Summary Background Primary angle-closure glaucoma is a leading cause of irreversible blindness worldwide. In early-stage disease, intraocular pressure is raised without visual loss. Because the ...crystalline lens has a major mechanistic role, lens extraction might be a useful initial treatment. Methods From Jan 8, 2009, to Dec 28, 2011, we enrolled patients from 30 hospital eye services in five countries. Randomisation was done by a web-based application. Patients were assigned to undergo clear-lens extraction or receive standard care with laser peripheral iridotomy and topical medical treatment. Eligible patients were aged 50 years or older, did not have cataracts, and had newly diagnosed primary angle closure with intraocular pressure 30 mm Hg or greater or primary angle-closure glaucoma. The co-primary endpoints were patient-reported health status, intraocular pressure, and incremental cost-effectiveness ratio per quality-adjusted life-year gained 36 months after treatment. Analysis was by intention to treat. This study is registered, number ISRCTN44464607. Findings Of 419 participants enrolled, 155 had primary angle closure and 263 primary angle-closure glaucoma. 208 were assigned to clear-lens extraction and 211 to standard care, of whom 351 (84%) had complete data on health status and 366 (87%) on intraocular pressure. The mean health status score (0·87 SD 0·12), assessed with the European Quality of Life-5 Dimensions questionnaire, was 0·052 higher (95% CI 0·015–0·088, p=0·005) and mean intraocular pressure (16·6 SD 3·5 mm Hg) 1·18 mm Hg lower (95% CI –1·99 to –0·38, p=0·004) after clear-lens extraction than after standard care. The incremental cost-effectiveness ratio was £14 284 for initial lens extraction versus standard care. Irreversible loss of vision occurred in one participant who underwent clear-lens extraction and three who received standard care. No patients had serious adverse events. Interpretation Clear-lens extraction showed greater efficacy and was more cost-effective than laser peripheral iridotomy, and should be considered as an option for first-line treatment. Funding Medical Research Council.
ObjectiveTo estimate the cost of paediatric asthma from a UK National Health Service (NHS) and societal perspective and explore determinants of these costs.DesignCost analysis based on data from a ...large clinical trial between 2017 and 2019. Case report forms recorded healthcare resource use and productivity losses attributable to asthma over a 12-month period. These were combined with national unit cost data to generate estimates of health service and indirect costs.SettingAsthma clinics in primary and secondary care in England and Scotland.Main outcome measuresCost per asthma attack stratified by highest level of care received. Total annual health service and indirect costs. Modelled effect of sex, age, severity, number of attacks and adherence on total annual costs.ResultsOf 506 children included in the analysis, 252 experienced at least one attack. The mean (SD) cost per attack was £297 (806) (median £46, IQR 40–138) and the mean total annual cost to the NHS was £1086 (2504) (median £462, IQR 296–731). On average, children missed 6 days of school and their carers missed 13 hours of paid work, contributing to a mean annual indirect cost of £412 (879) (median £30, IQR 0–477). Health service costs increased significantly with number of attacks and participant age (>11 years). Indirect costs increased with asthma severity and number of attacks but were found to be lower in older children.ConclusionsPaediatric asthma imparts a significant economic burden on the health service, families and society. Efforts to improve asthma control may generate significant cost savings.Trial registration numberISRCTN 67875351.
This trial of varicose-vein treatments showed no substantial differences in quality of life 6 months after ultrasound-guided foam sclerotherapy, endovenous laser ablation, or surgery, but ...disease-specific quality of life was slightly worse after foam treatment than after surgery.
Ultrasound-guided foam sclerotherapy and thermal ablation techniques such as endovenous laser ablation have become widely used alternatives to surgery for the treatment of varicose veins. Previous randomized trials and meta-analyses have shown these treatments to be effective in terms of short-term technical success and clinician-reported outcomes.
1
–
19
Clinical practice guidelines recommend the use of patient-reported quality of life to assess the outcomes of treatment of varicose veins.
20
Quality of life was a primary outcome measure in two small randomized trials that compared surgery and endovenous laser ablation,
5
,
9
but to our knowledge, it has not been assessed as a primary . . .
