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BACKGROUND: Anemia is common and associated with increased morbidity among people with HIV (PWH). Classification of anemia using the mean corpuscular volume (MCV) can help investigate the underlying causative factors of anemia. We characterize anemia using MCV among PWH receiving antiretroviral therapy (ART), and identify the risk factors for normocytic, macrocytic, and microcytic anemias. METHODS: Including PWH with anemia (hemoglobin measure < 12.9 g/dL among men and < 11.9 g/dL among women) in the NA-ACCORD from 01/01/2007 to 12/31/2017, we estimated the annual distribution of normocytic (80-100 femtolitre (fL)), macrocytic (> 100 fL) or microcytic (< 80 fL) anemia based on the lowest hemoglobin within each year. Poisson regression models with robust variance and general estimating equations were used to estimate crude and adjusted prevalence ratios and 95% confidence intervals for risk factors for macrocytic (vs. normocytic) and microcytic (vs. normocytic) anemia stratified by sex. RESULTS: Among 37,984 hemoglobin measurements that identified anemia in 14,590 PWH, 27,909 (74%) were normocytic, 4257 (11%) were microcytic, and 5818 (15%) were macrocytic. Of the anemic PWH included over the study period, 1910 (13%) experienced at least one measure of microcytic anemia and 3208 (22%) at least one measure of macrocytic anemia. Normocytic anemia was most common among both males and females, followed by microcytic among females and macrocytic among males. Over time, the proportion of anemic PWH who have macrocytosis decreased while microcytosis increased. Macrocytic (vs. normocytic) anemia is associated with increasing age and comorbidities. With increasing age, microcytic anemia decreased among females but not males. A greater proportion of PWH with normocytic anemia had CD4 counts ≤ 200 cells/mm3 and had recently initiated ART. CONCLUSION: In anemic PWH, normocytic anemia was most common. Over time macrocytic anemia decreased, and microcytic anemia increased irrespective of sex. Normocytic anemia is often due to chronic disease and may explain the greater risk for normocytic anemia among those with lower CD4 counts or recent ART initiation. Identified risk factors for type-specific anemias including sex, age, comorbidities, and HIV factors, can help inform targeted investigation into the underlying causes.
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Anemia , Índices de Eritrocitos , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/sangre , Masculino , Femenino , Anemia/epidemiología , Anemia/sangre , Adulto , Persona de Mediana Edad , Factores de Riesgo , América del Norte/epidemiología , Prevalencia , Hemoglobinas/análisis , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4RESUMEN
Background: Thirty-day hospital readmission measures quality of care, but there are limited data among people with HIV (PWH) and people without HIV (PWoH) in the era of universal recommendation for antiretroviral therapy. We descriptively compared 30-day all-cause, unplanned readmission risk between PWH and PWoH. Methods: A retrospective cohort study was conducted using the 2019 Nationwide Readmissions Database (2019/01/01-2019/12/31), an all-payer database that represents all US hospitalizations. Index (initial) admissions and readmissions were determined using US Centers for Medicare & Medicaid Services definitions. Crude and age-adjusted risk ratios (aRR) comparing the 30-day all-cause, unplanned readmission risk between PWH to PWoH were estimated using random effect logistic regressions and predicted marginal estimates. Survey weights were applied to all analyses. Findings: We included 24,338,782 index admissions from 18,240,176 individuals. The median age was 52(IQR = 40-60) years for PWH and 61(IQR = 38-74) years for PWoH. The readmission risk was 20.9% for PWH and 12.2% for PWoH (age-adjusted-RR:1.88 [95%CI = 1.84-1.92]). Stratified by age and sex, young female (age 18-29 and 30-39 years) PWH had a higher readmission risk than young female PWoH (aRR = 3.50 [95%CI = 3.11-3.88] and aRR = 4.00 [95%CI = 3.67-4.32], respectively). While the readmission risk increased with age among PWoH, the readmission risk was persistently high across all age groups among PWH. The readmission risk exceeded 30% for PWH admitted for hypertensive heart disease, heart failure, and chronic kidney disease. Interpretation: PWH have a disproportionately higher risk of readmission than PWoH, which is concerning given the aging profile of PWH. More efforts are needed to address readmissions among PWH. Funding: US National Institutes of Health.
