ORCID Profile
0000-0003-3201-1743
Current Organisation
University of Oxford
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Publisher: National Institute for Health and Care Research
Date: 11-2021
DOI: 10.3310/HTA25660
Abstract: Although routine NHS data potentially include all patients, confounding limits their use for causal inference. Methods to minimise confounding in observational studies of implantable devices are required to enable the evaluation of patients with severe systemic morbidity who are excluded from many randomised controlled trials. Stage 1 – replicate the Total or Partial Knee Arthroplasty Trial (TOPKAT), a surgical randomised controlled trial comparing unicompartmental knee replacement with total knee replacement using propensity score and instrumental variable methods. Stage 2 – compare the risk benefits and cost-effectiveness of unicompartmental knee replacement with total knee replacement surgery in patients with severe systemic morbidity who would have been ineligible for TOPKAT using the validated methods from stage 1. This was a cohort study. Data were obtained from the National Joint Registry database and linked to hospital inpatient (Hospital Episode Statistics) and patient-reported outcome data. Stage 1 – people undergoing unicompartmental knee replacement surgery or total knee replacement surgery who met the TOPKAT eligibility criteria. Stage 2 – participants with an American Society of Anesthesiologists grade of ≥ 3. The patients were exposed to either unicompartmental knee replacement surgery or total knee replacement surgery. The primary outcome measure was the postoperative Oxford Knee Score. The secondary outcome measures were 90-day postoperative complications (venous thromboembolism, myocardial infarction and prosthetic joint infection) and 5-year revision risk and mortality. The main outcome measures for the health economic analysis were health-related quality of life (EuroQol-5 Dimensions) and NHS hospital costs. In stage 1, propensity score stratification and inverse probability weighting replicated the results of TOPKAT. Propensity score adjustment, propensity score matching and instrumental variables did not. Stage 2 included 2256 unicompartmental knee replacement patients and 57,682 total knee replacement patients who had severe comorbidities, of whom 145 and 23,344 had linked Oxford Knee Scores, respectively. A statistically significant but clinically irrelevant difference favouring unicompartmental knee replacement was observed, with a mean postoperative Oxford Knee Score difference of 2 points using propensity score stratification no significant difference was observed using inverse probability weighting. Unicompartmental knee replacement more than halved the risk of venous thromboembolism [relative risk 0.33 (95% confidence interval 0.15 to 0.74) using propensity score stratification relative risk 0.39 (95% confidence interval 0.16 to 0.96) using inverse probability weighting]. Unicompartmental knee replacement was not associated with myocardial infarction or prosthetic joint infection using either method. In the long term, unicompartmental knee replacement had double the revision risk of total knee replacement [hazard ratio 2.70 (95% confidence interval 2.15 to 3.38) using propensity score stratification hazard ratio 2.60 (95% confidence interval 1.94 to 3.47) using inverse probability weighting], but half of the mortality [hazard ratio 0.52 (95% confidence interval 0.36 to 0.74) using propensity score stratification insignificant effect using inverse probability weighting]. Unicompartmental knee replacement had lower costs and higher quality-adjusted life-year gains than total knee replacement for stage 2 participants. Although some propensity score methods successfully replicated TOPKAT, unresolved confounding may have affected stage 2. Missing Oxford Knee Scores may have led to information bias. Propensity score stratification and inverse probability weighting successfully replicated TOPKAT, implying that some (but not all) propensity score methods can be used to evaluate surgical innovations and implantable medical devices using routine NHS data. Unicompartmental knee replacement was safer and more cost-effective than total knee replacement for patients with severe comorbidity and should be considered the first option for suitable patients. Further research is required to understand the performance of propensity score methods for evaluating surgical innovations and implantable devices. This trial is registered as EUPAS17435. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 25, No. 66. See the NIHR Journals Library website for further project information.