In a randomized trial, 798 patients with varicose veins were assigned to undergo laser ablation, foam sclerotherapy, or surgery. At 5 years, disease-specific quality of life was better after laser ...ablation or surgery than after foam sclerotherapy, and cost-effectiveness analysis favored laser ablation.
Background/aimsTo evaluate the cost-effectiveness of non-invasive monitoring tests to detect the onset of neovascular age-related macular degeneration (nAMD) in the unaffected second eye of patients ...receiving treatment for unilateral nAMD in a UK National Health Service (NHS) hospital outpatient setting.MethodsA patient-level state transition model was constructed to simulate the onset, detection, and treatment of nAMD in the second eye. Five index tests were compared: self-reported change in visual function, Amsler test, clinic measured change in visual acuity from baseline, fundus assessment by clinical examination or colour photography, and spectral domain optical coherence tomography (SD-OCT). Diagnosis of nAMD was confirmed by fundus fluorescein angiography (FFA) before prompt initiation of antivascular endothelial growth factor treatment. Quality-adjusted life-years (QALYs) and costs of health and social care were modelled over a 25-year time horizon.ResultsSD-OCT generated more QALYs (SD-OCT, 5.830; fundus assessment, 5.787; Amsler grid, 5.736, patient’s subjective assessment, 5.630; and visual acuity, 5.600) and lower health and social care costs (SD-OCT, £19 406; fundus assessment, £19 649; Amsler grid, £19 751; patient’s subjective assessment, £20 198 and visual acuity, £20 444) per patient compared with other individual monitoring tests. Probabilistic sensitivity analysis indicated a high probability (97%–99%) of SD-OCT being the preferred test across a range of cost-effectiveness thresholds (£13 000–£30 000) applied in the UK NHS.ConclusionsEarly treatment of the second eye following FFA confirmation of SD-OCT positive findings is expected to maintain better visual acuity and health-related quality of life and may reduce costs of health and social care over the lifetime of patients.
Chronic kidney disease (CKD) is a long-term condition requiring treatment such as conservative management, kidney transplantation or dialysis. To optimise the volume of fluid removed during dialysis ...(to avoid underhydration or overhydration), people are assigned a 'target weight', which is commonly assessed using clinical methods, such as weight gain between dialysis sessions, pre- and post-dialysis blood pressure and patient-reported symptoms. However, these methods are not precise, and measurement devices based on bioimpedance technology are increasingly used in dialysis centres. Current evidence on the role of bioimpedance devices for fluid management in people with CKD receiving dialysis is limited.
To evaluate the clinical effectiveness and cost-effectiveness of multiple-frequency bioimpedance devices versus standard clinical assessment for fluid management in people with CKD receiving dialysis.
We searched major electronic databases e.g. MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Science Citation Index and Cochrane Central Register of Controlled Trials (CENTRAL) conference abstracts and ongoing studies. There were no date restrictions. Searches were undertaken between June and October 2016.
Evidence was considered from randomised controlled trials (RCTs) comparing fluid management by multiple-frequency bioimpedance devices and standard clinical assessment in people receiving dialysis, and non-randomised studies evaluating the use of the devices for fluid management in people receiving dialysis. One reviewer extracted data and assessed the risk of bias of included studies. A second reviewer cross-checked the extracted data. Standard meta-analyses techniques were used to combine results from included studies. A Markov model was developed to assess the cost-effectiveness of the interventions.
Five RCTs (with 904 adult participants) and eight non-randomised studies (with 4915 adult participants) assessing the use of the Body Composition Monitor (BCM) Fresenius Medical Care, Bad Homburg vor der Höhe, Germany were included. Both absolute overhydration and relative overhydration were significantly lower in patients evaluated using BCM measurements than for those evaluated using standard clinical methods weighted mean difference -0.44, 95% confidence interval (CI) -0.72 to -0.15,
= 0.003,
= 49%; and weighted mean difference -1.84, 95% CI -3.65 to -0.03;
= 0.05,
= 52%, respectively. Pooled effects of bioimpedance monitoring on systolic blood pressure (SBP) (mean difference -2.46 mmHg, 95% CI -5.07 to 0.15 mmHg;
= 0.06,
= 0%), arterial stiffness (mean difference -1.18, 95% CI -3.14 to 0.78;
= 0.24,
= 92%) and mortality (hazard ratio = 0.689, 95% CI 0.23 to 2.08;
= 0.51) were not statistically significant. The economic evaluation showed that, when dialysis costs were included in the model, the probability of bioimpedance monitoring being cost-effective ranged from 13% to 26% at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year gained. With dialysis costs excluded, the corresponding probabilities of cost-effectiveness ranged from 61% to 67%.