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BACKGROUND: Hospital readmission trends for persons with human immunodeficiency virus (PWH) in North America in the context of policy changes, improved antiretroviral therapy (ART), and aging are not well-known. We examined readmissions during 2005-2018 among adult PWH in NA-ACCORD. METHODS: Linear risk regression estimated calendar trends in 30-day readmissions, adjusted for demographics, CD4 count, AIDS history, virologic suppression (<400 copies/mL), and cohort. RESULTS: We examined 20 189 hospitalizations among 8823 PWH (73% cisgender men, 38% White, 38% Black). PWH hospitalized in 2018 versus 2005 had higher median age (54 vs 44 years), CD4 count (469 vs 274 cells/µL), and virologic suppression (83% vs 49%). Unadjusted 30-day readmissions decreased from 20.1% (95% confidence interval [CI], 17.9%-22.3%) in 2005 to 16.3% (95% CI, 14.1%-18.5%) in 2018. Absolute annual trends were -0.34% (95% CI, -.48% to -.19%) in unadjusted and -0.19% (95% CI, -.35% to -.02%) in adjusted analyses. By index hospitalization reason, there were significant adjusted decreases only for cardiovascular and psychiatric hospitalizations. Readmission reason was most frequently in the same diagnostic category as the index hospitalization. CONCLUSIONS: Readmissions decreased over 2005-2018 but remained higher than the general population's. Significant decreases after adjusting for CD4 count and virologic suppression suggest that factors alongside improved ART contributed to lower readmissions. Efforts are needed to further prevent readmissions in PWH.
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Infecciones por VIH , Readmisión del Paciente , Adulto , Masculino , Humanos , Estados Unidos/epidemiología , VIH , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Estudios de Cohortes , Canadá/epidemiologíaRESUMEN
OBJECTIVE: To describe the prevalence of diagnosed depression, anxiety, bipolar disorder, and schizophrenia in people with HIV (PWH) and the differences in HIV care continuum outcomes in those with and without mental health disorders (MHDs). DESIGN: Observational study of participants in the North American AIDS Cohort Collaboration on Research and Design. METHODS: PWH (≥18âyears) contributed data on prevalent schizophrenia, anxiety, depressive, and bipolar disorders from 2008 to 2018 based on International Classification of Diseases code mapping. Mental health (MH) multimorbidity was defined as having two or more MHD. Log binomial models with generalized estimating equations estimated adjusted prevalence ratios (aPR) and 95% confidence intervals for retention in care (≥1âvisit/year) and viral suppression (HIV RNA ≤200âcopies/ml) by presence vs. absence of each MHD between 2016 and 2018. RESULTS: Among 122 896 PWH, 67 643 (55.1%) were diagnosed with one or more MHD: 39% with depressive disorders, 28% with anxiety disorders, 10% with bipolar disorder, and 5% with schizophrenia. The prevalence of depressive and anxiety disorders increased between 2008 and 2018, whereas bipolar disorder and schizophrenia remained stable. MH multimorbidity affected 24% of PWH. From 2016 to 2018 (Nâ=â64 684), retention in care was marginally lower among PWH with depression or anxiety, however those with MH multimorbidity were more likely to be retained in care. PWH with bipolar disorder had marginally lower prevalence of viral suppression (aPRâ=â0.98 [0.98-0.99]) as did PWH with MH multimorbidity (aPRâ=â0.99 [0.99-1.00]) compared with PWH without MHD. CONCLUSION: The prevalence of MHD among PWH was high, including MH multimorbidity. Although retention and viral suppression were similar to people without MHD, viral suppression was lower in those with bipolar disorder and MH multimorbidity.
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Infecciones por VIH , Trastornos Mentales , Humanos , Salud Mental , Prevalencia , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Trastornos Mentales/epidemiología , Trastornos de Ansiedad/epidemiología , Continuidad de la Atención al PacienteRESUMEN
OBJECTIVE: To characterize the prevalence of anemia and risk factors between 2007 and 2017 for moderate/severe anemia among people with HIV (PWH) in North America who have initiated antiretroviral therapy (ART). DESIGN: Observational study of participants in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). METHODS: We estimated the annual prevalence between 1 January 2007 and 31 December 2017 of mild (11.0-12.9âg/dl men, 11.0-11.9âg/dl women), moderate (8.0-10.9âg/dl regardless of sex) and severe (<8.0âg/dl regardless of sex) anemia. Poisson regression models with robust variance and general estimating equations estimated crude and adjusted prevalence ratios (aPR) with 95% confidence intervals ([-]) comparing risk factors for moderate/severe vs. no/mild anemia between 2007 and 2017. RESULTS: Among 73 898 PWH we observed 366 755 hemoglobin measurements following ART initiation, 37 301 (50%) had one or more measures of anemia during follow-up (mild = 17 743 [24%]; moderate = 13 383[18%]; severe = 6175 [8%]). Moderate/severe anemia was more prevalent among women, non-Hispanic Black and Hispanic PWH (vs. non-Hispanic white), those with underweight body mass index (<18.5âkg/m2) and with comorbidities and coinfections. Older age had increased prevalence of moderate/severe anemia among males and decreased prevalence among females. Prevalence of moderate/severe anemia was greater among those with lower CD4+ cell count (≤200 cells/µl) [aPR = 2.11 (2.06-2.17)] unsuppressed HIV viral load (>200 copies/ml) [aPR = 1.26 (1.23-1.29)] and within the first 6 months of ART initiation (vs. >1 year of ART) [aPR = 1.66 (1.61-1.72)]. CONCLUSION: The prevalence of anemia among PWH is reduced after ART initiation but remains high. Risk factors differ by sex and include comorbidities and HIV disease severity. The persistent, substantial prevalence of anemia among PWH merits further investigation, targeted screening, and clinical interventions.
