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The treatment recommendation based on a network meta-analysis (NMA) is usually the single treatment with the highest expected value (EV) on an evaluative function. We explore approaches that recommend multiple treatments and that penalise uncertainty, making them suitable for risk-averse decision-makers. We introduce loss-adjusted EV (LaEV) and compare it to GRADE and three probability-based rankings. We define properties of a valid ranking under uncertainty and other desirable properties of ranking systems. A two-stage process is proposed: the first identifies treatments superior to the reference treatment; the second identifies those that are also within a minimal clinically important difference (MCID) of the best treatment. Decision rules and ranking systems are compared on stylised examples and 10 NMAs used in NICE (National Institute of Health and Care Excellence) guidelines. Only LaEV reliably delivers valid rankings under uncertainty and has all the desirable properties. In 10 NMAs comparing between 5 and 41 treatments, an EV decision maker would recommend 4–14 treatments, and LaEV 0–3 (median 2) fewer. GRADE rules give rise to anomalies, and, like the probability-based rankings, the number of treatments recommended depends on arbitrary probability cutoffs. Among treatments that are superior to the reference, GRADE privileges the more uncertain ones, and in 3/10 cases, GRADE failed to recommend the treatment with the highest EV and LaEV. A two-stage approach based on MCID ensures that EV- and LaEV-based rules recommend a clinically appropriate number of treatments. For a risk-averse decision maker, LaEV is conservative, simple to implement, and has an independent theoretical foundation.
Effect modification occurs when a covariate alters the relative effectiveness of treatment compared to control. It is widely understood that, when effect modification is present, treatment recommendations may vary by population and by subgroups within the population. Population-adjustment methods are increasingly used to adjust for differences in effect modifiers between study populations and to produce population-adjusted estimates in a relevant target population for decision-making. It is also widely understood that marginal and conditional estimands for non-collapsible effect measures, such as odds ratios or hazard ratios, do not in general coincide even without effect modification. However, the consequences of both non-collapsibility and effect modification together are little-discussed in the literature.
In this article, we set out the definitions of conditional and marginal estimands, illustrate their properties when effect modification is present, and discuss the implications for decision-making. In particular, we show that effect modification can result in conflicting treatment rankings between conditional and marginal estimates. This is because conditional and marginal estimands correspond to different decision questions that are no longer aligned when effect modification is present. For time-to-event outcomes, the presence of covariates implies that marginal hazard ratios are time-varying, and effect modification can cause marginal hazard curves to cross. We conclude with practical recommendations for decision-making in the presence of effect modification, based on pragmatic comparisons of both conditional and marginal estimates in the decision target population. Currently, multilevel network meta-regression is the only population-adjustment method capable of producing both conditional and marginal estimates, in any decision target population.
In 2013, 36 Ancestors of African descent were identified in an unmarked eighteenth-century burial ground during construction in Charleston, South Carolina. The site, later referred to as the Anson Street African Burial Ground, was buried beneath the growing city and forgotten in the centuries that followed. The ethical treatment of these ancestral remains was of paramount importance to our community. Historically, narratives relating to the lives of African descendant people in Charleston have been inadequately documented and shared. For these reasons, we engaged the local African American community in a multifaceted memorialization process. Together, we sought to sensitively ensure that the Ancestors’ identities and lives were fully explored according to the collective descendant community's wishes. To this end, we involved the community in researching and celebrating the Ancestors’ lives through arts and education programs and analyzed their and community members’ DNA to elucidate their ancestry. Our engagement initiatives increased access for all ages to archaeological, historical, and genetic research and encouraged active participation in the design of a permanent memorial. The Anson Street African Burial Ground Project provides a successful example of community-engaged activist archaeology focused on honoring the Ancestors and their descendants.