Lack of evidence on clinically relevant outcomes, children receiving dialysis, and any multifrequency bioimpedance devices, other than the BCM.
BCM used in addition to clinical assessment may lower overhydration and potentially improve intermediate outcomes, such as SBP, but effects on mortality have not been demonstrated. If dialysis costs are not considered, the incremental cost-effectiveness ratio falls below £20,000, with modest effects on mortality and/or hospitalisation rates. The current findings are not generalisable to paediatric populations nor across other multifrequency bioimpedance devices.
Services that routinely use the BCM should report clinically relevant intermediate and long-term outcomes before and after introduction of the device to extend the current evidence base.
This study is registered as PROSPERO CRD42016041785.
The National Institute for Health Research Health Technology Assessment programme.
Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded as an emergency condition that ...requires prompt treatment to avoid hospitalisation and to reduce morbidity and mortality. Rapid pre-hospital first-line treatment of convulsive status epilepticus is currently benzodiazepines, administered either by trained caregivers in the community (e.g. buccal midazolam, rectal diazepam) or by trained health professionals via intramuscular or intravenous routes (e.g. midazolam, lorazepam). There is a lack of clarity about the optimal treatment for convulsive status epilepticus in the pre-hospital setting.
To assess the current evidence on the clinical effectiveness and cost-effectiveness of treatments for adults with convulsive status epilepticus in the pre-hospital setting.
We searched major electronic databases, including MEDLINE, EMBASE, PsycInfo
, CINAHL, CENTRAL, NHS Economic Evaluation Database, Health Technology Assessment Database, Research Papers in Economics, and the ISPOR Scientific Presentations Database, with no restrictions on publication date or language of publication. Final searches were carried out on 21 July 2020.
Systematic review of randomised controlled trials assessing adults with convulsive status epilepticus who received treatment before or on arrival at the emergency department. Eligible treatments were any antiepileptic drugs offered as first-line treatments, regardless of their route of administration. Primary outcomes were seizure cessation, seizure recurrence and adverse events. Two reviewers independently screened all citations identified by the search strategy, retrieved full-text articles, extracted data and assessed the risk of bias of the included trials. Results were described narratively.
Four trials (1345 randomised participants, of whom 1234 were adults) assessed the intravenous or intramuscular use of benzodiazepines or other antiepileptic drugs for the pre-hospital treatment of convulsive status epilepticus in adults. Three trials at a low risk of bias showed that benzodiazepines were effective in stopping seizures. In particular, intramuscular midazolam was non-inferior to intravenous lorazepam. The addition of levetiracetam to clonazepam did not show clear advantages over clonazepam alone. One trial at a high risk of bias showed that phenobarbital plus optional phenytoin was more effective in terminating seizures than diazepam plus phenytoin. The median time to seizure cessation from drug administration varied from 1.6 minutes to 15 minutes. The proportion of people with recurrence of seizures ranged from 10.4% to 19.1% in two trials reporting this outcome. Across trials, the rates of respiratory depression among participants receiving active treatments were generally low (from 6.4% to 10.6%). The mortality rate ranged from 2% to 7.6% in active treatment groups and from 6.2% to 15.5% in control groups. Only one study based on retrospective observational data met the criteria for economic evaluation; therefore, it was not possible to draw any robust conclusions on cost-effectiveness.
The limited number of identified trials and their differences in terms of treatment comparisons and outcomes hindered any meaningful pooling of data. None of the included trials was conducted in the UK and none assessed the use of buccal midazolam or rectal diazepam. The review of economic evaluations was hampered by lack of suitable data.
