large cohort of HIV/HCV coinfected patients (ANRS CO13-HEPAVIH). RESULTS: Among the 89 HIV/HCV coinfected patients treated, 65% of whom were previous non-responders to PegIFN/RBV therapy, 65%, 55% and 41% had at baseline genotype 1a, a high baseline HCV-RNA (≥800,000 IU/ml) and a cirrhosis, respectively. The SVR12 rate was 63% overall, 53% for BOC-based regimen and 66% for TVR-based regimen. In multivariate analysis, two factors were significantly associated with HCV SVR: HCV viral load <800,000 IU/mL at treatment initiation versus ≥800,000 IU/mL (OR 4.403, 95% CI 1.29-15.04; p=0.018) and virological response at W4 (HCV-RNA undetectable after 4 weeks of triple therapy) (OR 3.35, 95% CI 1.07-10.48; p=0.038). CONCLUSIONS: Overall SVR12 was 63% and our results suggest that HIV/HCV coinfected patients with low HCV viral load (<800,000 IU/mL) and undetectable HCV-RNA after 4 weeks of triple therapy with TVR or BOC-based regimen have a higher probability of treatment success.

Comparison of transient elastography (FibroScan), FibroTest, APRI and two algorithms combining these non-invasive tests for liver fibrosis staging in HIV/HCV coinfected patients: ANRS CO13 HEPAVIH and FIBROSTIC collaboration.

OBJECTIVES: Combining noninvasive tests increases diagnostic accuracy for staging liver fibrosis in hepatitis C virus (HCV)-infected patients, but this strategy remains to be validated in HIV/HCV coinfection. We compared the performances of transient elastography (TE), Fibrotest (FT), the aspartate aminotransferase-to-platelet ratio index (APRI) and two algorithms combining TE and FT (Castera) or APRI and FT (SAFE) in HIV/HCV coinfection. METHODS: One hundred and sixteen HIV/HCV-coinfected patients (64% male; median age 44 years) enrolled in two French multicentre studies (the HEPAVIH cohort and FIBROSTIC) for whom TE, FT and APRI data were available were included in the study. Diagnostic accuracies for significant fibrosis (METAVIR F ≥ 2) and cirrhosis (F4) were evaluated by measuring the area under the receiver-operating characteristic curve (AUROC) and calculating percentages of correctly classified (CC) patients, taking liver biopsy as a reference. RESULTS: For F ≥ 2, both TE and FT (AUROC = 0.87 and 0.85, respectively) had a better diagnostic performance than APRI (AUROC = 0.71; P < 0.005). Although the percentage of CC patients was significantly higher with Castera's algorithm than with SAFE (61.2% vs. 31.9%, respectively; P < 0.0001), this percentage was lower than that for TE (80.2%; P < 0.0001) or FT (73.3%; P < 0.0001) taken separately. For F4, TE (AUROC = 0.92) had a better performance than FT (AUROC = 0.78; P = 0.005) or APRI (AUROC = 0.73; P = 0.025). Although the percentage of CC patients was significantly higher with the SAFE algorithm than with Castera's (76.7% vs. 68.1%, respectively; P < 0.050), it was still lower than that for TE (85.3%; P < 0.033). CONCLUSIONS: In HIV/HCV-coinfected patients, TE and FT have a similar diagnostic accuracy for significant fibrosis, whereas for cirrhosis TE has the best accuracy. The use of the SAFE and Castera algorithms does not seem to improve diagnostic performance.

Factors associated with guideline-based hepatitis C virus (HCV) treatment initiation in HIV/HCV-coinfected patients: role of comorbidities and physicians' perceptions.

