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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).
We reviewed NICE TAs published between 01/01/2010 and 20/04/2018.
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.
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.
In the 1998-99 flight, BOOMERanG has produced maps of ∼4% of the sky at high Galactic latitudes, at frequencies of 90, 150, 240 and 410 GHz, with resolution ≳ 10'. The faint structure of the Cosmic Microwave Background at horizon and sub-horizon scales is evident in these maps. These maps compare well to the maps recently obtained at lower frequencies by the WMAP experiment. Here we compare the amplitude and morphology of the structures observed in the two sets of maps. We also outline the polarization sensitive version of BOOMERanG, which was flown early this year to measure the linear polarization of the microwave sky at 150, 240 and 350 GHz.
The Arcminute Cosmology Bolometer Array Receiver (Acbar) is a multifrequency millimeter-wave receiver optimized for observations of the Cosmic Microwave Background (CMB) and the Sunyaev-Zel'dovich (SZ) effect in clusters of galaxies. Acbar was installed on the 2.1 m Viper telescope at the South Pole in January 2001 and the results presented here incorporate data through July 2002. The power spectrum of the CMB at 150 GHz over the range ℓ = 150 — 3000 measured by Acbar is presented along with estimates for the values of the cosmological parameters within the context of ΛCDM models. The inclusion of ΩΛ greatly improves the fit to the power spectrum. Three-frequency images of the SZ decrement/increment are also presented for the galaxy cluster 1E0657–67.
The interpretation of 14C histograms is complicated by the non-linearity of the 14C time scale in terms of calendar years, which may result in clustering of 14C ages in certain time intervals unrelated to the (geologic or archaeologic) phenomenon of interest. One can calibrate 14C histograms for such distortions using two basic approaches. The KORHIS method constructs a 14C histogram before calibration is performed by means of a correction factor. We present the CALHIS method based on the Groningen calibration program for individual 14C ages. CALHIS first calibrates single 14C ages and then sums the resulting calibration distributions, thus yielding a calibrated 14C histogram. The individual calibration distributions are normalized to a standard Gaussian distribution before superposition, thus allowing direct comparison among various 14C histograms. Several experiments with test data sets demonstrate that CALHIS produces significantly better results than KORHIS. Although some problems remain (part of the distortions due to 14C variations cannot be eliminated), we show that CALHIS offers good prospects for using 14C histograms, particularly with highly precise and accurate 14C ages.
BOOMERanG has recently resolved structures on the last scattering surface at redshift ˜ 1100 with high signal to noise ratio. We review the technical advances which made this possible, and we focus on the current results for maps and power spectra, with special attention to the determination of the total mass-energy density in the Universe and of other cosmological parameters.
We show how estimates of parameters characterizing inflation-based theories of structure formation localized over the past year when large scale structure (LSS) information from galaxy and cluster surveys was combined with the rapidly developing cosmic microwave background (CMB) data, especially from the recent Boomerang and Maxima balloon experiments. All current CMB data plus a relatively weak prior probability on the Hubble constant, age and LSS points to little mean curvature (Ωtot = 1.08±0.06) and nearly scale invariant initial fluctuations (ns = 1.03±0.08), both predictions of (non-baroque) inflation theory. We emphasize the role that degeneracy among parameters in the Lpk = 212 ± 7 position of the (first acoustic) peak plays in defining the Ωtot range upon marginalization over other variables. Though the CDM density is in the expected range (Ωcdmh2 = 0.17 ± 0.02), the baryon density Ωbh2 = 0.030 ± 0.005 is somewhat above the independent 0.019 ± 0.002 nucleosynthesis estimates. CMB+LSS gives independent evidence for dark energy (ΩΛ = 0.66 ± 0.06) at the same level as from supernova (SN1) observations, with a phenomenological quintessence equation of state limited by SN1+CMB+LSS to wQ < −0.7 cf. the wQ=−1 cosmological constant case.
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.
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’.
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%.
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.
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.
Near Edge X-ray Absorption Fine Structure (NEXAFS) spectroscopy of polymers performed in a scanning transmission X-ray microscope (STXM) can provide chemical speciation with <0.1 gm spatial resolution in imaging mode. The core excitation spectra of molecular compounds that are structural analogues of polymers help interpret the NEXAFS spectra of polymers. The effect of nt-delocalization on polymer NEXAFS is discussed and illustrated by comparison to molecular spectra. Extended Htickel calculations are particularly useful for providing insight into the relationship between chemical structure and the molecular and polymer spectra. We report the interpretation of experimental NEXAFS spectra of polyethylene terephthalate (PET). Molecular models indicate that NEXAFS will be sensitive to structural isomerization in polyester polymers. We demonstrate the capability of NEXAFS to distinguish hard-segment and soft-segment phase segregation in polyurethanes.
We have begun a program to characterize magnetic alloy overlayers using both magnetic x-ray circular dichroism (MXCD) and magnetic x-ray linear dichroism (MXLD). This will allow a direct comparison of MXCD-absorption and MXLD-photoelectron emission. First results from the Advanced Light Source will be presented.
We have utilized the scanning transmission x-ray microscope at Brookhaven National Laboratory to acquire high energy resolution spectra of various polymers and to investigate the bulk characteristics of multiphasic polymeric materials with chemical sensitivity at a spatial resolution of about 50 nm. We present studies ranging from phase separated liquid crystalline polyesters and polyurethanes to various polymer blends. Improvements in the NEXAFS imaging and spectral acquisition protocol in the recent past provide much improved spectral fidelity and include in situ energy calibration with CO2.
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.
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.
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.
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.