Both intravenous lorazepam and intravenous diazepam administered by paramedics are more effective than a placebo in the treatments of adults with convulsive status epilepticus, and intramuscular midazolam is non-inferior to intravenous lorazepam. Large well-designed clinical trials are needed to establish which benzodiazepines are more effective and preferable in the pre-hospital setting.
This study is registered as PROSPERO CRD42020201953.
This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in
; Vol. 26, No. 20. See the NIHR Journals Library website for further project information.
Neovascular age-related macular degeneration is a leading cause of sight loss, and early detection and treatment is important. For patients with neovascular age-related macular degeneration in one ...eye, it is usual practice to monitor the unaffected eye. The test used to diagnose neovascular age-related macular degeneration, fundus fluorescein angiography, is an invasive test. Non-invasive tests are available, but their diagnostic accuracy is unclear.
The primary objective was to determine the diagnostic monitoring performance of tests for neovascular age-related macular degeneration in the second eye of patients with unilateral neovascular age-related macular degeneration. The secondary objectives were the cost-effectiveness of tests and to identify predictive factors of developing neovascular age-related macular degeneration.
This was a multicentre, prospective, cohort, comparative diagnostic accuracy study in a monitoring setting for up to 3 years. A Cox regression risk prediction model and a Markov microsimulation model comparing cost-effectiveness of the index tests over 25 years were used.
This took place in hospital eye services.
Participants were adults (aged 50-95 years) with newly diagnosed (within the previous 6 weeks) neovascular age-related macular degeneration in one eye and an unaffected second (study) eye who were attending for treatment injections in the first eye and who had a study eye baseline visual acuity of ≥ 68 Early Treatment Diabetic Retinopathy Study letters.
The index tests were Amsler chart (completed by participants), fundus clinical examination, optical coherence tomography, self-reported vision assessment (completed by participants) and visual acuity. The reference standard was fundus fluorescein angiography.
The main outcome measures were sensitivity and specificity; the performance of the risk predictor model; and costs and quality-adjusted life-years.
In total, 552 out of 578 patients who consented from 24 NHS hospitals (
= 16 ineligible;
= 10 withdrew consent) took part. The mean age of the patients was 77.4 years (standard deviation 7.7 years) and 57.2% were female. For the primary analysis, 464 patients underwent follow-up fundus fluorescein angiography and 120 developed neovascular age-related macular degeneration on fundus fluorescein angiography. The diagnostic accuracy sensitivity (%) (95% confidence interval); specificity (%) (95% confidence interval) was as follows: optical coherence tomography 91.7 (85.2 to 95.6); 87.8 (83.8 to 90.9), fundus clinical examination 53.8 (44.8 to 62.5); 97.6 (95.3 to 98.9), Amsler 33.7 (25.1 to 43.5); 81.4 (76.4 to 85.5), visual acuity 30.0 (22.5 to 38.7); 66.3 (61.0 to 71.1) and self-reported vision 4.2 (1.6 to 9.8); 97.0 (94.6 to 98.5). Optical coherence tomography had the highest sensitivity across all secondary analyses. The final prediction model for neovascular age-related macular degeneration in the non-affected eye included smoking status, family history of neovascular age-related macular degeneration, the presence of nodular drusen with or without reticular pseudodrusen, and the presence of pigmentary abnormalities
-statistic 0.66 (95% confidence interval 0.62 to 0.71). Optical coherence tomography monitoring generated the greatest quality-adjusted life-years gained per patient (optical coherence tomography, 5.830; fundus clinical examination, 5.787; Amsler chart, 5.736, self-reported vision, 5.630; and visual acuity, 5.600) for the lowest health-care and social care costs (optical coherence tomography, £19,406; fundus clinical examination, £19,649; Amsler chart, £19,751; self-reported vision, £20,198; and visual acuity, £20,444) over the lifetime of the simulated cohort. Optical coherence tomography dominated the other tests or had an incremental cost-effectiveness ratio below the accepted cost-effectiveness thresholds (£20,000) across the scenarios explored.
