76 research outputs found
Immunothrombosis and complement activation contribute to disease severity and adverse outcome in COVID-19
Recognizing differentiating clinical signs of CLN3 disease (Batten disease) at presentation
Purpose To help differentiate CLN3 (Batten) disease, a devastating childhood metabolic disorder, from the similarly presenting early-onset Stargardt disease (STGD1). Early clinical identification of children with CLN3 disease is essential for adequate referral, counselling and rehabilitation. Methods Medical chart review of 38 children who were referred to a specialized ophthalmological centre because of rapid vision loss. The patients were subsequently diagnosed with either CLN3 disease (18 patients) or early-onset STGD1 (20 patients). Results Both children who were later diagnosed with CLN3 disease, as children who were later diagnosed with early-onset STGD1, initially presented with visual acuity (VA) loss due to macular dystrophy at 5-10 years of age. VA in CLN3 disease decreased significantly faster than in STGD1 (p = 0.01). Colour vision was often already severely affected in CLN3 disease while unaffected or only mildly affected in STGD1. Optic disc pallor on fundoscopy and an abnormal nerve fibre layer on optical coherence tomography were common in CLN3 disease compared to generally unaffected in STGD1. In CLN3 disease, dark-adapted (DA) full-field electroretinogram (ERG) responses were either absent or electronegative. In early-onset STGD1, DA ERG responses were generally unaffected. None of the STGD1 patients had an electronegative ERG. Conclusion Already upon presentation at the ophthalmologist, the retina in CLN3 disease is more extensively and more severely affected compared to the retina in early-onset STGD1. This results in more rapid VA loss, severe colour vision abnormalities and abnormal DA ERG responses as the main differentiating early clinical features of CLN3 disease
Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study
Peer reviewe
Risk of diabetes after para-aortic radiation for testicular cancer
Background: While the risk of diabetes is increased following radiation exposure to the pancreas among childhood cancer survivors, its association among testicular cancer (TC) survivors has not been investigated. Methods: Diabetes risk was studied in 2998 1-year TC survivors treated before 50 years of age with orchidectomy with/without radiotherapy between 1976 and 2007. Diabetes incidence was compared with general population rates. Treatment-specific risk of diabetes was assessed using a case–cohort design. Results: With a median follow-up of 13.4 years, 161 TC survivors were diagnosed with diabetes. Diabetes risk was not increased compared to general population rates (standardised incidence ratios (SIR): 0.9; 95% confidence interval (95% CI): 0.7–1.1). Adjusted for age, para-aortic radiotherapy was associated with a 1.66-fold (95% CI: 1.05–2.62) increased diabetes risk compared to no radiotherapy. The excess hazard increased with 0.31 with every 10 Gy increase in the prescribed radiation dose (95% CI: 0.11–0.51, P = 0.003, adjusted for age and BMI); restricted to irradiated patients the excess hazard increased with 0.33 (95% CI: −0.14 to 0.81, P = 0.169) with every 10 Gy increase in radiation dose. Conclusion: Compared to surgery only, para-aortic irradiation is associated with increased diabetes risk among TC survivors
Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study
BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC
Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study
Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe
Functionele visusklachten : tijdig onderzoek loont
Patients with functional vision disorder (FVD) may present with poor visual acuity, visual field loss, or a combination of the two. This paper illustrates the utility of objective tests in diagnosing FVD. We use sweep visual evoked potentials and eye tracking as objective tests for visual acuity and visual field, respectively. These measurements should be made early in the diagnostic process because appropriate treatment becomes more difficult the longer the patient has been undergoing medical workups and referrals. Additionally, objective proof of better visual functions can be used as confirmation of the absence of a serious organic disorder. The results are used to convince patients and parents that vision is potentially much better than the patient experiences and to explain FVD. Consultation should preferably take place in a multidisciplinary setting with trained ophthalmologists and psychologists
Electroretinogram abnormalities in nonanterior childhood uveitis
Purpose: A major point of concern in uveitis is the development of irreversible retinal changes after inflammation. In this study, we assess how nonanterior childhood uveitis affects retinal function using full-field electroretinography (ERG). Methods: Cross-sectional study. ERGs of 63 uveitis eyes (33 children) were measured according to extended International Society for Clinical Electrophysiology of Vision (ISCEV) protocols. ERG abnormalities were investigated in relation to the following clinical parameters: demographics, uveitis characteristics, including severity of inflammation, treatment, best corrected visual acuity (BCVA), cystoid macular oedema (CME) on optical coherence tomography and fluorescein angiography score. Results: The ERG showed abnormalities in 34 eyes (54%). The most frequent ERG abnormalities were prolonged implicit times of the cone b-wave (37%; n = 23/63) and an abnormal 30-Hz flicker response (implicit time and/or amplitude) (33%; n = 21/63). Factors associated with these ERG abnormalities were CME (p = 0.021) and 3+ vitreous cells (p = 0.021). BCVA in eyes with and without these ERG abnormalities did not statistically differ and was relatively good (median: 0.05 LogMAR, IQR: 0.00–0.15 LogMAR). Conclusion: The ERG is frequently affected in childhood uveitis indicating a global retinal dysfunction. ERG abnormalities seem to be associated with a more severe posterior segment inflammation and a younger age. If an association between ERG abnormalities and long-term visual outcome can be made in the future, these early ERG findings during the course of childhood uveitis have significance for treatment strategies
Electroretinogram abnormalities in nonanterior childhood uveitis
Purpose: A major point of concern in uveitis is the development of irreversible retinal changes after inflammation. In this study, we assess how nonanterior childhood uveitis affects retinal function using full-field electroretinography (ERG). Methods: Cross-sectional study. ERGs of 63 uveitis eyes (33 children) were measured according to extended International Society for Clinical Electrophysiology of Vision (ISCEV) protocols. ERG abnormalities were investigated in relation to the following clinical parameters: demographics, uveitis characteristics, including severity of inflammation, treatment, best corrected visual acuity (BCVA), cystoid macular oedema (CME) on optical coherence tomography and fluorescein angiography score. Results: The ERG showed abnormalities in 34 eyes (54%). The most frequent ERG abnormalities were prolonged implicit times of the cone b-wave (37%; n = 23/63) and an abnormal 30-Hz flicker response (implicit time and/or amplitude) (33%; n = 21/63). Factors associated with these ERG abnormalities were CME (p = 0.021) and 3+ vitreous cells (p = 0.021). BCVA in eyes with and without these ERG abnormalities did not statistically differ and was relatively good (median: 0.05 LogMAR, IQR: 0.00–0.15 LogMAR). Conclusion: The ERG is frequently affected in childhood uveitis indicating a global retinal dysfunction. ERG abnormalities seem to be associated with a more severe posterior segment inflammation and a younger age. If an association between ERG abnormalities and long-term visual outcome can be made in the future, these early ERG findings during the course of childhood uveitis have significance for treatment strategies
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