3,599 research outputs found

    Mortality in patients with successful initial response to highly active antiretroviral therapy is still higher than in non-HIV-infected individuals.

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    Mortality in HIV-infected patients has decreased dramatically since the introduction of highly active antiretroviral therapy (HAART). We analyzed progression to death in a population of 3678 antiretroviral treatment-naive patients from the ATHENA national observational cohort from 24 weeks after the start of HAART. Mortality was compared with that in the general population in the Netherlands matched by age and gender. Only log-transformed CD4 cell count (hazard ratio [HR] = 0.50, 95% confidence interval [CI]: 0.40 to 0.61 per unit increase) and plasma viral load (HR = 0.30, 95% CI: 0.15 to 0.60, HIV RNA level or = 100,000 copies/mL) measured at 24 weeks and infection via intravenous drug use (IDU) (HR = 0.16, 95% CI: 0.10 to 0.26, non-IDU vs. IDU) were significantly associated with progression to death. For non-IDU patients with 600 x 10 CD4 cells/L and an HIV RNA level <100,000 copies/mL at 24 weeks, mortality was predicted to be 5.3 (95% CI: 3.5 to 8.4) and 10.4 (95% CI: 6.4 to 17.4) times higher than in the general population for 25-year-old men and women, respectively, and 1.15 (95% CI: 1.08 to 1.25) and 1.29 (95% CI: 1.16 to 1.50) times higher for 65-year-old men and women, respectively. Hence, mortality in HIV-infected patients with a good initial response to HAART is still higher than in the general population

    Pregnancy is associated with elevation of liver enzymes in HIV-positive women on antiretroviral therapy.

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    The objective of this study is to assess whether pregnancy is associated with an increased risk of liver enzyme elevation (LEE) and severe LEE in HIV-positive women on antiretroviral therapy (ART)

    Trends in diabetic retinopathy screening attendance and associations with vision impairment attributable to diabetes in a large nationwide cohort

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    AIMS: To investigate diabetic retinopathy screening attendance and trends in certified vision impairment caused by diabetic eye disease. METHODS: This was a retrospective study of attendance in three urban UK diabetic eye screening programmes in England. A survival analysis was performed to investigate time from diagnosis to first screen by age and sex. Logistic regression analysis of factors influencing screening attendance during a 15-month reporting period was conducted, as well as analysis of new vision impairment certifications (Certificate of Vision Impairment) in England and Wales from 2009 to 2019. RESULTS: Of those newly registered in the Routine Digital Screening pathway (n = 97 048), 80% attended screening within the first 12 months and 88% by 36 months. Time from registration to first eye screening was longer for people aged 18-34 years, and 20% were unscreened after 3 years. Delay in first screen was associated with increased risk of referable retinopathy. Although 95% of participants (n = 291 296) attended during the 15-month reporting period, uptake varied considerably. Younger age, social deprivation, ethnicity and duration of diabetes were independent predictors of non-attendance and referable retinopathy. Although the last 10 years has seen an overall reduction in vision impairment certification attributable to diabetic eye disease, the incidence of vision impairment in those aged <35 years was unchanged. CONCLUSIONS: Whilst the majority of participants are screened in a timely manner, there is considerable variation in uptake. Young adults, have sub-optimal attendance, and levels of vision impairment in this population have not changed over the last 10 years. There is an urgent need to explore barriers to/enablers of attendance in this group to inform policy initiatives and tailored interventions to address this issue

    Trends in diabetic retinopathy screening attendance and associations with vision impairment attributable to diabetes in a large nationwide cohort

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    AIMS: To investigate diabetic retinopathy screening attendance and trends in certified vision impairment caused by diabetic eye disease. METHODS: This was a retrospective study of attendance in three urban UK diabetic eye screening programmes in England. A survival analysis was performed to investigate time from diagnosis to first screen by age and sex. Logistic regression analysis of factors influencing screening attendance during a 15-month reporting period was conducted, as well as analysis of new vision impairment certifications (Certificate of Vision Impairment) in England and Wales from 2009 to 2019. RESULTS: Of those newly registered in the Routine Digital Screening pathway (n = 97 048), 80% attended screening within the first 12 months and 88% by 36 months. Time from registration to first eye screening was longer for people aged 18-34 years, and 20% were unscreened after 3 years. Delay in first screen was associated with increased risk of referable retinopathy. Although 95% of participants (n = 291 296) attended during the 15-month reporting period, uptake varied considerably. Younger age, social deprivation, ethnicity and duration of diabetes were independent predictors of non-attendance and referable retinopathy. Although the last 10 years has seen an overall reduction in vision impairment certification attributable to diabetic eye disease, the incidence of vision impairment in those aged <35 years was unchanged. CONCLUSIONS: Whilst the majority of participants are screened in a timely manner, there is considerable variation in uptake. Young adults, have sub-optimal attendance, and levels of vision impairment in this population have not changed over the last 10 years. There is an urgent need to explore barriers to/enablers of attendance in this group to inform policy initiatives and tailored interventions to address this issue