Publisher: National Institute for Health and Care Research
Date: 06-2022
DOI: 10.3310/KODQ0769
Abstract: Joint replacement surgery has revolutionised the management of degenerative joint disease. Increasing demand for surgery and post-surgical reviews has overwhelmed orthopaedic services and, consequently, many centres have reduced or stopped follow-up. Such disinvestment is without an evidence base and raises questions regarding the consequences to patients. To produce evidence- and consensus-based recommendations as to how, when and on whom follow-up should be conducted. Our research question was ‘Is it safe to disinvest in mid- to late-term follow-up of hip and knee replacement?’. The study comprised three complementary evidence synthesis work packages to inform a final consensus process. Work package 1 was a systematic review of the clinical effectiveness and cost-effectiveness literature. Work package 2 used routine national data sets (i.e. the Clinical Practice Research Datalink–Hospital Episode Statistics, Hospital Episode Statistics–National Joint Registry–patient-reported outcome measures) to identify pre, peri and postoperative predictors of mid- to late-term revision, and prospective data from 560 patients to understand how patients present for revision surgery. Work package 3 used a Markov model to simulate the survival, health-related quality of life and NHS costs of patients following hip or knee replacement surgery. Finally, evidence from work packages 1–3 informed a face-to-face consensus panel, which involved 32 stakeholders. Our overarching statements are as follows: (1) these recommendations apply to post primary hip and knee replacement follow-up (2) the 10-year time point in these recommendations is based on a lack of robust evidence beyond 10 years and (3) in these recommendations, the term ‘complex cases’ refers to in idual patient and surgical factors that may increase the risk of replacement failure. Our recommendations are as follows: for Orthopaedic Data Evaluation Panel 10A* (ODEP-10A*) minimum implants, it is safe to disinvest in routine follow-up from 1 to 10 years post non-complex hip and knee replacement provided that there is rapid access to orthopaedic review (2) for ODEP-10A* minimum implants in complex cases or non-ODEP-10A* minimum implants, periodic follow-up post hip and knee replacement may be required from 1 to 10 years (3) at 10 years post hip and knee replacement, clinical and radiographic evaluation is recommended and (4) after 10 years post hip and knee replacement, frequency of further follow-up should be based on the 10-year assessment (note that ongoing rapid access to orthopaedic review is still required) [Stone M, Smith L, Kingsbury S, Czoski-Murray C, Judge A, Pinedo-Villanueva R, et al . Evidence-based follow-up recommendations following primary hip and knee arthroplasty (UK SAFE). Orthop Proc 2020 102 – B :13. 0.1302/1358-992X.2020.5.013 ]. The current absence of data beyond 10 years restricted the evidence base. For ODEP-10A* prostheses, the UK SAFE programme demonstrated that it is safe to disinvest in routine follow-up in the 1- to 10-year period after non-complex hip and knee replacement. At 10 years, clinical and radiographic review is recommended. Complex cases, implants not meeting the 10A* criteria and follow-up after revision surgery are not covered by this recommendation. The evidence base for follow-up after 10 years requires further evaluation. Further work should establish the most clinically effective and cost-effective model of delivering a rapid access service and evaluate alternative models for follow-up services, such as virtual clinics. Finally, the needs and outcomes of patients who are symptomatic but do not have appropriate follow-up should be investigated. This study is registered as PROSPERO CRD42017053017. This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research Vol. 10, No. 16. See the NIHR Journals Library website for further project information.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.JAD.2016.04.025
Abstract: Previous studies have demonstrated the effectiveness of Internet-based interventions for depression in comparison with usual care. However, evidence on the cost-effectiveness of these interventions when delivered in outpatient clinics is lacking. The aim of this study was to estimate the cost-effectiveness of an Internet-based problem-solving guided self-help intervention in comparison with enhanced usual care for outpatients on a waiting list for face-to-face treatment for major depression. After the waiting list period, participants from both groups received the same treatment at outpatient clinics. An economic evaluation was performed alongside a randomized controlled trial with 12 months follow-up. Outcomes were improvement in depressive symptom severity (measured by CES-D), response to treatment and Quality-Adjusted Life-Years (QALYs). Statistical uncertainty around cost differences and incremental cost-effectiveness ratios were estimated using bootstrapping. Mean societal costs for the intervention group were €1579 higher than in usual care, but this was not statistically significant (95% CI - 1395 to 4382). Cost-effectiveness acceptability curves showed that the maximum probability of the intervention being cost-effective in comparison with usual care was 0.57 at a ceiling ratio of €15,000/additional point of improvement in CES-D, and 0.25 and 0.30 for an additional response to treatment and an extra QALY respectively, at a ceiling ratio of €30,000. Sensitivity analysis showed that from a mental healthcare provider perspective the probability of the intervention being cost-effective was 0.68 for a ceiling ratio of 0 €/additional unit of effect for the CES-D score, response to treatment and QALYs. As the ceiling ratio increased this probability decreased, because the mean costs in the intervention group were lower than the mean costs in the usual care group. The patients in the intervention group showed low adherence to the Internet-based treatment. It is possible that greater adherence would have led to larger clinical effects. Offering an Internet-based intervention to depressed outpatients on waiting list for face-to-face treatment was not considered cost-effective in comparison with enhanced usual care from a societal perspective. There was a high probability of the intervention being cost-effective in comparison with enhanced usual care from the perspective of the mental healthcare provider.
