ABSTRACT
PURPOSE: Hepatitis C virus (HCV) cure after treatment with direct-acting antivirals (DAAs) can improve health-related quality of life (HRQoL). However, specific groups with chronic HCV may still exhibit worse post-cure HRQoL because of persisting severe liver fibrosis or social vulnerability factors (e.g. unhealthy alcohol use, living in poverty). We assessed the effect of such factors on longitudinal measures of HRQoL in chronic HCV patients. METHODS: ANRS CO22 HEPATHER is a prospective cohort of chronic HCV patients receiving DAAs, which included notably patients with social vulnerability factors, a population usually under-represented in clinical trials. Multivariable mixed-effects linear regression models helped identify factors associated with longitudinal measures of HRQoL (PROQOL-HCV scores). RESULTS: At enrolment, 52.4% of the 2740 participants were men, median age was 56 years [interquartile range 50-64], and 21.5% had severe liver fibrosis (FIB-4 > 3.25). Twenty-eight per cent reported current or past unhealthy alcohol use [> 2(3) alcohol units per day for women (men)], and 28.1% were living in poverty (standard of living under 1015/month per household consumption unit). At first PROQOL-HCV completion, 54.0% of patients were HCV-cured. After multivariable adjustment, people with current or past unhealthy alcohol use, individuals living in poverty, those with severe liver fibrosis, and women had worse HRQoL in the dimensions explored. Conversely, HCV cure was associated with better HRQoL. CONCLUSIONS: Specific socially vulnerable groups of patients with chronic HCV infection still experience impaired HRQoL, independently of HCV cure. Patient-centred interventions, including social support and referral for comorbidities, should be prioritized for them. Trial registration with ClinicalTrials.gov NCT01953458.
Subject(s)
Hepatitis C, Chronic , Hepatitis C , Male , Humans , Female , Middle Aged , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Hepacivirus , Prospective Studies , Quality of Life/psychology , Liver Cirrhosis , Hepatitis C/drug therapy , Hepatitis C/complicationsABSTRACT
Alcohol use is a leading risk factor for premature death and disability. To tackle this issue, more systematic and accurate screening for at-risk consumption is needed in healthcare systems, especially by general practitioners (GPs). We assessed the frequency of at-risk consumption screening by GPs in France. We also identified characteristics associated with more frequent screening and greater use of validated screening tools by these healthcare providers. A cross-sectional survey was conducted among a representative sample of French GPs. Multinomial logistic regressions were used to identify factors associated with more frequent screening and greater use of validated screening tools. Response rate was of 73%. Of the 2412 participants, 42.8% screened all their patients systematically and repeatedly, while 48.0% never used standardized tools to screen potentially at-risk patients. Among other characteristics, being aware of and using the "early identification and brief intervention" screening strategy, and feeling absolutely comfortable talking with patients about reducing or stopping their alcohol use, were both associated with more frequent screening and use of standardized tools. Our results on at-risk alcohol use screening highlight an improvement over data from previous studies. Nevertheless, better training of French GPs in good alcohol screening practices-specifically, increased screening frequency and greater use of standardized tools-may improve identification of at-risk patients.
Subject(s)
General Practice , General Practitioners , Humans , Cross-Sectional Studies , Alcohol Drinking/epidemiology , Alcohol Drinking/prevention & control , Primary Health Care/methodsABSTRACT
BACKGROUND: Many risk factors impact the health of hospital night workers, which can lead to physical and mental health disorders. During the recent period, night hospital workers have been particularly stressed. This study therefore aims to: (i) To document the prevalence of depression, anxiety, sleep disorders, and symptoms suggestive of post-traumatic stress disorder in night shift workers (NSHW) working in Parisian public hospitals after France's first COVID-19 wave ended; (ii) To estimate the effect of negative representations and perceptions of night shift work on these mental health outcomes. METHODS: An observational cross-sectional online survey of NSHW (June to September 2020) in 39 public hospitals in Paris, France. Standard scales were used to measure mental health outcomes. Weighted multinomial logistic regression models supported the identification of predictors of depression (score > 10 on the Hospital Anxiety and Depression Scale, HADS, for depression), anxiety (score > 10 on the HADS for anxiety), severe insomnia (score > 21 on the Insomnia Severity Index, ISI) and symptoms suggestive of post-traumatic stress disorder (score > 36 on the Impact of Event Scale-Revised, IES-R). RESULTS: The weighted prevalence rates [95% confidence interval] of depression, anxiety, severe insomnia, and symptoms of post-traumatic stress disorder were, respectively, 18.9% [16.5-21.2], 7.6% [6.0-9.1], 8.6% [6.9-10.2] and 11.7% [9.7-13.6]. After multiple adjustment, organizational changes in NSHW professional lives due to the COVID-19 pandemic (such as moving to another hospital department and modified schedules) and NSHW-perceived negative representations of night work were significantly associated with all studied mental health outcomes. CONCLUSION: Our findings confirm the importance of monitoring mental health and sleep quality among NSHW in Parisian public hospitals, even more during health crises. Multilevel interventions aiming at reducing negative representations and improving work organization are urgently needed to improve overall health of this frontline healthcare providers group.