Background: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is an invasive intervention for patients with respiratory failure associated with COVID-19. This meta-analysis aims to determine the incidence of neurovascular complications in COVID-19 patients requiring VV-ECMO. Methods: Systematic literature search of MEDLINE, Embase, PsycINFO, and Cochrane databases was performed to identify studies that reported neurovascular complications of adult COVID-19 patients on VV-ECMO for respiratory failure. Case series and reports were excluded. Studies with 95% or more of its patients on VV-ECMO were pooled for meta-analysis. Results: Eighteen studies (n=1968) were included for meta-analyses. In COVID-19 patients requiring VV-ECMO, the incidences of intracranial hemorrhage and ischemic stroke were 11% [95% CI, 8–15%] and 2% [95% CI, 1–3%], respectively. Intraparenchymal and subarachnoid hemorrhages accounted for 73% and 8% of all intracranial hemorrhages, respectively. The risk ratio of mortality in COVID-19 patients with neurovascular complications on VV-ECMO compared to patients without neurovascular complications was 2.24 [95% CI, 1.46–3.46]. Conclusions: COVID-19 patients requiring VV-ECMO have a higher incidence of intracranial hemorrhage compared to historical data in non-COVID-19 patients (11% vs. 8%), while the incidence of ischemic stroke is similar (2%) in both cohorts. COVID-19 patients with neurovascular complications on VV-ECMO are at an increased risk of death.
Background: Women are reported to have worse outcomes than men following ischemic stroke despite similar treatment effects for thrombolysis and endovascular treatment. Methods: We performed a post-hoc analysis of patients with acute ischemic stroke and intracranial occlusion enrolled in INTERRSeCT, an international prospective cohort study. We compared workflow times, reperfusion therapy choices, and 90-day modified Rankin scale (mRS) scores. Results: We included 575 patients, mean age 70.2 years (SD: 13.1) and 48.5% female. There were no significant sex differences in onset-to-CT (males: 115 minutes [IQR: 72-171], females: 114 minutes [IQR: 75-196] ) or CT-to-thrombolysis time (males: 24 minutes [IQR: 17-32], females: 23 minutes [IQR: 18-36]). However, female participants had a 12-minute faster CT-to-groin-puncture time, p=0.001. Reperfusion therapies did not significantly differ by sex. Reperfusion therapies included thrombolysis alone (males: 46%, females: 49%), EVT alone (males: 34%, females: 34%), thrombolysis plus EVT (males: 8%, females 9%) and conservative management (males: 12%, females: 8%). Median 90-day mRS was 2 (IQR: 1-4) in both males and females, p=0.1. Conclusions: In the INTERRSeCT cohort, rates of reperfusion therapy, workflow times and 90-day outcomes were similar between sexes, suggesting that women are not subject to any poorer performance in key quality indicators for reperfusion treatment for acute stroke.
Pathological gambling is characterized in DSM IV-TR as one of the disorders of impulse control. Problem gambling is also part of what is considered behavioural addictions with intrusive thoughts about the game, are spending more and more important to play etc.
Objectives
There is no epidemiological study in France, that's why we make an epidemiological study on the prevalence of pathological gambling.
Methods
We wanted to study the prevalence of pathological gambling in a sample of 529 persons: 368 gamers of Pari Mutuel Urbain and La Française des Jeux, and 161 persons in the general population.
We used as instruments: SOGS for screening of pathological gambling, BIS-10 for impulsiveness's evaluation, HAD scale to assess anxiety and depression and ASRS for the evaluation of attention deficit disorder / hyperactivity disorder.
Results
The results show that the rate of pathological gambling in general population is 1.24% (this result is similar to those found in other countries such as Quebec)
Men are overrepresented in the group of pathological gamblers (88.9%), also with consumption of alcohol and tobacco. Depression and anxiety are particularly high, 40% of JPs with an anxiety score significantly higher.
Conclusions
It would be necessary to establish follow-up studies of populations and patients as well as specific studies on people who frequent casinos, racetracks and Internet gambling. Almost 20% of players have a gambling problem or risk and these people do not consult despite their psychological problems, family, work, debts…
Indirect comparisons via a common comparator (anchored comparisons) are commonly used in health technology assessment. However, common comparators may not be available, or the comparison may be biased due to differences in effect modifiers between the included studies. Recently proposed population adjustment methods aim to adjust for differences between study populations in the situation where individual patient data are available from at least one study, but not all studies. They can also be used when there is no common comparator or for single-arm studies (unanchored comparisons). We aim to characterise the use of population adjustment methods in technology appraisals (TAs) submitted to the United Kingdom National Institute for Health and Care Excellence (NICE).
Methods
We reviewed NICE TAs published between 01/01/2010 and 20/04/2018.
