81,069 research outputs found
How to RESPOND to Modern Challenges for People Living with HIV: A Profile for a New Cohort Consortium.
Get PDFBACKGROUND
the International Cohort Consortium of Infectious Disease (RESPOND) is a collaboration dedicated to research on HIV and other infectious diseases.
METHODS
RESPOND is a flexible organization, with several independent substudies operating under one shared governance. HIV-related variables, including full antiretroviral therapy (ART) history, are collected annually for all participants and merged with substudy specific data into a shared data pool. Incident clinical events are reported using standardized forms. Prospective follow-up started 1/10/17 (enrolment) with retrospective data collected back to 01/01/12.
RESULTS
Overall, 17 cohorts from Europe and Australia provided data on 26,258 people living with HIV (PLWH). The majority (43.3%) of the population were white, with men-sex-with-men accounting for 43.3% of the risk for HIV acquisition. The median age was 48 years (IQR 40-56) and 5.2% and 25.5% were known to be co-infected with hepatitis B or C. While 5.3% were ART-naïve, the median duration on ART was 10.1 years (4.8-17.6), with 89.5% having a VL <200 copies/mL and the median CD4 count being 621 cells/µL (438-830). Malignancies (n = 361) and cardiovascular disease (n = 168) were the predominant reported clinical events.
CONCLUSION
RESPOND's large, diverse study population and standardized clinical endpoints puts the consortium in a unique position to respond to the diverse modern challenges for PLWH
How to RESPOND to Modern Challenges for People Living with HIV: A Profile for a New Cohort Consortium
No full textBackground: the International Cohort Consortium of Infectious Disease (RESPOND) is a collaboration dedicated to research on HIV and other infectious diseases. Methods: RESPOND is a flexible organization, with several independent substudies operating under one shared governance. HIV-related variables, including full antiretroviral therapy (ART) history, are collected annually for all participants and merged with substudy specific data into a shared data pool. Incident clinical events are reported using standardized forms. Prospective follow-up started 1/10/17 (enrolment) with retrospective data collected back to 01/01/12. Results: Overall, 17 cohorts from Europe and Australia provided data on 26,258 people living with HIV (PLWH). The majority (43.3%) of the population were white, with men-sex-with-men accounting for 43.3% of the risk for HIV acquisition. The median age was 48 years (IQR 40–56) and 5.2% and 25.5% were known to be co-infected with hepatitis B or C. While 5.3% were ART-naïve, the median duration on ART was 10.1 years (4.8–17.6), with 89.5% having a VL &lt;200 copies/mL and the median CD4 count being 621 cells/µL (438–830). Malignancies (n = 361) and cardiovascular disease (n = 168) were the predominant reported clinical events. Conclusion: RESPOND’s large, diverse study population and standardized clinical endpoints puts the consortium in a unique position to respond to the diverse modern challenges for PLWH
Incidence of dyslipidemia in people with HIV who are treated with integrase inhibitors versus other antiretroviral agents
No full textOBJECTIVE
To compare the incidence of dyslipidemia in people with HIV receiving integrase inhibitors (INSTI) versus boosted protease inhibitors (PI/b) and nonnucleoside reverse transcriptase inhibitors (NNRTI) within RESPOND consortium of prospective cohorts.
METHODS
Participants were eligible if they were at least 18 years, without dyslipidemia and initiated or switched to a three-drug antiretroviral therapy (ART)-regimen consisting of either INSTI, NNRTI, or PI/b for the first time, between 1 January 2012 and 31 December 2018. Dyslipidemia was defined as random total cholesterol more than 240 mg/dl, HDL less than 35 mg/dl, triglyceride more than 200 mg/dl, or initiation of lipid-lowering therapy. Poisson regression was used to determine the adjusted incidence rate ratios. Follow-up was censored after 3 years or upon ART-regimen discontinuation or last lipid measurement or 31 December 2019, whichever occurred first.
