RESUMO
The focus of this case study is the delayed diagnosis of a perinatal HIV transmission, which was identified when the infant reached 4 months of age, and the social conditions and structural determinants that contributed to the increased transmission risk. Despite adhering to the diagnostic testing protocols and neonatal antiretroviral (ARV) guidelines of the New York State Department of Health, this transmission still occurred. This transmission event prompted strategies to address criminalization of substance use during pregnancy and a reevaluation of the HIV testing and treatment protocols, including the timing of testing. Obtaining a diagnostic specimen at birth before initiating prophylactic or presumptive therapy, without causing delays in therapy, and incorporating HIV-1 DNA or RNA testing 2 to 6 weeks after discontinuing ARV therapy might have facilitated earlier detection and a quicker resumption of ARV therapy for this high-risk infant. Subsequently, the New York State HIV perinatal testing guidelines were updated. These changes included the recommendation to obtain a diagnostic specimen at birth before initiating ARV medications, whenever feasible, without causing delays in ARV initiation. Additionally, an extra virologic diagnostic test is recommended at 2 to 6 weeks after discontinuing ARVs for infants at high risk of perinatal HIV transmission, especially those with possible DNA or RNA suppression due to ARV prophylaxis or presumptive HIV therapy.
Assuntos
Infecções por HIV , Transmissão Vertical de Doenças Infecciosas , Humanos , Infecções por HIV/transmissão , Infecções por HIV/tratamento farmacológico , Infecções por HIV/diagnóstico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Feminino , Gravidez , New York/epidemiologia , Recém-Nascido , Lactente , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/diagnósticoRESUMO
High prevalences of HIV and other sexually transmitted infections (STIs) have been reported in the current global monkeypox outbreak, which has affected primarily gay, bisexual, and other men who have sex with men (MSM) (1-5). In previous monkeypox outbreaks in Nigeria, concurrent HIV infection was associated with poor monkeypox clinical outcomes (6,7). Monkeypox, HIV, and STI surveillance data from eight U.S. jurisdictions* were matched and analyzed to examine HIV and STI diagnoses among persons with monkeypox and assess differences in monkeypox clinical features according to HIV infection status. Among 1,969 persons with monkeypox during May 17-July 22, 2022, HIV prevalence was 38%, and 41% had received a diagnosis of one or more other reportable STIs in the preceding year. Among persons with monkeypox and diagnosed HIV infection, 94% had received HIV care in the preceding year, and 82% had an HIV viral load of <200 copies/mL, indicating HIV viral suppression. Compared with persons without HIV infection, a higher proportion of persons with HIV infection were hospitalized (8% versus 3%). Persons with HIV infection or STIs are disproportionately represented among persons with monkeypox. It is important that public health officials leverage systems for delivering HIV and STI care and prevention to reduce monkeypox incidence in this population. Consideration should be given to prioritizing persons with HIV infection and STIs for vaccination against monkeypox. HIV and STI screening and other recommended preventive care should be routinely offered to persons evaluated for monkeypox, with linkage to HIV care or HIV preexposure prophylaxis (PrEP) as appropriate.
