Gestational diabetes mellitus (GDM) is associated with a higher risk of important adverse outcomes. Practice varies and the best strategy for identifying and treating GDM is unclear.
To estimate the ...clinical effectiveness and cost-effectiveness of strategies for identifying and treating women with GDM.
We analysed individual participant data (IPD) from birth cohorts and conducted systematic reviews to estimate the association of maternal glucose levels with adverse perinatal outcomes; GDM prevalence; maternal characteristics/risk factors for GDM; and the effectiveness and costs of treatments. The cost-effectiveness of various strategies was estimated using a decision tree model, along with a value of information analysis to assess where future research might be worthwhile. Detailed systematic searches of MEDLINE
and MEDLINE In-Process & Other Non-Indexed Citations
, EMBASE, Cumulative Index to Nursing and Allied Health Literature Plus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment database, NHS Economic Evaluation Database, Maternity and Infant Care database and the Cochrane Methodology Register were undertaken from inception up to October 2014.
We identified 58 studies examining maternal glucose levels and outcome associations. Analyses using IPD alone and the systematic review demonstrated continuous linear associations of fasting and post-load glucose levels with adverse perinatal outcomes, with no clear threshold below which there is no increased risk. Using IPD, we estimated glucose thresholds to identify infants at high risk of being born large for gestational age or with high adiposity; for South Asian (SA) women these thresholds were fasting and post-load glucose levels of 5.2 mmol/l and 7.2 mmol/l, respectively and for white British (WB) women they were 5.4 and 7.5 mmol/l, respectively. Prevalence using IPD and published data varied from 1.2% to 24.2% (depending on criteria and population) and was consistently two to three times higher in SA women than in WB women. Lowering thresholds to identify GDM, particularly in women of SA origin, identifies more women at risk, but increases costs. Maternal characteristics did not accurately identify women with GDM; there was limited evidence that in some populations risk factors may be useful for identifying low-risk women. Dietary modification additional to routine care reduced the risk of most adverse perinatal outcomes. Metformin (Glucophage,
Teva UK Ltd, Eastbourne, UK) and insulin were more effective than glibenclamide (Aurobindo Pharma - Milpharm Ltd, South Ruislip, Middlesex, UK). For all strategies to identify and treat GDM, the costs exceeded the health benefits. A policy of no screening/testing or treatment offered the maximum expected net monetary benefit (NMB) of £1184 at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year (QALY). The NMB for the three best-performing strategies in each category (screen only, then treat; screen, test, then treat; and test all, then treat) ranged between -£1197 and -£1210. Further research to reduce uncertainty around potential longer-term benefits for the mothers and offspring, find ways of improving the accuracy of identifying women with GDM, and reduce costs of identification and treatment would be worthwhile.
We did not have access to IPD from populations in the UK outside of England. Few observational studies reported longer-term associations, and treatment trials have generally reported only perinatal outcomes.
Using the national standard cost-effectiveness threshold of £20,000 per QALY it is not cost-effective to routinely identify pregnant women for treatment of hyperglycaemia. Further research to provide evidence on longer-term outcomes, and more cost-effective ways to detect and treat GDM, would be valuable.
This study is registered as PROSPERO CRD42013004608.
The National Institute for Health Research Health Technology Assessment programme.
Abstract
Medical interventions may be more effective in some types of individuals than others and identifying characteristics that modify the effectiveness of an intervention is a cornerstone of ...precision or stratified medicine. The opportunity for detailed examination of treatment-covariate interactions can be an important driver for undertaking an individual participant data (IPD) meta-analysis, rather than a meta-analysis using aggregate data. A number of recent modelling approaches are available. We apply these methods to the Perinatal Antiplatelet Review of International Studies (PARIS) Collaboration IPD dataset and compare estimates between them. We discuss the practical implications of applying these methods, which may be of interest to aid meta-analysists in the use of these, often complex models.