OBJECTIVES: Many HIV-infected patients with chronic hepatitis C virus (HCV) infection do not receive treatment for HCV infection, often because of contraindications or poor adherence to anti-HIV therapy. The aim of this study was to identify factors influencing guideline-based HCV treatment initiation in a large cohort of HIV/HCV-coinfected patients. METHODS: Between 2005 and 2011, 194 (40.5%) of 479 coinfected patients not previously treated for HCV infection started this treatment based on current recommendations, i.e. a Metavir score >F1 for liver fibrosis; HCV genotype 2 or 3 infection; or HCV genotype 1 or 4 infection and low HCV viral load (<800000 IU/mL), whatever the fibrosis score. Clinical and biological data were compared between patients who started HCV therapy during follow-up and those who did not. RESULTS: In multivariate analyses, good adherence to treatment for HIV infection, as judged by the patient's physician, was associated with HCV treatment initiation [odds ratio (OR) 2.37; 95% confidence interval (CI) 1.17-4.81; P=0.017], whereas patients with children (OR 0.53; 95% CI 0.30-0.91; P=0.022) and those with cardiovascular disease or respiratory distress (OR 0.10; 95% CI 0.01-0.78; P=0.03) were less likely to be treated. CONCLUSIONS: Adherence to treatment for HIV infection, as judged by the patient's physician, appears to have a major influence on the decision to begin treatment for HCV infection in coinfected patients. This calls for specific therapeutic education and adherence support in order to ensure timely anti-HCV therapy in this population.

Prevalence of immunity to hepatitis viruses A and B in a large cohort of HIV/HCV-coinfected patients, and factors associated with HAV and HBV vaccination.

UNLABELLED: Hepatitis A (HAV) and B (HBV) vaccination is strongly recommended for HIV-infected patients, especially those with hepatitis C coinfection. The aim of this study was to determine the prevalence of antibodies directed against HAV and HBV in a large cohort of HIV/HCV-coinfected patients, and to identify factors associated with HAV and HBV vaccination. PATIENTS AND METHODS: We studied 1175 HIV/HCV-coinfected patients enrolled in the ANRS CO13 HEPAVIH cohort, whose HAV and HBV serostatus was known. RESULTS: 1056 patients (89.9%) have been tested for anti-HBc IgG, anti-HBs, and HbsAg. Only 10.9% of patients had received HBV vaccination and 70% of the patients with no HBV immunity (231/265) had never received HBV vaccination. In multivariate analysis, male sex (OR 2.0. 95% CI 1.1-3.8; p=0.02), a higher level of school education (OR 2.5, 95% CI 1.3-4.5; p=0.003), a higher CD4 cell nadir (OR 1.05, 95% CI 1.009-1.103; p=0.018) and no cirrhosis (OR 2.7, 95% CI 1.2-6.4; p=0.02) were associated with HBV vaccination. Only 368 patients (31.3%) were tested for immunity to HAV. Despite a frequent lack of HAV immunity (48.3%), a low rate of HAV vaccination (6%) was observed. In multivariate analysis, a higher level of school education (OR 3.6, 95% CI 1.03-12.4; p=0.045) was the only factor associated with HAV vaccination. HAV screening rates and HAV and HBV vaccination rates were low in this population of HIV/HCV-coinfected patients. The benefits of routine HAV and HBV screening, vaccination and post-vaccination testing should be emphasized.

Impact of HAART exposure and associated lipodystrophy on advanced liver fibrosis in HIV/HCV-coinfected patients.

The impact of antiretroviral drug exposure and associated lipodystrophy and/or insulin resistance (IR) on advanced liver fibrosis in HIV/HCV-coinfected patients is not fully documented. We determined the prevalence of advanced liver fibrosis (defined by hepatic stiffness ≥9.5 kPa) and associated factors, focusing on the impact of highly active antiretroviral therapy and its major adverse effects (lipodystrophy and IR), in 671 HIV/HCV-coinfected patients included in the ANRS CO13 HEPAVIH cohort. One hundred ninety patients (28.3%) had advanced liver fibrosis. In univariate analysis, advanced liver fibrosis was significantly associated with male sex, higher body mass index, HCV infection through intravenous drug use, a lower absolute CD4 cell count, a longer history of antiretroviral treatment, longer durations of protease inhibitors, non-nucleoside reverse transcriptase inhibitors and NRTI exposure, lipodystrophy, diabetes, and a high homeostasis model assessment method (HOMA) value. The only antiretroviral drugs associated with advanced liver fibrosis were efavirenz, stavudine and didanosine. In multivariate analysis, male sex (OR 2.0, 95% CI 1.1-3.5; P = 0.018), HCV infection through intravenous drug use (OR 2.0, 95% CI 1.1-3.6; P = 0.018), lipodystrophy (OR 2.0, 95% CI 1.2-3.3; P = 0.01), median didanosine exposure longer than 5 months (OR 1.7, 95% CI 1.0-2.8; P = 0.04) and a high HOMA value (OR 1.1, 95% CI 1.0-1.2; P = 0.005) remained significantly associated with advanced liver fibrosis. Mitochondrial toxicity and IR thus appear to play a key role in liver damage associated with HIV/HCV-coinfection, and this should be taken into account when selecting and optimizing antiretroviral therapy. Antiretroviral drugs with strong mitochondrial toxicity (e.g. didanosine) or a major effect on glucose metabolism should be avoided.