RESULTS
Overall, 4577 people with HIV were eligible (INSTI = 66.9%, PI/b = 12.5%, and NNRTI = 20.6%), 1938 (42.3%) of whom were ART-naive. During 1.7 (interquartile range, 0.6-3.0) median years of follow-up, 1460 participants developed dyslipidemia [incidence rate: 191.6 per 1000 person-years, 95% confidence interval (CI) 182.0-201.7]. Participants taking INSTI had a lower incidence of dyslipidemia compared with those on PI/b (adjusted incidence rate ratio 0.71; CI 0.59-0.85), but higher rate compared with those on NNRTI (1.35; CI 1.15-1.58). Compared with dolutegravir, the incidence of dyslipidemia was higher with elvitegravir/cobicistat (1.20; CI 1.00-1.43) and raltegravir (1.24; CI 1.02-1.51), but lower with rilpivirine (0.77; CI 0.63-0.94).
CONCLUSION
In this large consortium of heterogeneous cohorts, dyslipidemia was less common with INSTI than with PI/b. Compared with dolutegravir, dyslipidemia was more common with elvitegravir/cobicistat and raltegravir, but less common with rilpivirine
The UN-SUSTAINABLE Match in HCV Recipients. Evidences from the Italian D-MELD Study on Balancing Donor-Recipient Risk Factors
No full textThe UN-SUSTAINABLE Match in HCV Recipients. Evidences from the Italian D-MELD Study on Balancing Donor-Recipient Risk Factor
The relationship between smoking, current CD4, viral load and cancer in persons living with HIV
Get PDFBACKGROUND: It is unknown if the carcinogenic effect of smoking is influenced by CD4 count and viral load (VL) in persons living with HIV. MATERIAL AND METHODS: RESPOND participants with known smoking status were included. Poisson regression adjusting for baseline confounders investigated the interaction between current CD4/VL strata (good [CD4≥500/mm and VL200 copies/ml] and intermediate [all other combinations]), smoking status and all cancers, non-AIDS defining cancers (NADC), smoking-related cancers (SRC), and infection-related cancers (IRC). RESULTS: Of 19602 persons, 41.3% were never smokers 44.4% current and 14.4% previous smokers at baseline. CD4/VL strata were poor in 3.4%, intermediate in 44.8% and good in 51.8%. There were 513 incident cancers; incidence rate 6.9/1000 PYFU (95% CI 6.3-7.5). Current smokers had higher incidence of all cancer (adjusted incidence rate ratio 1.45; 1.17-1.79), NADC (1.65; 1.31-2.09), SRC (2.21; 1.53-3.20), and IRC (1.38; 0.97-1.96) vs never smokers. Those with poor CD4/VL had increased incidence of all cancer (5.36; 95% CI 3.71-7.75), NADC (3.14; 1.92-5.14), SRC (1.82; 0.76-4.41) and IRC (10.21; 6.06-17.20) versus those with good CD4/VL. There was no evidence that the association between smoking and cancer subtypes differed depending on the CD4/VL strata (p > 0.1, test for interaction). CONCLUSIONS: In the large RESPOND consortium, the impact of smoking on cancer was clear and reducing smoking rates should remain a priority. The association between current immune deficiency, virological control and cancer was similar for never smokers, current smokers and previous smokers suggesting similar carcinogenic effects of smoking regardless of CD4 count and VL
Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation-A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU): Study Protocol and Analysis Plan.