Subject(s)
COVID-19 , Shift Work Schedule , Sleep Initiation and Maintenance Disorders , Humans , COVID-19/epidemiology , Mental Health , Sleep Initiation and Maintenance Disorders/epidemiology , Pandemics , Cross-Sectional Studies , Depression/epidemiology , Health Personnel/psychology , Anxiety/epidemiologyABSTRACT
BACKGROUND AND AIMS: Late presentation for care of hepatitis C virus (HCV) infection - defined as having severe liver fibrosis when first consulting a specialist for HCV care - increases morbidity and mortality. Identifying the socio-behavioural correlates of late presentation is essential to improve HCV strategies to optimize HCV cascade of care. We investigated clinical and socio-behavioural correlates of late presentation for care in HCV mono-infected individuals. METHODS: This study included chronic HCV mono-infected patients participating in the French national cohort ANRS CO22 HEPATHER, starting in 2012. The correlates of late presentation were estimated using a Heckman probit selection model, which takes into account the possible selection bias because of missing data in the outcome. RESULTS: Among the 9174 study patients, 1236 had available data on liver fibrosis stage at first presentation for HCV care. Of these, 591 (47.8%) were late presenters. In a multivariable analysis adjusted for age, sex and HCV genotype, having diabetes (adjusted coefficient [95% confidence interval]: 0.55 [0.30; 0.80]), current hazardous alcohol use (0.36 [0.03; 0.69]) and current abstinence but past hazardous alcohol use (0.42 [0.19; 0.64]) (vs. current abstinence and no past hazardous use) were all independently associated with late presentation for HCV care. CONCLUSIONS: As late presentation severely affects HCV cascade of care, our findings bring important new evidence about the need to promptly identify and target people with diabetes and/or past or current hazardous alcohol use for HCV screening and treatment within the wider context of the WHO goal to eliminate HCV by 2030.
Subject(s)
Diabetes Mellitus , HIV Infections , Hepatitis C, Chronic , Hepatitis C , Antiviral Agents/therapeutic use , Diabetes Mellitus/drug therapy , HIV Infections/complications , Hepacivirus/genetics , Hepatitis C/drug therapy , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Humans , Liver Cirrhosis/complicationsABSTRACT
BACKGROUND: Opioid agonist therapy (OAT) is associated with reduced injection, reduced HCV transmission, and more opportunities to initiate hepatitis C virus (HCV) treatment in people who use drugs (PWUD). We aimed to study the extent to which adherence to OAT was predictive of increased uptake of direct-acting antivirals (DAA) in PWUD with chronic HCV infection. METHODS: Using the French national healthcare system database, we targeted PWUD (i.e. with a history of OAT) who had chronic HCV infection and were eligible for DAA during 2014-2016. Adherence to OAT was computed as a time-varying variable expressing the proportion of days covered by OAT receipt, over any six-month interval before DAA receipt. We used a Cox proportional hazards model to estimate the association between adherence to OAT and the rate of DAA uptake after adjustment for age, sex, alcohol use disorder, socioeconomic status, and liver disease severity. RESULTS: Among the 22,615 persons included in the ANRS FANTASIO study, 3438 (15.2%) initiated DAA during the study period. After multivariable adjustment, adherence to OAT was associated with a higher rate of DAA initiation. However, this association was not linear, and only individuals on OAT for 20% or more of the time in the previous six-month period had a higher rate of DAA initiation (adjusted hazard ratio [95% confidence interval]: 1.28 [1.18-1.38]). Other variables associated with DAA initiation were male sex, older age, cirrhosis or liver cancer, and higher socioeconomic status. CONCLUSIONS: Adherence to OAT is a major predictor of DAA initiation in PWUD living with chronic HCV infection in France. Our results also suggest that even moderate adherence to OAT can facilitate DAA uptake. Adequate HCV training for OAT prescribers together with interventions to ensure adherence to OAT will help improve DAA initiation rates and reach HCV elimination goals.