Role of treatment for depressive symptoms in relieving the impact of fatigue in HIV-HCV co-infected patients: ANRS Co13 Hepavih, France, 2006-2008.

Fatigue is a major component of quality of life (QOL) and is associated with depression in HIV-HCV co-infected individuals. We investigated whether treating depressive symptoms (DS) could mitigate the impact of fatigue on daily functioning in co-infected patients, even those at an advanced stage of disease. The analysis was conducted on enrollment data of 328 HIV-HCV co-infected patients recruited in the French nationwide ANRS CO 13 HEPAVIH cohort. Data collection was based on medical records and self-administered questionnaires which included items on socio-behavioural data, the fatigue impact scale (FIS) in three domains (cognitive, physical and social functioning), depressive symptoms (CES-D classification) and use of treatments for depressive symptoms (TDS). After multiple adjustment for gender and unemployment, CD4 cell count <200 per mm(3) was associated with a negative impact of fatigue on the physical functioning dimension (P = 0.002). A higher number of symptoms causing discomfort significantly predicted a higher impact of fatigue on all three dimensions (P < 0.001). This was also true for patients with DS receiving TDS when compared with those with no DS but receiving TDS. A significant decreasing linear trend (P < 0.001) of the impact of fatigue was found across the categories 'DS/TDS', 'DS/no TDS', 'no DS/TDS' and 'no DS/no TDS'. Despite limitations related to the cross-sectional nature of this study, our results suggest that routine screening and treatment for DS can reduce the impact of fatigue on the daily functioning of HIV-HCV co-infected patients and relieve the burden of their dual infection.

Hepatic steatosis in HIV-HCV coinfected patients in France: comparison with HCV monoinfected patients matched for body mass index and HCV genotype.

BACKGROUND: Significance of steatosis in HIV-HCV coinfection remains controversial. AIM: To compare the prevalence and predictors of hepatic steatosis between HIV-HCV and HCV patients matched for steatosis known determinants. METHODS: A total of 564 HCV-naive patients undergoing liver biopsy were studied: 137 with HIV-HCV coinfection and 427 with HCV monoinfection, among whom 137 were matched for age, gender, body mass index and HCV genotype. RESULTS: Steatosis of any grade (67.1% vs. 41.6%, P < 0.0001), mixed steatosis (55.4% vs. 21.1%, P < 0.0001), severe histological activity (A2-A3: 78.1% vs. 55.5%, P < 0.0001) and severe fibrosis (F3-F4: 33.1% vs. 15.3%, P < 0.0001) were significantly more common in coinfected than in matched monoinfected patients. In multivariate analysis, steatosis was associated only with severe histological activity [odds ratio (OR): 3.1 (95% CI: 1.3-7.1)] in coinfected patients and with elevated body mass index [OR; 1.3 (1.1-1.5)], HCV genotype 3 [OR: 5.6 (2.3-13.9)], severe histological activity [OR: 3.1 (1.3-7.3)] and severe fibrosis [OR: 4.7 (1.3-17.3)] in monoinfected patients. CONCLUSIONS: Steatosis is significantly more common and severe in HIV-HCV coinfected than in HCV monoinfected French patients, even after matching for body mass index and HCV genotype. Steatosis is associated only with severe histological activity in coinfected patients and with previously reported factors in monoinfected patients, thus suggesting different underlying mechanisms.