    Optimising intravenous salbutamol in children: a phase 2 study

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    OBJECTIVE: The β2-agonists such as salbutamol are the mainstay of asthma management. Pharmacokinetic-pharmacodynamic (PKPD) models to guide paediatric dosing are lacking. We explored the relationship between salbutamol dose, serum concentration, effectiveness and adverse effects in children by developing a PKPD model. DESIGN: A prospective cohort study of children admitted to hospital with acute asthma, who received intravenous salbutamol. SETTING: Children were recruited in two cohorts: the emergency departments of two London hospitals or those retrieved by the Children's Acute Transport Service to three London paediatric intensive care units. PATIENTS: Patients were eligible if aged 1-15 years, admitted for acute asthma and about to receive or receiving intravenous salbutamol. INTERVENTIONS: Treatment was according to local policy. Serial salbutamol plasma levels were taken. Effectiveness measurements were recorded using the Paediatric Asthma Severity Score (PASS). Toxicity measurements included lactate, pH, glucose, heart rate, blood pressure and arrhythmias. PKPD modelling was performed with non-linear mixed-effect models. MAIN OUTCOMES: Fifty-eight children were recruited with 221 salbutamol concentration measurements from 54 children. Median (range) age was 2.9 (1.1-15.2) years, and weight was 13.6 (8-57.3) kg. Ninety-five PASS measurements and 2078 toxicity measurements were obtained. RESULTS: A two-compartment PK model adequately described the time course of salbutamol-plasma concentrations. An EMAX (maximum drug effect) concentration-effect relationship described PASS and toxicity measures. PKPD simulations showed an infusion of 0.5 µg/kg/min (maximum 20 µg/min) for 4 hours after bolus achieves >90% maximal bronchodilation for 12 hours. CONCLUSIONS: A paediatric PKPD model for salbutamol is described. An infusion of 0.5 µg/kg/min after bolus achieves effective bronchodilation. Higher rates are associated with greater tachycardia and hyperglycaemia

    Using Tau Polarization to Discriminate between SUSY Models and Determine SUSY Parameters at ILC

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    In many SUSY models the first SUSY signal in the proposed International Linear Collider is expected to come from the pair production of τ~1\tilde\tau_1, followed by its decay into τ\tau+LSP. We study a simple and robust method of measuring the polarization of this τ\tau in its 1-prong hadronic decay channel,and show how it can be used to discriminate between SUSY models and to determine SUSY parameters.Comment: 9 pages, 5 figures, minor corrections; version published in Phys. Lett.

    Childhood intermittent and persistent rhinitis prevalence and climate and vegetation: A global ecologic analysis

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    Background: The effect of climate change and its effects on vegetation growth, and consequently on rhinitis,are uncertain.Objective: To examine between- and within-country associations of climate measures and the normalizeddifference vegetation index with intermittent and persistent rhinitis symptoms in a global context.Methods: Questionnaire data from 6- to 7-year-olds and 13- to 14-year-olds were collected in phase 3 of theInternational Study of Asthma and Allergies in Childhood. Associations of intermittent (>1 symptom reportbut not for 2 consecutive months) and persistent (symptoms for -2 consecutive months) rhinitis symptomprevalences with temperature, precipitation, vapor pressure, and the normalized difference vegetation indexwere assessed in linear mixed-effects regression models adjusted for gross national income and populationdensity. The mean difference in prevalence per 100 children (with 95% confidence intervals [CIs]) perinterquartile range increase of exposure is reported.Results: The country-level intermittent symptom prevalence was associated with several country-levelclimatic measures, including the country-level mean monthly temperature (6.09-C; 95% CI, 2.06e10.11-C per 10.4-C), precipitation (3.10 mm; 95% CI, 0.46e5.73 mm; per 67.0 mm), and vapor pressure(6.21 hPa; 95% CI, 2.17e10.24 hPa; per 10.4 hPa) among 13- to 14-year-olds (222 center in 94 countries).The center-level persistent symptom prevalence was positively associated with several center-level climaticmeasures. Associations with climate were also found for the 6- to 7-year-olds (132 center in 57countries).Conclusion: Several between- and within-country spatial associations between climatic factors and intermittentand persistent rhinitis symptom prevalences were observed. These results provide suggestive evidencethat climate (and future changes in climate) may influence rhinitis symptom prevalence