Subject(s)
Hepatitis C, Chronic , Hepatitis C , Male , Humans , Female , Hepatitis C, Chronic/drug therapy , Antiviral Agents/therapeutic use , Analgesics, Opioid/therapeutic use , Hepatitis C/drug therapy , Hepatitis C/complications , Hepacivirus , Delivery of Health CareABSTRACT
There remains a substantial gap in our understandings of the life experiences of patients following HCV cure among HIV-HCV-co-infected people who inject drugs (PWID) and men who have sex with men (MSM), two key populations targeted for HCV elimination. We described the experiences and perspectives of HIV-positive PWID and MSM, HCV-cured following treatment with direct-acting antivirals (DAA). We used an exploratory sequential mixed approach using both qualitative data (semi-structured interviews with 27 PWID and 20 MSM) and quantitative data (self-administered questionnaires with 89 PWID) via the prospective ANRS CO13 HEPAVIH cohort. PWID reported improvements in physical health-related quality of life (HRQL) and self-reported symptoms following treatment, but no significant change in mental HRQL. During interviews, several MSM, more recently diagnosed with HCV, expressed less concern regarding HCV than HIV infection and interpreted improvements in their overall well-being after HCV cure to be more related to a closer connection with healthcare providers than with viral elimination. By contrast, PWID, particularly those previously exposed to interferon-based treatments, described major improvements in their physical HRQL. Both MSM and PWID reported improvements in cognitive or psychological wellbeing, and a majority of them reported some degree of concern over potential HCV reinfection. To conclude, though health benefits of HCV cure concern both groups, HIV-infected PWID and MSM may have different representations and experiences following DAA treatment, related to their history with HCV. They are thus likely to benefit from holistic, post-treatment follow-up care that is responsive to their evolving health and social contexts.
Subject(s)
HIV Infections , Hepatitis C, Chronic , Hepatitis C , Pharmaceutical Preparations , Sexual and Gender Minorities , Substance Abuse, Intravenous , Antiviral Agents/therapeutic use , HIV Infections/complications , HIV Infections/drug therapy , Hepatitis C/complications , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Homosexuality, Male , Humans , Male , Perception , Prospective Studies , Quality of Life , Substance Abuse, Intravenous/complications , Substance Abuse, Intravenous/drug therapySubject(s)
Cannabis , Coinfection , HIV Infections , Hepatitis C, Chronic , Hepatitis C , HIV , HIV Infections/complications , HIV Infections/drug therapy , Hepacivirus/genetics , Hepatitis C/complications , Hepatitis C/drug therapy , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Humans , Plasma , RNASubject(s)
Antiviral Agents , Coinfection , HIV Infections , Hepatitis C, Chronic , Hepatitis C , Antiviral Agents/therapeutic use , Coinfection/drug therapy , HIV Infections/complications , HIV Infections/drug therapy , Hepatitis C/complications , Hepatitis C/drug therapy , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Humans , Patient Reported Outcome MeasuresABSTRACT
INTRODUCTION: Cannabidiol (CBD) is a non-intoxicating cannabis compound found in diverse commercial products worldwide. However, its use may not be fully harmless. Accordingly, it is important to document the prevalence of CBD use and user characteristics in the general population. METHODS: We conducted a nationwide survey from a random sample of adults living in France using computer-assisted telephone interviews between 2 March and 9 July 2022. We estimated the prevalence of CBD awareness and CBD use, and explored the different routes of administration. We also performed logistic regression models to identify factors associated with past-year CBD use. RESULTS: Based on data from 3229 participants, we estimated that 71.0% (95% confidence interval) (69.0-73.0) of the French adult population had heard of CBD, and 10.1% (8.7-11.4) had used it in the previous year. Past-year CBD use was associated with younger age, a higher educational level, not living in a middle-sized urban unit, tobacco consumption and e-cigarette use. The most common route of administration was smoking (56.1%). DISCUSSION AND CONCLUSION: Past-year CBD use prevalence in France appeared to be as high as that for cannabis. Proper prevention, regulation and control of CBD products is necessary to ensure that people have access to safe and high-quality products. Reliable information on CBD should be sought and disseminated, especially regarding the harms associated with smoking the compound.