Models compared included the two-stage meta-analysis of interaction terms and one-stage models which fit multiple random effects and separate within and between trial information. Models were fitted for nine covariates and five binary outcomes and results compared.
Interaction terms produced by the methods were generally consistent. We show that where data are sparse and there is low heterogeneity in the covariate distributions across trials, the meta-analysis of interactions may produce unstable estimates and have issues with convergence. In this IPD dataset, varying assumptions by using multiple random effects in one-stage models or using only within trial information made little difference to the estimates of treatment-covariate interaction. Method choice will depend on datasets characteristics and individual preference.
Abstract Objective Meta-analysis of individual patient data (IPD) is the “gold-standard” for synthesizing evidence across several studies. Some studies, however, may only provide aggregate data (AD). ...In this situation researchers might need to combine IPD with AD to utilize all the evidence available. Here, we review applied IPD meta-analysis articles to assess if and how AD is combined with IPD in practice. Study Design and Setting A systematic review of articles identified from bibliographic databases and searches. Results We identified 33 applied IPD articles that combined IPD and AD and 166 that did not. For each article, we recorded the proportion of total studies providing IPD, and found that articles combining IPD and AD had, on average, IPD available in only 64% of studies (compared to 90% in articles not combining IPD and AD). Two different methods were used to combine IPD and AD, the two-stage method and analysis of partially reconstructed IPD, but a review of methodological articles identified two further methods, multilevel modeling and Bayesian hierarchical related regression. We summarize each method to aid practitioners. Conclusion Combining IPD and AD is a relevant issue for evidence synthesis, and the further development and validation of suitable meta-analysis methods is needed.
The influence of topographic and temporal variables on cetacean distribution at a fine-scale is still poorly understood. To study the spatial and temporal distribution of harbour porpoise Phocoena ...phocoena and the poorly known Risso's dolphin Grampus griseus we carried out land-based observations from Bardsey Island (Wales, UK) in summer (2001-2007). Using Kernel analysis and Generalized Additive Models it was shown that porpoises and Risso's appeared to be linked to topographic and dynamic cyclic variables with both species using different core areas (dolphins to the West and porpoises to the East off Bardsey). Depth, slope and aspect and a low variation in current speed (for Risso's) were important in explaining the patchy distributions for both species. The prime temporal conditions in these shallow coastal systems were related to the tidal cycle (Low Water Slack and the flood phase), lunar cycle (a few days following the neap tidal phase), diel cycle (afternoons) and seasonal cycle (peaking in August) but differed between species on a temporary but predictable basis. The measure of tidal stratification was shown to be important. Coastal waters generally show a stronger stratification particularly during neap tides upon which the phytoplankton biomass at the surface rises reaching its maximum about 2-3 days after neap tide. It appeared that porpoises occurred in those areas where stratification is maximised and Risso's preferred more mixed waters. This fine-scale study provided a temporal insight into spatial distribution of two species that single studies conducted over broader scales (tens or hundreds of kilometers) do not achieve. Understanding which topographic and cyclic variables drive the patchy distribution of porpoises and Risso's in a Headland/Island system may form the initial basis for identifying potentially critical habitats for these species.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Risk factors such as blood pressure and serum cholesterol are used, with age, in screening for future cardiovascular disease (CVD) events. The value of using these risk factors with age compared with ...using age alone is not known. We compared screening for future CVD events using age alone with screening using age and multiple risk factors based on regular Framingham risk assessments.
Ten-year CVD risk was estimated using Framingham risk equations in a hypothetical sample population of 500,000 people aged 0-89 years. Risk estimates were used to identify individuals who did and did not have a CVD event over a ten-year period. For screening using age alone (age screening) and screening using multiple risk factors and age (Framingham screening) we estimated the (i) detection rate (sensitivity); (ii) false-positive rate; (iii) proportion of CVD-free years of life lost in affected individuals with positive results (person-years detection rate); and (iv) cost per CVD-free life year gained from preventive treatment.