Results
Population adjustment methods were used in 7 percent (18/268) of TAs. Most applications used unanchored comparisons (89 percent, 16/18), and were in oncology (83 percent, 15/18). Methods used included matching-adjusted indirect comparisons (89 percent, 16/18) and simulated treatment comparisons (17 percent, 3/18). Covariates were included based on: availability, expert opinion, effective sample size, statistical significance, or cross-validation. Larger treatment networks were commonplace (56 percent, 10/18), but current methods cannot account for this. Appraisal committees received results of population-adjusted analyses with caution and typically looked for greater cost effectiveness to minimise decision risk.
Conclusions
Population adjustment methods are becoming increasingly common in NICE TAs, although their impact on decisions has been limited to date. Further research is needed to improve upon current methods, and to investigate their properties in simulation studies.
We evaluate the utility of the National Surveys of Attitudes and Sexual Lifestyles (Natsal) undertaken in 2000 and 2010, before and after the introduction of the National Chlamydia Screening Programme, as an evidence source for estimating the change in prevalence of Chlamydia trachomatis (CT) in England, Scotland and Wales. Both the 2000 and 2010 surveys tested urine samples for CT by Nucleic Acid Amplification Tests (NAATs). We examined the sources of uncertainty in estimates of CT prevalence change, including sample size and adjustments for test sensitivity and specificity, survey non-response and informative non-response. In 2000, the unadjusted CT prevalence was 4.22% in women aged 18–24 years; in 2010, CT prevalence was 3.92%, a non-significant absolute difference of 0.30 percentage points (95% credible interval −2.8 to 2.0). In addition to uncertainty due to small sample size, estimates were sensitive to specificity, survey non-response or informative non-response, such that plausible changes in any one of these would be enough to either reverse or double any likely change in prevalence. Alternative ways of monitoring changes in CT incidence and prevalence over time are discussed.
Pelvic inflammatory disease (PID) and more specifically salpingitis (visually confirmed inflammation) is the primary cause of tubal factor infertility and is an important risk factor for ectopic pregnancy. The risk of these outcomes increases following repeated episodes of PID. We developed a homogenous discrete-time Markov model for the distribution of PID history in the UK. We used a Bayesian framework to fully propagate parameter uncertainty into the model outputs. We estimated the model parameters from routine data, prospective studies, and other sources. We estimated that for women aged 35–44 years, 33·6% and 16·1% have experienced at least one episode of PID and salpingitis, respectively (diagnosed or not) and 10·7% have experienced one salpingitis and no further PID episodes, 3·7% one salpingitis and one further PID episode, and 1·7% one salpingitis and ⩾2 further PID episodes. Results are consistent with numerous external data sources, but not all. Studies of the proportion of PID that is diagnosed, and the proportion of PIDs that are salpingitis together with the severity distribution in different diagnostic settings and of overlap between routine data sources of PID would be valuable.
The Beck Depression Inventory, 2nd edition (BDI-II) is widely used in research on depression. However, the minimal clinically important difference (MCID) is unknown. MCID can be estimated in several ways. Here we take a patient-centred approach, anchoring the change on the BDI-II to the patient's global report of improvement.
Method
We used data collected (n = 1039) from three randomized controlled trials for the management of depression. Improvement on a ‘global rating of change’ question was compared with changes in BDI-II scores using general linear modelling to explore baseline dependency, assessing whether MCID is best measured in absolute terms (i.e. difference) or as percent reduction in scores from baseline (i.e. ratio), and receiver operator characteristics (ROC) to estimate MCID according to the optimal threshold above which individuals report feeling ‘better’.
Results
Improvement in BDI-II scores associated with reporting feeling ‘better’ depended on initial depression severity, and statistical modelling indicated that MCID is best measured on a ratio scale as a percentage reduction of score. We estimated a MCID of a 17.5% reduction in scores from baseline from ROC analyses. The corresponding estimate for individuals with longer duration depression who had not responded to antidepressants was higher at 32%.
Conclusions
MCID on the BDI-II is dependent on baseline severity, is best measured on a ratio scale, and the MCID for treatment-resistant depression is larger than that for more typical depression. This has important implications for clinical trials and practice.