    The management of type 2 diabetes with fixed‐ratio combination insulin degludec/liraglutide (IDegLira) versus basal‐bolus therapy (insulin glargine U100 plus insulin aspart): a short‐term cost‐effectiveness analysis in the UK setting

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    Aim: To evaluate the cost‐effectiveness of IDegLira versus basal‐bolus therapy (BBT) with insulin glargine U100 plus up to 4 times daily insulin aspart for the management of type 2 diabetes in the UK. Methods: A Microsoft Excel model was used to evaluate the cost‐utility of IDegLira versus BBT over a 1‐year time horizon. Clinical input data were taken from the treat‐to‐target DUAL VII trial, conducted in patients unable to achieve adequate glycaemic control (HbA1c &lt;7.0%) with basal insulin, with IDegLira associated with lower rates of hypoglycaemia and reduced body mass index (BMI) in comparison with BBT, with similar HbA1c reductions. Costs (expressed in GBP) and event‐related disutilities were taken from published sources. Extensive sensitivity analyses were performed. Results: IDegLira was associated with an improvement of 0.05 quality‐adjusted life years (QALYs) versus BBT, due to reductions in non‐severe hypoglycaemic episodes and BMI with IDegLira. Costs were higher with IDegLira by GBP 303 per patient, leading to an incremental cost‐effectiveness ratio (ICER) of GBP 5924 per QALY gained for IDegLira versus BBT. ICERs remained below GBP 20 000 per QALY gained across a range of sensitivity analyses. Conclusions: IDegLira is a cost‐effective alternative to BBT with insulin glargine U100 plus insulin aspart, providing equivalent glycaemic control with a simpler treatment regimen for patients with type 2 diabetes inadequately controlled on basal insulin in the UK

    Comorbidity indices in people with HIV and considerations for coronavirus disease 2019 outcomes

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    OBJECTIVE: To determine comorbidity indices in persons-with-HIV (PWH) and lifestyle-similar HIV-negative controls. DESIGN: Cross-sectional analysis of the Pharmacokinetic and clinical Observations in PeoPle over fifty (POPPY) cohort study in UK and Ireland. METHODS: The Elixhauser Comorbidity Index (ECI), Charlson Comorbidity Index (CCI) and the Comorbidity Burden Index (CBI) were compared between older PWH and HIV-negative controls using the Mann-Whitney U test; the magnitude of the difference between groups was quantified using the r effect size. RESULTS: The 699 PWH and 304 HIV-negative controls were predominantly male (87.5% vs. 64.0%), white (86.3% vs. 90.0%) and had median ages of 57 and 58 years, respectively. Among PWH, the median (interquartile range (IQR)) CD4+ T-cell count was 624 (475, 811) cells/μl; 98.7% were on antiretroviral therapy. The median (IQR) ECI was 0 (0, 8) and 0 (-3, 1), CCI was 2 (1, 5) and 1 (0, 1) and CBI 8.6 (2.2, 16.8) and 5.9 (0.6, 10.8), respectively. Whilst all three indices were significantly higher in PWH than in controls (p < 0.001 for each), the magnitude of the differences between the two groups were small to medium, with effect sizes (95% confidence interval) of 0.21 (0.16, 0.27), 0.38 (0.32, 0.42) and 0.18 (0.11, 0.23), respectively. CONCLUSIONS: These three comorbidity indices are higher in PWH compared to HIV-negative controls, although the magnitude of differences between groups were small. Differences in the ECI, reportedly associated with poorer COVID-19 outcomes, were driven by more individuals with HIV being within the higher end of the range
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