The diagnostic performance may be different in an unselected population without any history of neovascular age-related macular degeneration; the prediction model did not include genetic profile data, which might have improved the discriminatory performance.
Optical coherence tomography was the most accurate in diagnosing conversion to neovascular age-related macular degeneration in the fellow eye of patients with unilateral neovascular age-related macular degeneration. Economic modelling suggests that optical coherence tomography monitoring is cost-effective and leads to earlier diagnosis of and treatment for neovascular age-related macular degeneration in the second eye of patients being treated for neovascular age-related macular degeneration in their first eye.
Future works should investigate the role of home monitoring, improved risk prediction models and impact on long-term visual outcomes.
This study was registered as ISRCTN48855678.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
; Vol. 26, No. 8. See the NIHR Journals Library website for further project information.
Acute kidney injury is a serious complication that occurs in the context of an acute critical illness or during a postoperative period. Earlier detection of acute kidney injury may facilitate ...strategies to preserve renal function, prevent further disease progression and reduce mortality. Acute kidney injury diagnosis relies on a rise in serum creatinine levels and/or fall in urine output; however, creatinine is an imperfect marker of kidney function. There is interest in the performance of novel biomarkers used in conjunction with existing clinical assessment, such as NephroCheck
(Astute Medical, Inc., San Diego, CA, USA), ARCHITECT
urine neutrophil gelatinase-associated lipocalin (NGAL) (Abbott Laboratories, Abbott Park, IL, USA), and urine and plasma BioPorto NGAL (BioPorto Diagnostics A/S, Hellerup, Denmark) immunoassays. If reliable, these biomarkers may enable earlier identification of acute kidney injury and enhance management of those with a modifiable disease course.
The objective was to evaluate the role of biomarkers for assessing acute kidney injury in critically ill patients who are considered for admission to critical care.
Major electronic databases, conference abstracts and ongoing studies were searched up to June 2019, with no date restrictions. MEDLINE, EMBASE, Health Technology Assessment Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, Web of Science, World Health Organization Global Index Medicus, EU Clinical Trials Register, International Clinical Trials Registry Platform and ClinicalTrials.gov were searched.
A systematic review and meta-analysis were conducted to evaluate the performance of novel biomarkers for the detection of acute kidney injury and prediction of other relevant clinical outcomes. Random-effects models were adopted to combine evidence. A decision tree was developed to evaluate costs and quality-adjusted life-years accrued as a result of changes in short-term outcomes (up to 90 days), and a Markov model was used to extrapolate results over a lifetime time horizon.
A total of 56 studies (17,967 participants), mainly prospective cohort studies, were selected for inclusion. No studies addressing the clinical impact of the use of biomarkers on patient outcomes, compared with standard care, were identified. The main sources of bias across studies were a lack of information on blinding and the optimal threshold for NGAL. For prediction studies, the reporting of statistical details was limited. Although the meta-analyses results showed the potential ability of these biomarkers to detect and predict acute kidney injury, there were limited data to establish any causal link with longer-term health outcomes and there were considerable clinical differences across studies. Cost-effectiveness results were highly uncertain, largely speculative and should be interpreted with caution in the light of the limited evidence base. To illustrate the current uncertainty, 15 scenario analyses were undertaken. Incremental quality-adjusted life-years were very low across all scenarios, ranging from positive to negative increments. Incremental costs were also small, in general, with some scenarios generating cost savings with tests dominant over standard care (cost savings with quality-adjusted life-year gains). However, other scenarios generated results whereby the candidate tests were more costly with fewer quality-adjusted life-years, and were thus dominated by standard care. Therefore, it was not possible to determine a plausible base-case incremental cost-effectiveness ratio for the tests, compared with standard care.
Clinical effectiveness and cost-effectiveness results were hampered by the considerable heterogeneity across identified studies. Economic model predictions should also be interpreted cautiously because of the unknown impact of NGAL-guided treatment, and uncertain causal links between changes in acute kidney injury status and changes in health outcomes.
Current evidence is insufficient to make a full appraisal of the role and economic value of these biomarkers and to determine whether or not they provide cost-effective improvements in the clinical outcomes of acute kidney injury patients.