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Anemia , Infecciones por VIH , Masculino , Humanos , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Prevalencia , Factores de Riesgo , América del Norte/epidemiología , Anemia/epidemiología , Anemia/etiología , Recuento de Linfocito CD4RESUMEN
Importance: Understanding the severity of postvaccination SARS-CoV-2 (ie, COVID-19) breakthrough illness among people with HIV (PWH) can inform vaccine guidelines and risk-reduction recommendations. Objective: To estimate the rate and risk of severe breakthrough illness among vaccinated PWH and people without HIV (PWoH) who experience a breakthrough infection. Design, Setting, and Participants: In this cohort study, the Corona-Infectious-Virus Epidemiology Team (CIVET-II) collaboration included adults (aged ≥18 years) with HIV who were receiving care and were fully vaccinated by June 30, 2021, along with PWoH matched according to date fully vaccinated, age group, race, ethnicity, and sex from 4 US integrated health systems and academic centers. Those with postvaccination COVID-19 breakthrough before December 31, 2021, were eligible. Exposures: HIV infection. Main Outcomes and Measures: The main outcome was severe COVID-19 breakthrough illness, defined as hospitalization within 28 days after a breakthrough SARS-CoV-2 infection with a primary or secondary COVID-19 discharge diagnosis. Discrete time proportional hazards models estimated adjusted hazard ratios (aHRs) and 95% CIs of severe breakthrough illness within 28 days of breakthrough COVID-19 by HIV status adjusting for demographic variables, COVID-19 vaccine type, and clinical factors. The proportion of patients who received mechanical ventilation or died was compared by HIV status. Results: Among 3649 patients with breakthrough COVID-19 (1241 PWH and 2408 PWoH), most were aged 55 years or older (2182 patients [59.8%]) and male (3244 patients [88.9%]). The cumulative incidence of severe illness in the first 28 days was low and comparable between PWoH and PWH (7.3% vs 6.7%; risk difference, -0.67%; 95% CI, -2.58% to 1.23%). The risk of severe breakthrough illness was 59% higher in PWH with CD4 cell counts less than 350 cells/µL compared with PWoH (aHR, 1.59; 95% CI, 0.99 to 2.46; P = .049). In multivariable analyses among PWH, being female, older, having a cancer diagnosis, and lower CD4 cell count were associated with increased risk of severe breakthrough illness, whereas previous COVID-19 was associated with reduced risk. Among 249 hospitalized patients, 24 (9.6%) were mechanically ventilated and 20 (8.0%) died, with no difference by HIV status. Conclusions and Relevance: In this cohort study, the risk of severe COVID-19 breakthrough illness within 28 days of a breakthrough infection was low among vaccinated PWH and PWoH. PWH with moderate or severe immune suppression had a higher risk of severe breakthrough infection and should be included in groups prioritized for additional vaccine doses and risk-reduction strategies.
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Vacunas contra la COVID-19 , COVID-19 , Infecciones por VIH , Adolescente , Adulto , Femenino , Humanos , Masculino , Estudios de Cohortes , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , SARS-CoV-2RESUMEN
Background People with HIV (PWH) are at an increased risk of cardiovascular disease (CVD) with an unknown added impact of hepatitis C virus (HCV) coinfection. We aimed to identify whether HCV coinfection increases the risk of type 1 myocardial infarction (T1MI) and if the risk differs by age. Methods and Results We used data from NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) from January 1, 2000, to December 31, 2017, PWH (aged 40-79 years) who had initiated antiretroviral therapy. The primary outcome was an adjudicated T1MI event. Those who started direct-acting HCV antivirals were censored at the time of initiation. Crude incidence rates per 1000 person-years were calculated for T1MI by calendar time. Discrete time-to-event analyses with complementary log-log models were used to estimate adjusted hazard ratios and 95% CIs for T1MI among those with and without HCV. Among 23 361 PWH, 4677 (20%) had HCV. There were 89 (1.9%) T1MIs among PWH with HCV and 314 (1.7%) among PWH without HCV. HCV was not associated with increased T1MI risk in PWH (adjusted hazard ratio, 0.98 [95% CI, 0.74-1.30]). However, the risk of T1MI increased with age and was amplified in those with HCV (adjusted hazard ratio per 10-year increase in age, 1.85 [95% CI, 1.38-2.48]) compared with those without HCV (adjusted hazard ratio per 10-year increase in age,1.30 [95% CI, 1.13-1.50]; P<0.001, test of interaction). Conclusions HCV coinfection was not significantly associated with increased T1MI risk; however, the risk of T1MI with increasing age was greater in those with HCV compared with those without, and HCV status should be considered when assessing CVD risk in aging PWH.