Subject(s)
Cannabidiol , Humans , Cannabidiol/administration & dosage , France/epidemiology , Adult , Male , Female , Middle Aged , Young Adult , Prevalence , Adolescent , Aged , Surveys and QuestionnairesABSTRACT
INTRODUCTION: The risk of mortality in people with a history of injection drug use (PHID) is high, as is the prevalence of hepatitis C virus (HCV) infection. Although direct-acting antivirals (DAA) are effective in this population in terms of sustained virological response, it is not known whether PHID benefit as much as people with no history of injection drug use from DAA-related HCV cure in terms of reduced all-cause mortality. METHODS: Using Cox proportional hazards models based on the ANRS CO22 Hepather cohort data (n = 9735), we identified factors associated with all-cause mortality among HCV-infected people. We tested for interaction effects between drug injection status, HCV cure and other explanatory variables. RESULTS: DAA-related HCV cure was associated with a 66% (adjusted hazard ratio [95% confidence interval]: 0.34 [0.29-0.39]) lower risk of all-cause mortality, irrespective of drug injection status. Detrimental effects of unhealthy alcohol use on mortality were identified in PHID only. DISCUSSION AND CONCLUSIONS: DAA-related HCV cure led to comparable benefits in terms of reduced mortality in PHID and people with no history of injection drug use. Policies and strategies to enhance DAA uptake among PHID are needed to lower mortality in this population. Clinical trial registration details: ClinicalTrials.gov: NCT01953458.
Subject(s)
Hepatitis C, Chronic , Hepatitis C , Humans , Antiviral Agents/therapeutic use , Hepacivirus , Hepatitis C, Chronic/drug therapy , Hepatitis C/epidemiology , Alcohol DrinkingABSTRACT
Background & Aims: A growing literature shows an improvement of chronic hepatitis C virus (HCV)-related depression after successful treatment with direct-acting antivirals. However, depression after HCV cure remains insufficiently documented in people living with HIV (PLWH) and HCV, a population with specific mental health challenges. This study aimed to (i) document the prevalence of moderate-to-severe depression (PHQ-9 score ≥10) across different age classes in HCV-cured PLWH; (ii) identify associated socio-behavioral correlates. Methods: Descriptive analyses were performed on data collected during a cross-sectional survey (February 2018 - May 2019) nested in a prospective, multicenter cohort of individuals living with HIV and HCV (ANRS CO13 HEPAVIH). Socio-behavioral correlates of moderate-to-severe depression were identified using logistic regression. Results: Among the 398 HCV-cured individuals in the study sample (median age [IQR]: 56 [53-59] years; 73.1% men), 23.9% presented with moderate-to-severe depression (PHQ-9 score ≥10). Depressive symptom prevalence rates were as follows: anhedonia: 52.3%; feeling 'down' or feelings of hopelessness: 48.3%; sleeping problems: 65.7%; lack of energy: 70.3%; eating disorders: 51.2%; lack of self-esteem: 34.3%; difficulty concentrating: 34.9%; sluggishness (in movement and voice) or restlessness: 24.6%; suicidal ideation: 17.1%. No significant difference was detected across age classes. Female sex, unhealthy alcohol use, sedentary lifestyle, and unhealthy eating behaviors were associated with increased odds of moderate-to-severe depression. Conclusions: Depressive symptoms were common in this sample of HCV-cured PLWH. Unlike findings for the French general population, the prevalence of depression did not decrease with age class. Mental health remains a key issue for HIV-HCV-coinfected individuals, even after HCV cure, especially in women and in individuals with unhealthy behaviors. Lay summary: Despite potential improvements in mental health after successful treatment with direct-acting antivirals, many people living with HIV (PLWH) and hepatitis C virus (HCV) - even in older age classes - still face depressive symptoms after HCV cure. In this population, women and people reporting unhealthy alcohol use, sedentary lifestyle, or unhealthy eating behaviors are more prone to report depressive symptoms after HCV cure. Mental health and lifestyle-related issues should be integrated in a global care model for PLWH living with or having a history of hepatitis C.