Assuntos
Infecções por HIV , Mpox , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Animais , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Mpox/epidemiologia , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controleRESUMO
The "Undetectable = Untransmittable" campaign indicates that persons living with Human Immunodeficiency Virus (HIV) who maintain a suppressed viral load cannot sexually transmit the virus. However, there is little knowledge of the percent of individuals at a population level who sustain viral suppression long term. The aims of this study were to: (1) establish a baseline of persons living with diagnosed HIV who resided in New York and had consecutive suppressed viral load tests; (2) describe the risk of virologic failure among those who were consecutively suppressed; and (3) gain an understanding of the length of time between consecutive viral suppression to virologic failure. A total of 102,339 New Yorkers aged 13-90 years were living with diagnosed HIV at the beginning of 2012; 47.9% were consecutively suppressed (last two HIV viral load test results from 2010-2011 that were < 420 days apart and < 200 copies/mL). Of consecutively suppressed individuals, 54.3% maintained viral suppression for the entire study period and 33.6% experienced virologic failure during the study period. Among persons who experienced virologic failure, 82.6% did so six or more months after being consecutively suppressed. Our findings support the need for ongoing viral load monitoring, adherence support, and ongoing risk reduction messaging to prevent forward HIV transmission.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Fármacos Anti-HIV/uso terapêutico , Testes Diagnósticos de Rotina , HIV , Infecções por HIV/tratamento farmacológico , Humanos , New York , Carga ViralRESUMO
As part of the System Linkages and Access to Care Initiative, 12 HIV service delivery organizations in New York implemented one of the following three interventions to improve linkage to and retention in HIV care at their site: Peer Support, Appointment Procedures, and Anti-Retroviral Treatment and Access to Services. Aggregate process measure data describing intervention delivery, in conjunction with qualitative findings to help explain barriers and facilitators to achieving full implementation were examined. Process data from the interventions showed shortcomings in the percentage of eligible patients who went on to be enrolled, and the number of enrollees who ultimately received the components of the interventions. Factors identified in qualitative interviews that facilitated implementation and intervention delivery included: concerted buy-in and coordination of staff, building upon existing infrastructure including ensuring sufficient staff capacity, and allowing adaptability of certain parts of the intervention to better fit patient needs and clinical settings.
Assuntos
Continuidade da Assistência ao Paciente/organização & administração , Atenção à Saúde/organização & administração , Infecções por HIV/terapia , Acessibilidade aos Serviços de Saúde/organização & administração , Agendamento de Consultas , Infecções por HIV/epidemiologia , Humanos , Armazenamento e Recuperação da Informação , New York , Pesquisa QualitativaRESUMO
Existing data dissemination structures primarily rely on top-down approaches. Unless designed with the end user in mind, this may impair data-driven clinical improvements to Human Immunodeficiency Virus (HIV) prevention and care. In this study, we implemented a data visualization activity to create region-specific data presentations collaboratively with HIV providers, consumers of HIV care, and New York State (NYS) Department of Health AIDS Institute staff for use in local HIV care decision-making. Data from the NYS HIV Surveillance Registry (2009-2013) and HIV care facilities (2010-2015) participating in a Health Resources and Services Administration (HRSA) Systems Linkages and Access to Care project were used. Each data package incorporated visuals for: linkage to HIV care, retention in care and HIV viral suppression. End-users were vocal about their data needs and their capacity to interpret public health data. This experience suggests that data dissemination strategies should incorporate input from the end user to improve comprehension and optimize HIV care.
Assuntos
Participação da Comunidade/estatística & dados numéricos , Atenção à Saúde/organização & administração , Infecções por HIV/epidemiologia , Vigilância da População/métodos , Saúde Pública , Infecções por HIV/prevenção & controle , Humanos , Armazenamento e Recuperação da Informação , New York/epidemiologia , Avaliação de Programas e Projetos de Saúde , Pesquisa QualitativaRESUMO
Description: New York State Department of Health (NYSDOH) recommends that all pregnant patients receive human immunodeficiency virus (HIV) screening during pregnancy. This study assessed the prevalence of repeat prenatal HIV testing and factors associated with receipt of the recommended tests. Methods: Data from the NYSDOH newborn screening program were used to randomly select pregnant persons without HIV who delivered a liveborn infant in 2017. Receipt of repeat testing was defined as an initial HIV test in the first or second trimesters and the final in the third trimester (relaxed); or an initial test in the first trimester and the final in the third trimester (strict). Relative risks (RRs) and 95% confidence intervals were calculated in bivariate analyses. Adjusted RRs were calculated to determine associations between demographic and clinical factors and receipt of repeat HIV testing. Results: The cohort included 2,225 individuals. Roughly one quarter (24%) received the recommended tests in the first or second and third trimesters and 17% received them in the first and third trimesters. Individuals who reported Hispanic or Asian race/ethnicities, had government-funded insurance, started prenatal care in the first trimester, delivered in New York City, or received prenatal hepatitis C virus screening were significantly more likely to receive repeat testing using either definition. Conclusions: Despite the benefits and cost-effectiveness, the prevalence of repeat prenatal HIV screening during the third trimester remains persistently low. Improved messaging and targeted education and resources to assist prenatal providers could reinforce the importance of repeat testing and reduce residual perinatal HIV transmission.