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Enfermedades Cardiovasculares , Coinfección , Infecciones por VIH , Hepatitis C , Infarto del Miocardio , Anciano , Envejecimiento , Antivirales/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Coinfección/complicaciones , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Factores de Riesgo de Enfermedad Cardiaca , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Humanos , Lactante , Infarto del Miocardio/epidemiología , Factores de RiesgoRESUMEN
We describe the design, implementation, and impact of a data harmonization, data quality checking, and dynamic report generation application in an international observational HIV research network. The IeDEA Harmonist Data Toolkit is a web-based application written in the open source programming language R, employs the R/Shiny and RMarkdown packages, and leverages the REDCap data collection platform for data model definition and user authentication. The Toolkit performs data quality checks on uploaded datasets, checks for conformance with the network's common data model, displays the results both interactively and in downloadable reports, and stores approved datasets in secure cloud storage for retrieval by the requesting investigator. Including stakeholders and users in the design process was key to the successful adoption of the application. A survey of regional data managers as well as initial usage metrics indicate that the Toolkit saves time and results in improved data quality, with a 61% mean reduction in the number of error records in a dataset. The generalized application design allows the Toolkit to be easily adapted to other research networks.
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Exactitud de los Datos , Infecciones por VIH , Recolección de Datos , Humanos , Difusión de la Información , Programas InformáticosRESUMEN
Importance: Recommendations for additional doses of COVID-19 vaccines for people with HIV (PWH) are restricted to those with advanced disease or unsuppressed HIV viral load. Understanding SARS-CoV-2 infection risk after vaccination among PWH is essential for informing vaccination guidelines. Objective: To estimate the rate and risk of breakthrough infections among fully vaccinated PWH and people without HIV (PWoH) in the United States. Design, Setting, and Participants: This cohort study used the Corona-Infectious-Virus Epidemiology Team (CIVET)-II (of the North American AIDS Cohort Collaboration on Research and Design [NA-ACCORD], which is part of the International Epidemiology Databases to Evaluate AIDS [IeDEA]), collaboration of 4 prospective, electronic health record-based cohorts from integrated health systems and academic health centers. Adult PWH who were fully vaccinated prior to June 30, 2021, were matched with PWoH on date of full vaccination, age, race and ethnicity, and sex and followed up through December 31, 2021. Exposures: HIV infection. Main Outcomes and Measures: COVID-19 breakthrough infections, defined as laboratory evidence of SARS-CoV-2 infection or COVID-19 diagnosis after a patient was fully vaccinated. Results: Among 113â¯994 patients (33â¯029 PWH and 80â¯965 PWoH), most were 55 years or older (80â¯017 [70%]) and male (104â¯967 [92%]); 47â¯098 (41%) were non-Hispanic Black, and 43â¯218 (38%) were non-Hispanic White. The rate of breakthrough infections was higher in PWH vs PWoH (55 [95% CI, 52-58] cases per 1000 person-years vs 43 [95% CI, 42-45] cases per 1000 person-years). Cumulative incidence of breakthroughs 9 months after full vaccination was low (3.8% [95% CI, 3.7%-3.9%]), albeit higher in PWH vs PWoH (4.4% vs 3.5%; log-rank P < .001; risk difference, 0.9% [95% CI, 0.6%-1.2%]) and within each vaccine type. Breakthrough infection risk was 28% higher in PWH vs PWoH (adjusted hazard ratio, 1.28 [95% CI, 1.19-1.37]). Among PWH, younger age (<45 y vs 45-54 y), history of COVID-19, and not receiving an additional dose (aHR, 0.71 [95% CI, 0.58-0.88]) were associated with increased risk of breakthrough infections. There was no association of breakthrough with HIV viral load suppression, but high CD4 count (ie, ≥500 cells/mm3) was associated with fewer breakthroughs among PWH. Conclusions and Relevance: In this study, COVID-19 vaccination, especially with an additional dose, was effective against infection with SARS-CoV-2 strains circulating through December 31, 2021. PWH had an increased risk of breakthrough infections compared with PWoH. Expansion of recommendations for additional vaccine doses to all PWH should be considered.