ABSTRACT
INTRODUCTION: Alcohol use disorder (AUD) is associated with a significant disease burden in France, where alcohol use is deeply rooted in culture. However, the treatment gap is large because of several barriers, including stigmatisation and drinkers' apprehension about total abstinence. However, standardised and evidence-based interventions based on controlled-drinking for people with AUD are lacking. We aimed to assess the effectiveness of a novel community-based French therapeutic patient education (TPE) program for people with AUD named Choizitaconso. METHODS: A before-after non-randomised quasi-experimental study, named ETHER, was designed and implemented with people living with AUD, over a period of 6 months. The primary outcome was percentage change in the number of alcohol-related harms experienced. Secondary outcomes were percentage changes in psycho-social patient-reported and community-validated outcomes. Participants in the intervention group (n = 34) benefited from the 10-week TPE program Choizitaconso, while the comparison group (n = 58) received standard care. The Kruskall-Wallis and chi-squared or Fisher's exact tests were used to compare before-after changes in variables in both groups. Linear regression models were used to test for the effect of study group on each outcome and to test for the effect of alcohol consumption as a confounder. RESULTS: At 6 months, all outcomes but one either remained stable or numerically improved in both groups. Internalised stigma significantly improved in the intervention group (p = 0.026) but not in the comparison group (p = 0.207), with a significant group effect (p = 0.014). DISCUSSION AND CONCLUSIONS: This study demonstrates the effectiveness of the Choizitaconso TPE program on community-validated outcomes, especially internalised stigma.
Subject(s)
Alcoholism , Humans , Alcoholism/therapy , Alcohol Drinking/therapy , FranceABSTRACT
Background: Although cannabis use is common in France, it is still criminalized. Cannabidiol (CBD) products, including CBD-rich cannabis, are legally available. Although previous results suggested that CBD may have benefits for people with cannabis use disorder, there is a lack of data on cannabis users who use CBD to reduce their cannabis consumption. We aimed to identify (i) correlates of this motive, and (ii) factors associated with successful attempts to reduce cannabis use. Methods: A cross-sectional online survey among French-speaking CBD and cannabis users was conducted. Logistic regressions were performed to identify correlates of using CBD to reduce cannabis consumption and correlates of reporting a large reduction. Results: Eleven percent (n = 105) of our study sample reported they primarily used CBD to reduce cannabis consumption. Associated factors included smoking tobacco cigarettes (adjusted odds ratio (aOR) [95% confidence interval (CI)] 2.17 [1.3-3.62], p = 0.003) and drinking alcohol (aOR [95%CI] 1.8 [1.02-3.18], p = 0.042). Of these 105, 83% used CBD-rich cannabis to smoke, and 58.7% reported a large reduction in cannabis consumption. This large reduction was associated with non-daily cannabis use (aOR [95%CI] 7.14 [2.4-20.0], p < 0.001) and daily CBD use (aOR [95%CI] 5.87 [2.09-16.47], p = 0.001). A reduction in cannabis withdrawal symptoms thanks to CBD use was the most-cited effect at play in self-observed cannabis reduction. Conclusions: Cannabis use reduction is a reported motive for CBD use-especially CBD-rich cannabis to smoke-in France. More studies are needed to explore practices associated with this motive and to accurately assess CBD effectiveness.