Publisher: Springer Science and Business Media LLC
Date: 31-12-2019
DOI: 10.1007/S40519-019-00841-2
Abstract: Approximately 70% of adults in Mexico are overweight or obese. Unhealthy lifestyle behaviors are also prevalent. We examined the association of three lifestyle behaviors with body mass index (BMI) categories in adults from Mexico. We used publicly available data from the ENSANUT 2016 survey ( n = 6419). BMI was used to categorize participants. Differences in sleep duration, suffering from symptoms of insomnia, TV watching time, time in front of any screen, vigorous physical activity (yes vs no), moderate physical activity ( 30 min/day—yes vs. no) and walking ( 60 min/day—yes vs. no) were compared across BMI groups using adjusted linear and logistic regression analyses. Thirty-nine percent of participants were overweight and 37% obese. Time in front of TV, in front of any screen, sleep duration and physical activity were significantly associated with overweight and obesity. Compared to normal weight participants, participants in the obese II category spend on average 0.60 h/day (95% CI 0.36–0.84, p = 0.001) and participants in the obese III category 0.54 h/day (95% CI 0.19–0.89, p 0.001) more in front of any screen participants in the obese II category reported 0.55 h/day less sleep (95% CI − 0.67 to − 0.43, p 0.001) participants in the obese III category were less likely to engage in vigorous activity (OR = 0.60, 95% CI 0.43–0.84, p ≤ 0.003), or walking (OR = 0.65, 95% CI 0.49–0.88, p = 0.005). Screen time, sleeping hours, and physical activity were associated with overweight and obesity. However, these associations were not consistent across all BMI categories. Assuming established causal connections, overweight in iduals and in iduals with obesity would benefit from reduced screen time and engaging in moderate/vigorous physical activity. Level III: observational case-control analytic study.
Publisher: Cold Spring Harbor Laboratory
Date: 21-07-2020
DOI: 10.1101/2020.07.17.20156059
Abstract: Concern has been raised in the rheumatological community regarding recent regulatory warnings that hydroxychloroquine used in the COVID-19 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation, or psychosis associated with hydroxychloroquine as used for rheumatoid arthritis (RA). New user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and US). RA patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine (active comparator) and followed up in the short (30-day) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation, and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HR), with estimates pooled where I 2 %. 918,144 and 290,383 users of hydroxychloroquine and sulfasalazine, respectively, were included. No consistent risk of psychiatric events was observed with short-term hydroxychloroquine (compared to sulfasalazine) use, with meta-analytic HRs of 0.96 [0.79-1.16] for depression, 0.94 [0.49-1.77] for suicide/suicidal ideation, and 1.03 [0.66-1.60] for psychosis. No consistent long-term risk was seen, with meta-analytic HRs 0.94 [0.71-1.26] for depression, 0.77 [0.56-1.07] for suicide/suicidal ideation, and 0.99 [0.72-1.35] for psychosis. Hydroxychloroquine as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation, or psychosis compared to sulfasalazine. No effects were seen in the short or long term. Use at higher dose or for different indications needs further investigation. Registered with EU PAS Reference number EUPAS34497 ( www.encepp.eu/encepp/viewResource.htm?id=34498 ). The full study protocol and analysis source code can be found at hdsi-studies/Covid19EstimationHydroxychloroquine . Recent regulatory warnings have raised concerns of potential psychiatric side effects of hydroxychloroquine at the doses used to treat COVID-19, generating concern in the rheumatological community Serious psychiatric adverse events such as suicide, acute psychosis, and depressive episodes have been identified by the US Food and Drug Administration (FDA) adverse events reporting system and at case report level This is the largest study on the neuro-psychiatric safety of hydroxychloroquine to date, including ,000 users treated for their RA in country-level or private health care systems in Germany, the UK, and the US We find no association between the use of hydroxychloroquine and the risk of depression, suicide/suicidal ideation, or severe psychosis compared to sulfasalazine Our data shows no association between hydroxychloroquine treatment for RA and risk of depression, suicide or psychosis compared to sulfasalazine. These findings do not support stopping or switching hydroxychloroquine treatment as used for RA due to recent concerns based on COVID-19 treated patients.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Spyros Kolovos.