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Síndrome de Inmunodeficiencia Adquirida , COVID-19 , Infecciones por VIH , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Adulto , COVID-19/epidemiología , COVID-19/prevención & control , Prueba de COVID-19 , Vacunas contra la COVID-19/uso terapéutico , Estudios de Cohortes , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Masculino , Estudios Prospectivos , SARS-CoV-2 , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Adults aged 50 years or older comprise a majority of people with HIV in the USA. Our objective was to describe observed differences by age in CD4 count at entry into HIV care, timing of antiretroviral therapy (ART) prescription, and CD4 count at time of ART prescription before (2004-11) and during (2012-18) the current era of universal treatment. METHODS: For this descriptive study, we calculated median (IQR) CD4 count at entry into care, days from entry into care to ART prescription, and CD4 count at time of ART prescription among patients enrolled in US-based clinical cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD; see appendix). We excluded participants with no CD4 count recorded at entry into care, medical records that suggested previous ART use, or previous AIDS diagnosis. All calculations were stratified by age (≥50 and 18-50 years) and calendar year. FINDINGS: Of 35â 293 ART-naive adult participants entering care between Jan 1, 2004 and Dec 31, 2018, 5794 (16%) were women and 29â 499 (84%) were men; 15817 (45%) were Black, 11566 (33%) were White, 5538 (16%) were Hispanic (any race), 737 (2%) were Asian or Pacific Islander, 152 (0.4%) were Indigenous, and 98 (0.3%) were multiracial. Median age at entry into care was 39 years (IQR 29-49); 8004 (23%) were aged 50 years or older. Of 29â 141 participants initially prescribed ART, 7274 (25%) were aged 50 years or older. From 2004 to 2018, median CD4 count at entry into care increased from 228 cells per µL (IQR 80-422) to 295 cells per µL (134-489) among adults aged 50 years and older, and from 297 cells per µL (119-480) to 378 cells per µL (202-564) among adults younger than 50 years. Median days from entry into care to ART prescription declined from 56 (IQR 17-658) to 6 (0-15) among adults older than 50 years, and from 61 (17-509) to 6 (0-16) among adults younger than 50 years. Median CD4 count at time of ART prescription increased from 139 cells per µL (IQR 59-257) to 311 cells per µL (137-504) among adults aged 50 years or older, and from 166 cells per µL (49-287) to 377 cells per µL (198-564) among adults younger than 50 years. INTERPRETATION: Before the release of universal treatment guidelines by the US Department of Health and Human Services in 2012, median time to ART prescription was already falling, leading to increases in median CD4 count at ART prescription for both age groups; both measures continued to improve in the treat-all era. However, median CD4 counts, both at entry into care and at ART prescription, among adults aged 50 years and older were lower than those of adults younger than 50 years throughout the study period. Furthermore, even into the treat-all era, over half of adults aged 50 years and older entered care with CD4 counts of less than 350 cells per µL, potentially because of factors including immunosenescence, delayed HIV diagnosis, and late presentation to care. Given that age-related immunological changes might not be fully avoidable, targeted strategies for increasing HIV risk awareness, routine testing, and immediate linkage to HIV care at diagnosis are particularly essential for this population. FUNDING: US National Institutes of Health grant U01AI069918.
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Síndrome de Inmunodeficiencia Adquirida , Fármacos Anti-VIH , Infecciones por VIH , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Anciano , Fármacos Anti-VIH/uso terapéutico , Antirretrovirales/uso terapéutico , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prescripciones , Carga ViralRESUMEN
Since the pioneering work of Thomas Gold, published in 1948, it has been known that we owe our sensitive sense of hearing to a process in the inner ear that can amplify incident sounds on a cycle-by-cycle basis. Called the active process, it uses energy to counteract the viscous dissipation associated with sound-evoked vibrations of the ear's mechanotransduction apparatus. Despite its importance, the mechanism of the active process and the proximate source of energy that powers it have remained elusive, especially at the high frequencies characteristic of amniote hearing. This is partly due to our insufficient understanding of the mechanotransduction process in hair cells, the sensory receptors and amplifiers of the inner ear. It has been proposed previously that cyclical binding of Ca2+ ions to individual mechanotransduction channels could power the active process. That model, however, relied on tailored reaction rates that structurally forced the direction of the cycle. Here we ground our study on our previous model of hair-cell mechanotransduction, which relied on cooperative gating of pairs of channels, and incorporate into it the cyclical binding of Ca2+ ions. With a single binding site per channel and reaction rates drawn from thermodynamic principles, the current model shows that hair cells behave as nonlinear oscillators that exhibit Hopf bifurcations, dynamical instabilities long understood to be signatures of the active process. Using realistic parameter values, we find bifurcations at frequencies in the kilohertz range with physiological Ca2+ concentrations. The current model relies on the electrochemical gradient of Ca2+ as the only energy source for the active process and on the relative motion of cooperative channels within the stereociliary membrane as the sole mechanical driver. Equipped with these two mechanisms, a hair bundle proves capable of operating at frequencies in the kilohertz range, characteristic of amniote hearing.