A Diewert-flexible (dual) cost function was used to derive a system of conditional factor demand equations for Louisiana rice producers. Generalized Leontief cost and factor share equations were fitted for the 1955-87 period using Zellner's SURE system estimation procedure. The Aitken parameter estimates reveal that: (1) the optimal input mix of rice farmers varies with production scale, (2) the factor-augmenting technical change is labor and chemical saving but seed using, (3) pairwise input substitutions are limited, and (4) factor demands are own-price inelastic. An implication is that Louisiana rice farmers will not appreciably alter their factor utilizations when relative input prices change.
Information on the incidence of Chlamydia trachomatis (CT) is essential for models of the effectiveness and cost-effectiveness of screening programmes. We developed two independent estimates of CT incidence in women in England: one based on an incidence study, with estimates ‘recalibrated’ to the general population using data on setting-specific relative risks, and allowing for clearance and re-infection during follow-up; the second based on UK prevalence data, and information on the duration of CT infection. The consistency of independent sources of data on incidence, prevalence and duration, validates estimates of these parameters. Pooled estimates of the annual incidence rate in women aged 16–24 and 16–44 years for 2001–2005 using all these data were 0·05 [95% credible interval (CrI) 0·035–0·071] and 0·021 (95% CrI 0·015–0·028), respectively. Although, the estimates apply to England, similar methods could be used in other countries. The methods could be extended to dynamic models to synthesize, and assess the consistency of data on contact and transmission rates.
The Balloon-borne Large Aperture Submillimeter Telescope (BLAST) has recently conducted an extragalactic submillimetric survey of the Chandra Deep Field South region of unprecedented size, depth, and angular resolution in three wavebands centered at 250, 350, and 500 µm. BLAST wavelengths are chosen to study the Cosmic Infrared Background near its peak at 200 µm.We find that most of the CIB at these wavelengths is contributed by galaxies detected at 24 µm by the MIPS instrument on Spitzer, and that the source counts distribution shows a population with strongly evolving density and luminosity. These results anticipate what can be expected from the surveys that will be conducted with the SPIRE instrument on the Herschel space observatory.
Low weight at birth is a risk factor for increased mortality in infants undergoing surgery for congenitally malformed hearts. There has been a trend towards performing surgery in patients early, and for amenable lesions, in a single stage rather than following initial palliative procedures. Our goal was to report on the current incidences of morbidities and mortality in infants born with low weight and undergoing surgery for congenital cardiac disease.
Methods
We made a retrospective review of the data from patients meeting our criterions for entry from July, 2000, through July, 2004. The criterions for inclusion were weight at birth less than or equal to 2500 grams, and congenital cardiac malformations requiring surgery during the initial hospitalization. A criterion for exclusion was isolated persistent patency of the arterial duct. We assessed preoperative, intraoperative, and postoperative variables.
Results
We found a total of 105 patients meeting the criterions for inclusion. The median weight at birth was 2130 grams, and median gestational age was 36 weeks. The most common morbidity identified was infections of the blood stream. Infections, and chronic lung disease, were associated with increased length of stay. Survival overall was 76%. Patients with hypoplastic left heart syndrome, or a variant thereof, had the lowest survival, of 62%. The needs for cardiopulmonary resuscitation, or extracorporeal membrane oxygenation, post-operatively were the only factors identified as independent risk factors for mortality.
Conclusion
Patients undergoing surgery during infancy for congenital cardiac disease who are born with low weight have a higher mortality and morbidity than those born with normal weight.
A computer program was written to analyse oligonucleotide patterns displayed by gel electrophoresis following restriction endonuclease digestion of human cytomegaloviral DNA, and was applied to an epidemiological study of the transmission of infection in a hospital special care baby unit, with regard to infant-to-infant and mother-to-infant transmission.
The program calculates the molecular weight of oligonucleotides from their mobilities, using a cubic spline curve based on the mobilities of oligonucleotides from the AD169 strain. A matching algorithm then calculates the number of unmatched fragments for each pair of viral isolates. This was used as a similarity measure which successfully distinguished mother and infant isolate pairs from epidemiologically unrelated pairs.
The program is not intended to provide fully automatic matching, but could be recommended as a screening device to pick out pairs of strains which are sufficiently similar to suggest a common source of infection, and which may warrant closer comparison. Other applications are discussed, and the possible use of densitometers to automate data entry is considered.