Age screening using a cut-off of 55 years detected 86% of all first CVD events arising in the population every year and 72% of CVD-free years of life lost for a 24% false-positive rate; for five yearly Framingham screening the false-positive rate was 21% for the same 86% detection rate. The estimated cost per CVD-free year of life gained was £2,000 for age screening and £2,200 for Framingham screening if a Framingham screen costs £150 and the annual cost of preventive treatment is £200.
Age screening for future CVD events is simpler than Framingham screening with a similar screening performance and cost-effectiveness. It avoids blood tests and medical examinations. The advantages of age screening in the prevention of heart attack and stroke warrant considering its use in preference to multiple risk factor screening.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background The optimal approach to oxygen therapy in ST-elevation myocardial infarction (STEMI) is uncertain. Methods A randomized controlled trial was undertaken in which 136 patients presenting ...with their first STEMI uncomplicated by cardiogenic shock or marked hypoxia were randomized to receive high-concentration (6 L/min via medium concentration mask) or titrated oxygen (to achieve oxygen saturation 93%-96%) for 6 hours after presentation. The main outcome variables were 30-day mortality and infarct size assessed by troponin T level at 72 hours. Secondary outcomes included a meta-analysis of mortality data from this study and previous randomized controlled trials, and infarct size was assessed by magnetic resonance imaging at 4 to 6 weeks. Results There were 1 of 68 and 2 of 68 deaths in the high-concentration and titrated oxygen groups, respectively; a meta-analysis including these data with those from the 2 previous studies showed an odds ratio for mortality of high-concentration oxygen compared with room air or titrated oxygen of 2.2 (95% CI 0.8-6.0). There was no significant difference between high-concentration versus titrated oxygen in troponin T (ratio of mean levels 0.74, 95% CI 0.50-1.1, P = .14), infarct mass (mean difference −0.8 g, 95% CI −7.6 to 6.1, P = .82), or percent infarct mass (mean difference −0.6%, 95% CI −5.6 to 4.5, P = .83). Conclusion This study found no evidence of benefit or harm from high-concentration compared with titrated oxygen in initially uncomplicated STEMI. However, our estimates have wide CIs, and as a result, large randomized controlled trials are required to resolve the clinical uncertainty.
Dolphins are typically regarded as highly social animals. However, some individuals live apart from their own species and may come to socialize with people through a recognized series of stages which ...are presented and expanded on in this paper. The term "solitary-sociable dolphins" has been used to describe these animals and such individuals have been identified from several different species and reported in many parts of the world. In many instances, the interactions with people that may follow their original isolation, and which typically become more intense over time, have created situations where the welfare of the animal has been compromised by disturbance, injury, the feeding of inappropriate items and aggressive human behavior. Several solitary-sociable dolphins have also been deliberately injured and killed by humans. People who interact with these dolphins may also put themselves at risk of injury. This paper reports on recent cases drawing on published and unpublished sources. Since 2008, 32 solitary dolphins have been recorded including 27 bottlenose dolphins (25
and two
), two striped dolphins and three common dolphins. Four solitary belugas have also been recorded. There are some ten solitary dolphins and one beluga known at the present time. Laws and guidelines currently in place to protect solitary-sociable dolphins need to be strengthened and interactions with people should be avoided or, at the least, carefully managed to protect both the dolphin and the humans involved in the interaction. Terms, such as disturbance and harassment which are included in laws need to be clearly defined. Additionally, management plans for solitary-sociable dolphins need to be developed and adapted on a case by case basis taking into account the individual dolphin's sex, age, personality, stage of sociability and home range. It is also important that government officials and local stakeholders work together to implement guidelines which set out how the public can observe or interact with the dolphin safely.
A wide range of ablative and non-surgical therapies are available for treating small hepatocellular carcinoma in patients with very early or early-stage disease and preserved liver function.
To ...review and compare the effectiveness of all current ablative and non-surgical therapies for patients with small hepatocellular carcinoma (≤ 3 cm).
Systematic review and network meta-analysis.