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Células Ciliadas Auditivas , Mecanotransducción Celular , Oído , Audición/fisiología , Mecanotransducción Celular/fisiología , ViscosidadRESUMEN
Late presentation for care is a major impediment to the prevention and effective treatment of HIV infection. Older individuals are at increased risk of late presentation, represent a growing proportion of people with late presentation, and might require interventions tailored to their age group. We provide a summary of the literature published globally between 2016-21 (reporting data from 1984-2018) and quantify the association of age with delayed presentation. Using the most common definitions of late presentation and older age from these earlier studies, we update this work with data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium, focusing on data from 2000-19, encompassing four continents. Finally, we consider how late presentation among older individuals might be more effectively addressed as electronic medical records become widely adopted.
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Infecciones por VIH , Recuento de Linfocito CD4 , Diagnóstico Tardío , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Humanos , Factores de RiesgoRESUMEN
IMPORTANCE: Recommendations for additional doses of COVID vaccine are restricted to people with HIV who have advanced disease or unsuppressed HIV viral load. Understanding SARS-CoV-2 infection risk post-vaccination among PWH is essential for informing vaccination guidelines. OBJECTIVE: Estimate the risk of breakthrough infections among fully vaccinated people with (PWH) and without (PWoH) HIV in the US. DESIGN SETTING AND PARTICIPANTS: The Corona-Infectious-Virus Epidemiology Team (CIVET)-II cohort collaboration consists of 4 longitudinal cohorts from integrated health systems and academic health centers. Each cohort identified individuals â¥18 years old, in-care, and fully vaccinated for COVID-19 through 30 June 2021. PWH were matched to PWoH on date fully vaccinated, age group, race/ethnicity, and sex at birth. Incidence rates per 1,000 person-years and cumulative incidence of breakthrough infections with 95% confidence intervals ([,]) were estimated by HIV status. Cox proportional hazards models estimated adjusted hazard ratios (aHR) of breakthrough infections by HIV status adjusting for demographic factors, prior COVID-19 illness, vaccine type (BNT162b2, [Pfizer], mRNA-1273 [Moderna], Jansen Ad26.COV2.S [J&J]), calendar time, and cohort. Risk factors for breakthroughs among PWH, were also investigated. EXPOSURE: HIV infection. OUTCOME: COVID-19 breakthrough infections, defined as laboratory evidence of SARS-CoV-2 infection or COVID-19 diagnosis after an individual was fully vaccinated. RESULTS: Among 109,599 individuals (31,840 PWH and 77,759 PWoH), the rate of breakthrough infections was higher in PWH versus PWoH: 44 [41, 48] vs. 31 [29, 33] per 1,000 person-years. Cumulative incidence at 210 days after date fully vaccinated was low, albeit higher in PWH versus PWoH overall (2.8% versus 2.1%, log-rank p<0.001, risk difference=0.7% [0.4%, 1.0%]) and within each vaccine type. Breakthrough infection risk was 41% higher in PWH versus PWoH (aHR=1.41 [1.28, 1.56]). Among PWH, younger age (18-24 versus 45-54), history of COVID-19 prior to fully vaccinated date, and J&J vaccination (versus Pfizer) were associated with increased risk of breakthroughs. There was no association of breakthrough with HIV viral load suppression or CD4 count among PWH. CONCLUSIONS AND RELEVANCE: COVID-19 vaccination is effective against infection with SARS-CoV-2 strains circulating through 30 Sept 2021. PWH have an increased risk of breakthrough infections compared to PWoH. Recommendations for additional vaccine doses should be expanded to all PWH.