No full textIntroduction: Septic shock remains amongst the leading causes of childhood mortality. Therapeutic options to support children with septic shock refractory to initial resuscitation with fluids and inotropes are limited. Recently, the combination of intravenous hydrocortisone with high dose ascorbic acid and thiamine (HAT therapy), postulated to reduce sepsis-related organ dysfunction, has been proposed as a safe approach with potential for mortality benefit, but randomized trials in paediatric patients are lacking. We hypothesize that protocolised early use of HAT therapy ("metabolic resuscitation") in children with septic shock is feasible and will lead to earlier resolution of organ dysfunction. Here, we describe the protocol of the Resuscitation in Paediatric Sepsis Using Metabolic Resuscitation-A Randomized Controlled Pilot Study in the Paediatric Intensive Care Unit (RESPOND PICU). Methods and Analysis: The RESPOND PICU study is an open label randomized-controlled, two-sided multicentre pilot study conducted in paediatric intensive care units (PICUs) in Australia and New Zealand. Sixty children aged between 28 days and 18 years treated with inotropes for presumed septic shock will be randomized in a 1:1 ratio to either metabolic resuscitation (1 mg/kg hydrocortisone q6h, 30 mg/kg ascorbic acid q6h, 4 mg/kg thiamine q12h) or standard septic shock management. Main outcomes include feasibility of the study protocol and survival free of organ dysfunction censored at 28 days. The study cohort will be followed up at 28-days and 6-months post enrolment to assess neurodevelopment, quality of life and functional status. Biobanking will allow ancillary studies on sepsis biomarkers. Ethics and Dissemination: The study received ethical clearance from Children's Health Queensland Human Research Ethics Committee (HREC/18/QCHQ/49168) and commenced enrolment on June 12th, 2019. The primary study findings will be submitted for publication in a peer-reviewed journal. Trial Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12619000829112). Protocol Version: V1.8 22/7/20.Full Tex
Modelling solutions to the impact of COVID-19 on cardiovascular waiting Lists
No full textThis three-day virtual study group explored the challenges related to the delays in seeking and gaining access to cardiovascular treatments caused by the COVID-19 pandemic and the impact this will have upon waiting lists.Background: cardiovascular disease is the leading cause of death for men in the UK and second-most for women. During the first lockdown from March 2020, elective cardiac procedures and many outpatient consultations were postponed and a substantial number of appointments have not yet been rescheduled. In addition, those who were suffering from heart conditions did not present to their GP or hospital – either because they did not want to impact further on NHS resources, or through concern of being exposed to the virus. Clinicians have been able to report what has been happening with respect to the reduction in emergency cardiac admissions and procedures, as well as quantify the excess deaths from emergency cardiac conditions. They have not quantified the impact on outpatient consultations.It would be helpful to form a predictive model of the outcome of different strategies for recovery of the backlog in cardiac procedures and outpatient consultations, noting that a number of competing elements are at play including incident cases, prevalent cases, delayed cases, abandonment from changes in disease and deaths, as well as the capacity and capability of NHS services to respond. For example, given different strategies for recovery from this major perturbation to treatment, what would be the implications for treatment demand over timescales from say 6 months to several years? How should treatment be optimised given resource constraints? What would be the impact of additional waves of COVID-19 cases?Aims and objectives: this study group brought together researchers and clinicians to provide further insight into these complex challenges through a variety of mathematical approaches.Proposed issues explored related to:1. The overarching state of the delivery of elective cardiovascular procedures and outpatient consultations at the national level, as a result of the pandemic and how this plays out at regional or local (single NHS trust) levels.2. An exemplar procedure - Aortic Stenosis – for which there is a particularly well-defined data set and for which missed early intervention can lead to particularly adverse outcomes over the course of one or two years.3. An exemplar condition – chronic heart failure - treatment regimens for which are less well-defined, yet the missed appointments during the pandemic represent a major perturbation to care that may impact on the optimal management of resources within cardiology departments.These were discussed in light of the following concerns:Where people are not presenting to clinics now, what will the impact of this be further down the line, as their health issue has not gone away? If people don’t present for treatment but don’t die, what impact does that have on resources?What could the knock-on effect of additional lockdowns be?If and when hospitals return to normal, what would be the optimal way to recover from the backlog and avoid a situation where more urgent cases in poorer condition are prioritised over routine earlier interventions, leading to perpetual worse outcomes for everyone.How can we configure a decision support system that could enable day-to-day answers to these questions on the ground?Previous work through V-KEMS discussed general mathematical principles which was considered and a number of different scenarios were modelled.Following the event, Plus Magazine interviewed Dr Jess Enright (University of Glasgow) and Dr Ramesh Nadarajah (University of Leeds). Ramesh presented the challenges at the event and Jess was one of the modelers who helped to develop the event. The inspiring podcast can be heard here. A working paper is published below, which highlights the discussions that took place at the Study Group and the initial findings.<br/