Nine databases (March 2021), two trial registries (April 2021) and reference lists of relevant systematic reviews.
Eligible studies were randomised controlled trials of ablative and non-surgical therapies, versus any comparator, for small hepatocellular carcinoma. Randomised controlled trials were quality assessed using the Cochrane Risk of Bias 2 tool and mapped. The comparative effectiveness of therapies was assessed using network meta-analysis. A threshold analysis was used to identify which comparisons were sensitive to potential changes in the evidence. Where comparisons based on randomised controlled trial evidence were not robust or no randomised controlled trials were identified, a targeted systematic review of non-randomised, prospective comparative studies provided additional data for repeat network meta-analysis and threshold analysis. The feasibility of undertaking economic modelling was explored. A workshop with patients and clinicians was held to discuss the findings and identify key priorities for future research.
Thirty-seven randomised controlled trials (with over 3700 relevant patients) were included in the review. The majority were conducted in China or Japan and most had a high risk of bias or some risk of bias concerns. The results of the network meta-analysis were uncertain for most comparisons. There was evidence that percutaneous ethanol injection is inferior to radiofrequency ablation for overall survival (hazard ratio 1.45, 95% credible interval 1.16 to 1.82), progression-free survival (hazard ratio 1.36, 95% credible interval 1.11 to 1.67), overall recurrence (relative risk 1.19, 95% credible interval 1.02 to 1.39) and local recurrence (relative risk 1.80, 95% credible interval 1.19 to 2.71). Percutaneous acid injection was also inferior to radiofrequency ablation for progression-free survival (hazard ratio 1.63, 95% credible interval 1.05 to 2.51). Threshold analysis showed that further evidence could plausibly change the result for some comparisons. Fourteen eligible non-randomised studies were identified (
≥ 2316); twelve had a high risk of bias so were not included in updated network meta-analyses. Additional non-randomised data, made available by a clinical advisor, were also included (
= 303). There remained a high level of uncertainty in treatment rankings after the network meta-analyses were updated. However, the updated analyses suggested that microwave ablation and resection are superior to percutaneous ethanol injection and percutaneous acid injection for some outcomes. Further research on stereotactic ablative radiotherapy was recommended at the workshop, although it is only appropriate for certain patient subgroups, limiting opportunities for adequately powered trials.
Many studies were small and of poor quality. No comparative studies were found for some therapies.
The existing evidence base has limitations; the uptake of specific ablative therapies in the United Kingdom appears to be based more on technological advancements and ease of use than strong evidence of clinical effectiveness. However, there is evidence that percutaneous ethanol injection and percutaneous acid injection are inferior to radiofrequency ablation, microwave ablation and resection.
PROSPERO CRD42020221357.
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme (NIHR award ref: NIHR131224) and is published in full in
; Vol. 27, No. 29. See the NIHR Funding and Awards website for further award information.
Abstract Purpose We aimed to quantify the effect of folic acid supplementation on the prevention of cognitive decline. Methods We conducted a meta-analysis of 9 placebo-controlled randomized trials ...(2835 participants, median duration 6 months) of folic acid, with or without other B vitamins, on cognitive function. Standardized mean differences in cognitive function test scores were calculated between folic acid and placebo-treated groups. Results The standardized mean difference in cognitive function test scores was 0.01 (95% confidence interval 95% CI, −0.08 to 0.10), or an increase of 1% (95% CI, −8% to 10%) of 1 standard deviation. The results were similar within each of the 4 categories of cognitive function (memory, speed, language, and executive function); standardized mean differences were 0.01 (95% CI, −0.08 to 0.09), −0.01 (95% CI, −0.10 to 0.13), −0.05 (95% CI, −0.15 to 0.04), and 0.03 (95% CI, −0.13 to 0.19), respectively. Conclusion Randomized trials show no effect of folic acid, with or without other B vitamins, on cognitive function within 3 years of the start of treatment. Trials of longer duration, recording the incidence of dementia, as well as cognitive decline, are needed.