RESUMO
The 2022 global mpox outbreak created an opportunity to test the utility of molecular HIV surveillance (MHS) to identify high-risk transmission networks. Individuals diagnosed with mpox in New York State (NYS) outside New York City-[Rest of State (ROS)] were matched to the NYS HIV and sexually transmitted infection registries. The demographic characteristics of individuals diagnosed with mpox in ROS mirror national trends. HIV-mpox comorbid individuals were more likely to be included in HIV molecular clusters compared to persons living with diagnosed HIV in ROS overall, men who have sex with men (MSM) in ROS, and age-adjusted MSM (to match individuals with mpox diagnosis) in ROS. For the 3-year 0.5% clusters, which are used to define national priority clusters, the HIV-mpox comorbid individuals clustered 2.4 times more frequently than the age/risk-adjusted control group. This study supports the use of HIV MHS to identify populations for priority public health interventions.
Assuntos
Infecções por HIV , Mpox , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Infecções por HIV/prevenção & controle , Cidade de Nova Iorque/epidemiologia , Espécies Reativas de Oxigênio , Análise por Conglomerados , MorbidadeRESUMO
This article is an examination of MTCT of HIV through breastfeeding in a mother who seroconverted postnatally.
Assuntos
Aleitamento Materno/tendências , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , HIV-1/isolamento & purificação , Transmissão Vertical de Doenças Infecciosas , Período Pós-Parto/sangue , Adulto , Aleitamento Materno/efeitos adversos , Feminino , Infecções por HIV/etiologia , Humanos , Lactente , Recém-Nascido , GravidezRESUMO
This study confirms the safety of endovascular interventions for thrombosis of hemodialysis access in outpatient and office-based settings.Risk of death in the week after vascular access procedure was not associated with hemodialysis access type (fistula versus graft).
Assuntos
Derivação Arteriovenosa Cirúrgica , Trombose , Humanos , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Pacientes Ambulatoriais , Diálise Renal , Trombose/etiologiaRESUMO
Importance: New York State has been an epicenter for both the US coronavirus disease 2019 (COVID-19) and HIV/AIDS epidemics. Persons living with diagnosed HIV may be more prone to COVID-19 infection and severe outcomes, yet few studies have assessed this possibility at a population level. Objective: To evaluate the association between HIV diagnosis and COVID-19 diagnosis, hospitalization, and in-hospital death in New York State. Design, Setting, and Participants: This cohort study, conducted in New York State, including New York City, between March 1 and June 15, 2020, matched data from HIV surveillance, COVID-19 laboratory-confirmed diagnoses, and hospitalization databases to provide a full population-level comparison of COVID-19 outcomes between persons living with diagnosed HIV and persons living without diagnosed HIV. Exposures: Diagnosis of HIV infection through December 31, 2019. Main Outcomes and Measures: The main outcomes were COVID-19 diagnosis, hospitalization, and in-hospital death. COVID-19 diagnoses, hospitalizations, and in-hospital death rates comparing persons living with diagnosed HIV with persons living without dianosed HIV were computed, with unadjusted rate ratios and indirect standardized rate ratios (sRR), adjusting for sex, age, and region. Adjusted rate ratios (aRRs) for outcomes specific to persons living with diagnosed HIV were assessed by age, sex, region, race/ethnicity, transmission risk, and CD4+ T-cell count-defined HIV disease stage, using Poisson regression models. Results: A total of 2988 persons living with diagnosed HIV (2109 men [70.6%]; 2409 living in New York City [80.6%]; mean [SD] age, 54.0 [13.3] years) received a diagnosis of COVID-19. Of these persons living with diagnosed HIV, 896 were hospitalized and 207 died in the hospital through