Future studies should evaluate the targeted use of biomarkers among specific patient populations and the clinical impact of their routine use on patient outcomes and management.
This study is registered as PROSPERO CRD42019147039.
This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in
; Vol. 26, No. 7. See the NIHR Journals Library website for further project information.
Self-monitoring (self-testing and self-management) could be a valid option for oral anticoagulation therapy monitoring in the NHS, but current evidence on its clinical effectiveness or ...cost-effectiveness is limited.
We investigated the clinical effectiveness and cost-effectiveness of point-of-care coagulometers for the self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy, compared with standard clinic monitoring.
We searched major electronic databases (e.g. MEDLINE, MEDLINE In Process & Other Non-Indexed Citations, EMBASE, Bioscience Information Service, Science Citation Index and Cochrane Central Register of Controlled Trials) from 2007 to May 2013. Reports published before 2007 were identified from the existing Cochrane review (major databases searched from inception to 2007). The economic model parameters were derived from the clinical effectiveness review, other relevant reviews, routine sources of cost data and clinical experts' advice.
We assessed randomised controlled trials (RCTs) evaluating self-monitoring in people with atrial fibrillation or heart valve disease requiring long-term anticoagulation therapy. CoaguChek(®) XS and S models (Roche Diagnostics, Basel, Switzerland), INRatio2(®) PT/INR monitor (Alere Inc., San Diego, CA USA), and ProTime Microcoagulation system(®) (International Technidyne Corporation, Nexus Dx, Edison, NJ, USA) coagulometers were compared with standard monitoring. Where possible, we combined data from included trials using standard inverse variance methods. Risk of bias assessment was performed using the Cochrane risk of bias tool. A de novo economic model was developed to assess the cost-effectiveness over a 10-year period.
We identified 26 RCTs (published in 45 papers) with a total of 8763 participants. CoaguChek was used in 85% of the trials. Primary analyses were based on data from 21 out of 26 trials. Only four trials were at low risk of bias. Major clinical events: self-monitoring was significantly better than standard monitoring in preventing thromboembolic events relative risk (RR) 0.58, 95% confidence interval (CI) 0.40 to 0.84; p = 0.004. In people with artificial heart valves (AHVs), self-monitoring almost halved the risk of thromboembolic events (RR 0.56, 95% CI 0.38 to 0.82; p = 0.003) and all-cause mortality (RR 0.54, 95% CI 0.32 to 0.92; p = 0.02). There was greater reduction in thromboembolic events and all-cause mortality through self-management but not through self-testing. Intermediate outcomes: self-testing, but not self-management, showed a modest but significantly higher percentage of time in therapeutic range, compared with standard care (weighted mean difference 4.44, 95% CI 1.71 to 7.18; p = 0.02). Patient-reported outcomes: improvements in patients' quality of life related to self-monitoring were observed in six out of nine trials. High preference rates were reported for self-monitoring (77% to 98% in four trials). Net health and social care costs over 10 years were £7295 (self-monitoring with INRatio2); £7324 (standard care monitoring); £7333 (self-monitoring with CoaguChek XS) and £8609 (self-monitoring with ProTime). The estimated quality-adjusted life-year (QALY) gain associated with self-monitoring was 0.03. Self-monitoring with INRatio2 or CoaguChek XS was found to have ≈ 80% chance of being cost-effective, compared with standard monitoring at a willingness-to-pay threshold of £20,000 per QALY gained.
Compared with standard monitoring, self-monitoring appears to be safe and effective, especially for people with AHVs. Self-monitoring, and in particular self-management, of anticoagulation status appeared cost-effective when pooled estimates of clinical effectiveness were applied. However, if self-monitoring does not result in significant reductions in thromboembolic events, it is unlikely to be cost-effective, based on a comparison of annual monitoring costs alone. Trials investigating the longer-term outcomes of self-management are needed, as well as direct comparisons of the various point-of-care coagulometers.
This study is registered as PROSPERO CRD42013004944.
The National Institute for Health Research Health Technology Assessment programme.
PDF