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BACKGROUND: Persons with human immunodeficiency virus (PWH) with persistently low CD4 counts despite efficacious antiretroviral therapy could have higher hospitalization risk. METHODS: In 6 US and Canadian clinical cohorts, PWH with virologic suppression for ≥1 year in 2005-2015 were followed until virologic failure, loss to follow-up, death, or study end. Stratified by early (years 2-5) and long-term (years 6-11) suppression and lowest presuppression CD4 count <200 and ≥200 cells/µL, Poisson regression models estimated hospitalization incidence rate ratios (aIRRs) comparing patients by time-updated CD4 count category, adjusted for cohort, age, gender, calendar year, suppression duration, and lowest presuppression CD4 count. RESULTS: The 6997 included patients (19 980 person-years) were 81% cisgender men and 40% white. Among patients with lowest presuppression CD4 count <200 cells/µL (44%), patients with current CD4 count 200-350 vs >500 cells/µL had aIRRs of 1.44 during early suppression (95% confidence interval [CI], 1.01-2.06), and 1.67 (95% CI, 1.03-2.72) during long-term suppression. Among patients with lowest presuppression CD4 count ≥200 (56%), patients with current CD4 351-500 vs >500 cells/µL had an aIRR of 1.22 (95% CI, .93-1.60) during early suppression and 2.09 (95% CI, 1.18-3.70) during long-term suppression. CONCLUSIONS: Virologically suppressed patients with lower CD4 counts experienced higher hospitalization rates and could potentially benefit from targeted clinical management strategies.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH , Hospitalización/estadística & datos numéricos , Recuento de Linfocito CD4 , Canadá , Estudios de Cohortes , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Carga ViralRESUMEN
BACKGROUND: To assess the possible impact of antiretroviral therapy improvements, aging, and comorbidities, we examined trends in all-cause and cause-specific hospitalization rates among persons with HIV (PWH) from 2005 to 2015. METHODS: In 6 clinical cohorts, we followed PWH in care (≥1 outpatient CD4 count or HIV load [VL] every 12 months) and categorized ICD codes of primary discharge diagnoses using modified Clinical Classifications Software. Poisson regression estimated hospitalization rate ratios for calendar time trends, adjusted for demographics, HIV risk factor, and annually updated age, CD4, and VL. RESULTS: Among 28â 057 patients (125â 724 person-years), from 2005 to 2015, the median CD4 increased from 389 to 580 cells/µL and virologic suppression from 55% to 85% of patients. Unadjusted all-cause hospitalization rates decreased from 22.3 per 100 person-years in 2005 (95% confidence interval [CI], 20.6-24.1) to 13.0 in 2015 (95% CI, 12.2-14.0). Unadjusted rates decreased for almost all diagnostic categories. Adjusted rates decreased for all-cause, cardiovascular, and AIDS-defining conditions, increased for non-AIDS-defining infection, and were stable for most other categories. CONCLUSIONS: Among PWH with increasing CD4 counts and viral suppression, unadjusted hospitalization rates decreased for all-cause and most cause-specific hospitalizations, despite the potential effects of aging, comorbidities, and cumulative exposure to HIV and antiretrovirals.
Asunto(s)
Infecciones por VIH , Hospitalización/estadística & datos numéricos , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Envejecimiento , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Canadá/epidemiología , Comorbilidad , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Factores de Riesgo , Estados Unidos/epidemiología , Carga ViralRESUMEN
From 2005 to 2018, among 32013 adults with human immunodeficiency virus entering care, median time to antiretroviral therapy (ART) prescription declined from 69 to 6 days, CD4 count at entry into care increased from 300 to 362 cells/µL, and CD4 count at ART prescription increased from 160 to 364 cells/µL.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , VIH , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Prescripciones , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: Use of electronic health records (EHRs) in health research may lead to the false assumption of complete event ascertainment. We estimated "observation windows" (OWs), defined as periods within which the assumption of complete ascertainment of events is more likely to hold, as a quality control approach to reducing the likelihood of this false assumption. We demonstrated the impact of OWs on estimating the rates of type II diabetes mellitus (diabetes) from HIV clinical cohorts. METHODS: Data contributed by 16 HIV clinical cohorts to the NA-ACCORD were used to identify and evaluate OWs for an operationalized definition of diabetes occurrence as a case study. Procedures included (1) gathering cohort-level data; (2) visualizing and summarizing gaps in observations; (3) systematically establishing start and stop dates during which the assumption of complete ascertainment of diabetes events was reasonable; and (4) visualizing the diabetes OWs relative to the cohort open and close dates to identify immortal person-time. We estimated diabetes occurrence event rates and 95% confidence intervals in the most recent decade that data were available (January 1, 2007, to December 31, 2016). RESULTS: The number of diabetes events decreased by 17% with the use of the diabetes OWs; immortal person-time was removed decreasing total person-years by 23%. Consequently, the diabetes rate increased from 1.23 (95% confidence interval [1.20, 1.25]) per 100 person-years to 1.32 [1.29, 1.35] per 100 person-years with the use of diabetes OWs. CONCLUSIONS: As the use of EHR-curated data for event-driven health research continues to expand, OWs have utility as a quality control approach to complete event ascertainment, helping to improve accuracy of estimates by removing immortal person-time when ascertainment is incomplete.