June 15, 2020. After standardization, persons living with diagnosed HIV and persons living without diagnosed HIV had similar diagnosis rates (sRR, 0.94 [95% CI, 0.91-0.97]), but persons living with diagnosed HIV were hospitalized more than persons living without diagnosed HIV, per population (sRR, 1.38 [95% CI, 1.29-1.47]) and among those diagnosed (sRR, 1.47 [95% CI, 1.37-1.56]). Elevated mortality among persons living with diagnosed HIV was observed per population (sRR, 1.23 [95% CI, 1.07-1.40]) and among those diagnosed (sRR, 1.30 [95% CI, 1.13-1.48]) but not among those hospitalized (sRR, 0.96 [95% CI, 0.83-1.09]). Among persons living with diagnosed HIV, non-Hispanic Black individuals (aRR, 1.59 [95% CI, 1.40-1.81]) and Hispanic individuals (aRR, 2.08 [95% CI, 1.83-2.37]) were more likely to receive a diagnosis of COVID-19 than White individuals, but they were not more likely to be hospitalized once they received a diagnosis or to die once hospitalized. Hospitalization risk increased with disease progression to HIV stage 2 (aRR, 1.29 [95% CI, 1.11-1.49]) and stage 3 (aRR, 1.69 [95% CI, 1.38-2.07]) relative to stage 1. Conclusions and Relevance: In this cohort study, persons living with diagnosed HIV experienced poorer COVID-related outcomes relative to persons living without diagnosed HIV; Previous HIV diagnosis was associated with higher rates of severe disease requiring hospitalization, and hospitalization risk increased with progression of HIV disease stage.
Assuntos
COVID-19/epidemiologia , Comorbidade , Infecções por HIV/epidemiologia , Mortalidade Hospitalar , Hospitalização , Hospitais , Pandemias , Adulto , Negro ou Afro-Americano , Idoso , COVID-19/complicações , Estudos de Coortes , Epidemias , Feminino , Infecções por HIV/complicações , Hispânico ou Latino , Humanos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Cidade de Nova Iorque/epidemiologia , SARS-CoV-2 , População BrancaRESUMO
OBJECTIVES: In 2014, the governor of New York announced the Ending the Epidemic (ETE) plan to reduce annual new HIV infections from 3000 to 750, achieve a first-ever decrease in HIV prevalence, and reduce AIDS progression by the end of 2020. The state health department undertook participatory simulation modeling to develop a baseline for comparing epidemic trends and feedback on ETE strategies. METHODS: A dynamic compartmental model projected the individual and combined effects of 3 ETE initiatives: enhanced linkage to and retention in HIV treatment, increased preexposure prophylaxis (PrEP) among men who have sex with men, and expanded housing assistance. Data inputs for model calibration and low-, medium-, and high-implementation scenarios (stakeholders' rollout predictions, and lower and upper bounds) came from surveillance and program data through 2014, the literature, and expert judgment. RESULTS: Without ETE (baseline scenario), new HIV infections would decline but remain >750, and HIV prevalence would continue to increase by 2020. Concurrently implementing the 3 programs would lower annual new HIV infections by 16.0%, 28.1%, and 45.7% compared with baseline in the low-, medium-, and high-implementation scenarios, respectively. In all concurrent implementation scenarios, although annual new HIV infections would remain >750, there would be fewer new HIV infections than deaths, yielding the first-ever decrease in HIV prevalence. PrEP and enhanced linkage and retention would confer the largest population-level changes. CONCLUSIONS: New York State will achieve 1 ETE benchmark under the most realistic (medium) implementation scenario. Findings facilitated framing of ETE goals and underscored the need to prioritize men who have sex with men and maintain ETE's multipronged approach, including other programs not modeled here.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Epidemias/prevenção & controle , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Simulação por Computador , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Acessibilidade aos Serviços de Saúde/organização & administração , Humanos , Masculino , Modelos Teóricos , New York , Cooperação do Paciente , Profilaxia Pré-Exposição/métodos , Prevalência , Avaliação de Programas e Projetos de SaúdeRESUMO