ABSTRACT
OBJECTIVE: Documenting the perceptions and experiences of frontline healthcare workers during a sanitary crisis is key to reinforce healthcare systems. We identify the determinants of quality of working life (QWL) among night-shift healthcare workers (NSHW) in Paris public hospitals shortly after the first-wave of the COVID-19 pandemic. METHODS: The ALADDIN cross-sectional online survey (15 June to 15 September 2020) collected QWL, socio-economic, behavioral, and work-related information among 1,387 NSHW in the 39 hospitals of the Assistance Publique-Hôpitaux de Paris (AP-HP). Data were weighted (margin calibration) to be representative of the entire population of 12,000 AP-HP hospitals' NSHW regarding sex, age, and professional category. Linear regression was used to identify correlates of QWL (WRQoL scale). RESULTS: New night position during the COVID pandemic, difficulties in getting screened for COVID, and considering protective measures inadequate were associated with poorer QWL, after adjustment for socio-economic characteristics, professional category, perceived health, physical activity, and history of harassment at work. Under-estimation of night-shift work by day-shift colleagues, reporting night work as a source of tension with friends, or feeling more irritable since working at night also impaired QWL. By contrast, satisfaction regarding COVID information received from the employer, and feeling valued by the general population during the pandemic improved QWL. CONCLUSIONS: Insufficient access to screening, information, and protective measures impaired QWL of NSHW after the first wave of COVID-19 in Paris public hospitals. Social and professional recognition of night-shift work were the key determinants of QWL in this population.
Subject(s)
COVID-19 , Quality of Life , COVID-19/epidemiology , Cross-Sectional Studies , Delivery of Health Care , Health Personnel , Hospitals, Public , Humans , PandemicsABSTRACT
OBJECTIVES: This study aimed to estimate the prevalence of psychoactive substance (PAS) use in night-shift healthcare workers (NSHW) during France's first COVID-19 wave (March-May 2020). DESIGN: Observational cross-sectional online survey. SETTING: 39 public hospitals in the Assitance Publique des Hôpitaux de Paris (AP-HP) network in the Parisian area. PARTICIPANTS: A total of 1238 nurses, assistant nurses, X-ray technicians, managers, lab technicians, midwives and childcare assistants working at night or alternating between days and nights answered the questionnaire. INTERVENTION: Online survey. OUTCOME MEASURES: PAS use prevalence after weighting data for sex, age and profession using calibration on margins, in order to be representative of all AP-HP NSHW. We used the Fagerström scale and the Alcohol Use Disorders Identification Test Concise to assess PAS use. RESULTS: The weighted estimated prevalences of daily smoking, alcohol drinking and tranquilliser use in participating NSHW were 21.4, 1.3 and 2.4%, respectively. Twelve per cent (11.7%) of our study sample used opioids. During the first COVID-19 wave, PAS use remained stable except for tobacco use, with 8.6% of participants reporting an increase. Previous 3-month prevalences of tranquilliser and opioid use were significantly higher than in the general population. CONCLUSION: Daily smoking (especially in younger men) and tranquilliser and opioid use were highly prevalent in NSHW in the AP-HP network during France's first COVID-19 wave. Specific interventions for quitting smoking and addressing determinants of tranquilliser and opioid use in NSHW need to be developed and evaluated to improve quality of life in these essential, underdiagnosed and undertreated health personnel.
Subject(s)
Alcoholism , COVID-19 , COVID-19/epidemiology , Cross-Sectional Studies , Health Personnel , Hospitals, Public , Humans , Male , Pandemics , Quality of Life , SARS-CoV-2ABSTRACT
BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection is associated with the onset of metabolic disorders which constitute risk factors for liver disease progression. Their impact may persist after the HCV infection has been cured. Cannabis use is associated with a lower risk of obesity and diabetes in both general and HCV populations. The associations between cannabis use and both dyslipidemia and hypertension have not yet been studied in persons with chronic HCV infection. METHODS: Using cross-sectional data from the French ANRS CO22 Hepather cohort, we used regression models to test for an inverse relationship between cannabis use and (i) dyslipidemia, (ii) hypertension, and (iii) the total number of metabolic disorders. RESULTS: Among the 6364 participants in the study population, both former and current cannabis use were associated with a lower risk of hypertension and fewer metabolic disorders. These results were independent of central obesity. Cannabis use was not associated with dyslipidemia. CONCLUSIONS: In people chronically infected with HCV, cannabis use was associated with a lower risk of hypertension and a lower number of metabolic disorders. Post-HCV cure studies are needed to confirm these findings using longitudinal data and to test whether they translate into reduced mortality in this population.