Asunto(s)
Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Registros Electrónicos de Salud/normas , Infecciones por VIH/complicaciones , Control de Calidad , Humanos , IncidenciaRESUMEN
The effect of red blood cells and the undulation of the endothelium on the shear stress in the microvasculature is studied numerically using the lattice Boltzmann-immersed boundary method. The results demonstrate a significant effect of both the undulation of the endothelium and red blood cells on wall shear stress. Our results also reveal that morphological alterations of red blood cells, as occur in certain pathologies, can significantly affect the values of wall shear stress. The resulting fluctuations in wall shear stress greatly exceed the nominal values, emphasizing the importance of the particulate nature of blood as well as a more realistic description of vessel wall geometry in the study of hemodynamic forces. We find that within the channel widths investigated, which correspond to those found in the microvasculature, the inverse minimum distance normalized to the channel width between the red blood cell and the wall is predictive of the maximum wall shear stress observed in straight channels with a flowing red blood cell. We find that the maximum wall shear stress varies several factors more over a range of capillary numbers (dimensionless number relating strength of flow to membrane elasticity) and reduced areas (measure of deflation of the red blood cell) than the minimum wall shear stress. We see that waviness reduces variation in minimum and maximum shear stresses among different capillary and reduced areas.
Asunto(s)
Forma de la Célula , Endotelio Vascular/fisiología , Eritrocitos/citología , Microvasos , Estrés MecánicoRESUMEN
In Maryland, Lyme disease (LD) is the most widely reported tickborne disease. All laboratories and healthcare providers are required to report LD cases to the local health department. Given the large volume of LD reports, the nuances of diagnosing and reporting LD, and the effort required for investigations by local health department staff, surveillance for LD is burdensome and subject to underreporting. To determine the degree to which misclassification occurs in Maryland, we reviewed medical records for a sample of LD reports from 2009. We characterized what proportion of suspected and "not a case" reports could be reclassified as confirmed or probable once additional information was obtained from medical record review, explored the reasons for misclassification, and determined multipliers for a more accurate number of LD cases. We reviewed medical records for reports originally classified as suspected (n = 44) and "not a case" (n = 92). Of these 136 records, 31 (23%) suspected cases and "not a case" reports were reclassified. We calculated multipliers and applied them to the case counts from 2009, and estimate an additional 269 confirmed and probable cases, a 13.3% increase. Reasons for misclassification fell into three general categories: lack of clinical or diagnostic information from the provider; surveillance process errors; and incomplete information provided on laboratory reports. These multipliers can be used to calculate a better approximation of the true number of LD cases in Maryland, but these multipliers only account for underreporting due to misclassification, and do not account for cases that are not reported at all (e.g., LD diagnoses based on erythema migrans alone that are not reported) or for cases that are not investigated. Knowing that misclassification of cases occurs during the existing LD surveillance process underscores the complexities of LD surveillance, which further reinforces the need to find alternative approaches to LD surveillance.
Asunto(s)
Enfermedad de Lyme/diagnóstico , Vigilancia de la Población , Animales , Humanos , Enfermedad de Lyme/epidemiología , Maryland/epidemiología , Estudios RetrospectivosRESUMEN
ATP is a major player as a signaling molecule in blood microcirculation. It is released by red blood cells (RBCs) when they are subjected to shear stresses large enough to induce a sufficient shape deformation. This prominent feature of chemical response to shear stress and RBC deformation constitutes an important link between vessel geometry, flow conditions, and the mechanical properties of RBCs, which are all contributing factors affecting the chemical signals in the process of vasomotor modulation of the precapillary vessel networks. Several in vitro experiments have reported on ATP release by RBCs due to mechanical stress. These studies have considered both intact RBCs as well as cells within which suspected pathways of ATP release have been inhibited. This has provided profound insights to help elucidate the basic governing key elements, yet how the ATP release process takes place in the (intermediate) microcirculation zone is not well understood. We propose here an analytical model of ATP release. The ATP concentration is coupled in a consistent way to RBC dynamics. The release of ATP, or the lack thereof, is assumed to depend on both the local shear stress and the shape change of the membrane. The full chemo-mechanical coupling problem is written in a lattice-Boltzmann formulation and solved numerically in different geometries (straight channels and bifurcations mimicking vessel networks) and under two kinds of imposed flows (shear and Poiseuille flows). Our model remarkably reproduces existing experimental results. It also pinpoints the major contribution of ATP release when cells traverse network bifurcations. This study may aid in further identifying the interplay between mechanical properties and chemical signaling processes involved in blood microcirculation.