BACKGROUND: New York State (NYS) has been an epicenter for both COVID-19 and HIV/AIDS epidemics. Persons Living with diagnosed HIV (PLWDH) may be more prone to COVID-19 infection and severe outcomes, yet few population-based studies have assessed the extent to which PLWDH are diagnosed, hospitalized, and have died with COVID-19, relative to non-PLWDH. METHODS: NYS HIV surveillance, COVID-19 laboratory confirmed diagnoses, and hospitalization databases were matched. COVID-19 diagnoses, hospitalization, and in-hospital death rates comparing PLWDH to non-PLWDH were computed, with unadjusted rate ratios (RR) and indirect standardized RR (sRR), adjusting for sex, age, and region. Adjusted RR (aRR) for outcomes among PLWDH were assessed by age/CD4-defined HIV disease stage, and viral load suppression, using Poisson regression models. RESULTS: From March 1-June 7, 2020, PLWDH were more frequently diagnosed with COVID-19 than non-PLWDH in unadjusted (RR [95% confidence interval (CI)]: 1.43[1.38-1.48), 2,988 PLWDH], but not in adjusted comparisons (sRR [95% CI]: 0.94[0.91-0.97]). Per-population COVID-19 hospitalization was higher among PLWDH (RR [95% CI]: 2.61[2.45-2.79], sRR [95% CI]: 1.38[1.29-1.47], 896 PLWDH), as was in-hospital death (RR [95% CI]: 2.55[2.22-2.93], sRR [95%CI]: 1.23 [1.07-1.40], 207 PLWDH), albeit not among those hospitalized (sRR [95% CI]: 0.96[0.83-1.09]). Among PLWDH, hospitalization risk increased with disease progression from HIV Stage 1 to Stage 2 (aRR [95% CI]:1.27[1.09-1.47]) and Stage 3 (aRR [95% CI]: 1.54[1.24-1.91]), and for those virally unsuppressed (aRR [95% CI]: 1.54[1.24-1.91]). CONCLUSION: PLWDH experienced poorer COVID-related outcomes relative to non-PLWDH, with 1-in-522 PLWDH dying with COVID-19, seemingly driven by higher rates of severe disease requiring hospitalization.
RESUMO
Mother-to-child-transmission of HIV in the United States has been greatly reduced, with clear benefits for the child. However, little is known about factors that predict maternal loss to HIV care in the postpartum year. This retrospective cohort study included 980 HIV-positive women, diagnosed with HIV at least one year before pregnancy, who had a live birth during 2008-2010 in New York State. Women who did not meet the following criterion in the 12 months after the delivery-related hospital discharge were considered to be lost to HIV care: two or more laboratory tests (CD4 or HIV viral load), separated by at least 90 days. Adjusted relative risks (aRR) and 95% confidence intervals (CI) for predictors of postpartum loss to HIV care were identified with Poisson regression, solved using generalized estimating equations. Having an unsuppressed (>200 copies/mL) HIV viral load in the postpartum year was also evaluated. Overall, 24% of women were loss to HIV care during the postpartum year. Women with low participation in HIV care during preconception were more likely to be lost to HIV care during the postpartum year (aRR: 2.70; 95% CI: 2.09-3.49). In contrast, having a low birth weight infant was significantly associated with a decreased likelihood of loss to HIV care (aRR: 0.72; 95% CI: 0.53-0.98). While 75% of women were virally suppressed at the last viral load before delivery only 44% were continuously suppressed in the postpartum year; 12% had no viral load test reported in the postpartum year and 44% had at least one unsuppressed viral load test. Lack of engagement in preconception HIV-related health care predicts postpartum loss to HIV care for HIV-positive parturient women. Many women had poor viral control during the postpartum period, increasing the risk of disease progression and infectivity.
Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Continuidade da Assistência ao Paciente/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Nascido Vivo , Perda de Seguimento , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Antivirais/uso terapêutico , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Lactente , Período Pós-Parto , Gravidez , Estudos Retrospectivos , Carga ViralRESUMO
OBJECTIVE: To identify factors associated with continuity of care and human immunodeficiency virus (HIV) virologic suppression among postpartum women diagnosed with HIV during pregnancy in New York State. METHODS: This retrospective cohort study was conducted among 228 HIV-infected women diagnosed during pregnancy between 2008 and 2010. Initial receipt of HIV-related medical care (first CD4 or viral load test after diagnosis) was evaluated at 30 days after diagnosis and before delivery. Retention in care (2 or more CD4 or viral load tests, 90 days or greater apart) and virologic suppression (viral load 200 copies/mL or less) were evaluated in the 12 months after hospital discharge. RESULTS: Most women had their initial HIV-related care encounter within 30 days of diagnosis (74%) and before delivery (87%). Of these women, 70% were retained in the first year postpartum. Women waiting more than 30 days for their initial HIV-related care encounter were more likely diagnosed in the first (29%) compared with the third (11%) trimester and were of younger (younger than 25 years, 32%) compared with older (35 years or older, 13%) age. Loss to follow-up within the first year was significantly greater among women diagnosed in the third compared with the first trimester (adjusted relative risk 2.21, 95% confidence interval [CI] 1.41-3.45) and among women who had a cesarean compared with vaginal delivery (adjusted relative risk 1.76, 95% CI 1.07-2.91). Of the 178 women with one or more HIV viral load test in the first year postpartum, 58% had an unsuppressed viral load. CONCLUSION: Despite the high proportion retained in care, many women had poor postpartum virologic control. Robust strategies are needed to increase virologic suppression among newly diagnosed postpartum HIV-infected women.
Assuntos
Infecções por HIV , Cuidado Pós-Natal , Complicações Infecciosas na Gravidez , Carga Viral , Adulto , Fatores Etários , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Perda de Seguimento , New York/epidemiologia , Cuidado Pós-Natal/métodos , Cuidado Pós-Natal/organização & administração , Período Pós-Parto/sangue , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Carga Viral/métodos , Carga Viral/estatística & dados numéricosRESUMO
BACKGROUND: The New York State HIV testing law requires that patients aged 13-64 years be offered HIV testing in health care settings. We investigated the extent to which HIV testing was offered and accepted during the 24 months after law enactment. METHODS: We added local questions to the Behavioral Risk Factor Surveillance System (BRFSS) and the National HIV Behavioral Surveillance (NHBS) surveys asking respondents aged 18-64 years whether they were offered an HIV test in health care settings, and whether they had accepted testing. Statewide prevalence estimates of test offers and acceptance were obtained from a combined 2011-2012 BRFSS sample (N = 6,223). Local estimates for 2 high-risk populations were obtained from NHBS 2011 men who have sex with men (N = 329) and 2012 injection drug users (N = 188) samples. RESULTS: BRFSS data showed that 73% of New Yorkers received care in any health care setting in the past 12 months, of whom 25% were offered an HIV test. Sixty percent accepted the test when offered. The levels of test offer increased from 20% to 29% over time, whereas acceptance levels decreased from 68% to 53%. NHBS data showed that 81% of men who have sex with men received care, of whom 43% were offered an HIV test. Eighty-eight percent accepted the test when offered. Eighty-five percent of injection drug users received care, of whom 63% were offered an HIV test, and 63% accepted the test when offered. CONCLUSIONS: We found evidence of partial and increasing implementation of the HIV testing law. Importantly, these studies demonstrated New Yorkers' willingness to accept an offered HIV test as part of routine care in health care settings.