All repair and reconstruction. Techniques from the SANTI study group
Get PDFBackground: Combining an anterior cruciate ligament (ACL) reconstruction with an anterolateral ligament (ALL) reconstruction results in significant advantages including reduced graft rupture rates, a lower risk of reoperation for secondary meniscectomy, improved knee stability, and higher rates of return to preinjury levels of sport. Indications: The previously reported indications for combined ACL and ALL reconstruction are as follows: ACL reconstruction revision; high-grade pivot shift test; long-term ACL rupture; young patients; pivoting activities; concomitant medial meniscus repair, and, specifically, regarding the ALL repair, it must be an acute surgery (within 15 days from injury). Technique Description: Several modern techniques have been described to repair and reconstruct the ALL. This technical note details a number of these techniques performed by the Scientific Anterior Cruciate Ligament Network International (SANTI) Study Group. Results: First, we describe a combined ACL reconstruction and double-bundle ALL reconstruction using hamstring autograft. Secondly, we describe a single-bundle ALL reconstruction using gracilis autograft. Thirdly, we describe an ALL reconstruction technique using a knotless soft anchor, which provides shallow fixation and prevents tunnel convergence. Finally, we describe a technique for ALL repair. Conclusion: Several techniques have been described to repair and reconstruct the ALL, all offering significant advantages over an isolated ACL reconstruction. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication
Robust automated detection of microstructural white matter degeneration in Alzheimer’s disease using machine learning classification of multicenter DTI data
No full textDiffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer’s disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of multicenter acquisition. We included a sample of 137 patients with clinically probable AD (MMSE 20.6±5.3) and 143 healthy elderly controls, scanned in nine different scanners. For diagnostic classification we used the DTI indices fractional anisotropy (FA) and mean diffusivity (MD) and, for comparison, gray matter and white matter density maps from anatomical MRI. Data were classified using a Support Vector Machine (SVM) and a Naïve Bayes (NB) classifier. We used two cross-validation approaches, (i) test and training samples randomly drawn from the entire data set (pooled cross-validation) and (ii) data from each scanner as test set, and the data from the remaining scanners as training set (scanner-specific cross-validation). In the pooled cross-validation, SVM achieved an accuracy of 80% for FA and 83% for MD. Accuracies for NB were significantly lower, ranging between 68% and 75%. Removing variance components arising from scanners using principal component analysis did not significantly change the classification results for both classifiers. For the scanner-specific cross-validation, the classification accuracy was reduced for both SVM and NB. After mean correction, classification accuracy reached a level comparable to the results obtained from the pooled cross-validation. Our findings support the notion that machine learning classification allows robust classification of DTI data sets arising from multiple scanners, even if a new data set comes from a scanner that was not part of the training sample
Alternative monotherapy or add-on therapy in patients with epilepsy whose seizures do not respond to the first monotherapy: an Italian multicenter prospective observational study.
No full textA prospective multicenter observational study was undertaken on children and adults with epilepsy in whom first monotherapy failed, to assess indications and effects of alternative monotherapy vs. polytherapy. Patients were followed until 12-month remission, drug withdrawal, or up to 18months. Monotherapy and polytherapy were compared for patients' baseline features, indication, retention time, remission, adverse events (AE), quality of life, and direct and indirect costs. Included were 157 men and 174 women, aged 2-86years. Of the patients, 72.2% were switched to alternative monotherapy. Baseline treatment was changed for lack of efficacy (73.9%) or adverse events (26.1%). Two hundred forty-three completed the study (remission: 175; 72.0%). Retention time, hospital admissions, days off-work and off-school, and quality of life did not differ between the two treatment groups. Patients were followed for 365.3person-years. Three hundred eighty-three incident AEs were reported by 46.4% of patients in monotherapy and 40.2% in polytherapy (serious AEs: 9.6% vs. 8.7%, mostly nondrug-related)
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