Background
QAngio
®
XA 3D/QFR
®
(three-dimensional/quantitative flow ratio) imaging software (Medis Medical Imaging Systems BV, Leiden, the Netherlands) and CAAS
®
vFFR
®
(vessel fractional flow ...reserve) imaging software (Pie Medical Imaging BV, Maastricht, the Netherlands) are non-invasive technologies to assess the functional significance of coronary stenoses, which can be alternatives to invasive fractional flow reserve assessment.
Objectives
The objectives were to determine the clinical effectiveness and cost-effectiveness of QAngio XA 3D/QFR and CAAS vFFR.
Methods
We performed a systematic review of all evidence on QAngio XA 3D/QFR and CAAS vFFR, including diagnostic accuracy, clinical effectiveness, implementation and economic analyses. We searched MEDLINE and other databases to January 2020 for studies where either technology was used and compared with fractional flow reserve in patients with intermediate stenosis. The risk of bias was assessed with quality assessment of diagnostic accuracy studies. Meta-analyses of diagnostic accuracy were performed. Clinical and implementation outcomes were synthesised narratively. A simulation study investigated the clinical impact of using QAngio XA 3D/QFR. We developed a de novo decision-analytic model to estimate the cost-effectiveness of QAngio XA 3D/QFR and CAAS vFFR relative to invasive fractional flow reserve or invasive coronary angiography alone. Scenario analyses were undertaken to explore the robustness of the results to variation in the sources of data used to populate the model and alternative assumptions.
Results
Thirty-nine studies (5440 patients) of QAngio XA 3D/QFR and three studies (500 patients) of CAAS vFFR were included. QAngio XA 3D/QFR had good diagnostic accuracy to predict functionally significant fractional flow reserve (≤ 0.80 cut-off point); contrast-flow quantitative flow ratio had a sensitivity of 85% (95% confidence interval 78% to 90%) and a specificity of 91% (95% confidence interval 85% to 95%). A total of 95% of quantitative flow ratio measurements were within 0.14 of the fractional flow reserve. Data on the diagnostic accuracy of CAAS vFFR were limited and a full meta-analysis was not feasible. There were very few data on clinical and implementation outcomes. The simulation found that quantitative flow ratio slightly increased the revascularisation rate when compared with fractional flow reserve, from 40.2% to 42.0%. Quantitative flow ratio and fractional flow reserve resulted in similar numbers of subsequent coronary events. The base-case cost-effectiveness results showed that the test strategy with the highest net benefit was invasive coronary angiography with confirmatory fractional flow reserve. The next best strategies were QAngio XA 3D/QFR and CAAS vFFR (without fractional flow reserve). However, the difference in net benefit between this best strategy and the next best was small, ranging from 0.007 to 0.012 quality-adjusted life-years (or equivalently £140–240) per patient diagnosed at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year.
Limitations
Diagnostic accuracy evidence on CAAS vFFR, and evidence on the clinical impact of QAngio XA 3D/QFR, were limited.
Conclusions
Quantitative flow ratio as measured by QAngio XA 3D/QFR has good agreement and diagnostic accuracy compared with fractional flow reserve and is preferable to standard invasive coronary angiography alone. It appears to have very similar cost-effectiveness to fractional flow reserve and, therefore, pending further evidence on general clinical benefits and specific subgroups, could be a reasonable alternative. The clinical effectiveness and cost-effectiveness of CAAS vFFR are uncertain. Randomised controlled trial evidence evaluating the effect of quantitative flow ratio on clinical and patient-centred outcomes is needed.
Future work
Studies are required to assess the diagnostic accuracy and clinical feasibility of CAAS vFFR. Large ongoing randomised trials will hopefully inform the clinical value of QAngio XA 3D/QFR.
Study registration
This study is registered as PROSPERO CRD42019154575.
Funding
This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in
Health Technology Assessment
; Vol. 25, No. 56. See the NIHR Journals Library website for further project information.
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