925 research outputs found
Treatment Failure in Coeliac Disease: A Practical Guide to Investigation and Treatment of Non-responsive and Refractory Coeliac Disease
Abstract Coeliac disease is a common condition affecting up to 1% of the European adult population. Whilst the majority of patients will respond to a gluten free diet with resolution of symptoms and an improvement in histology, a significant minority have persistent problems. Refractory coeliac disease is a relatively uncommon cause of non-response to gluten free diet with potentially serious consequences of severe malabsorption and a high rate of progression to lymphoma. This review provides a practical guide to the investigation of patients who do not respond to a gluten free diet. We will highlight the differences between the more common non-responsive coeliac disease and the rare entity of refractory coeliac disease and discuss current management and treatment options for both non-responsive coeliac disease and refractory coeliac disease
A Thermo-Compositional Model of the African Cratonic Lithosphere
Recently, the continually increasing availability of seismic data has allowed high-resolution imaging of lithospheric structure beneath the African cratons. In this study, S-wave seismic tomography is combined with high resolution satellite gravity data in an integrated approach to investigate the structure of the cratonic lithosphere of Africa. A new model for the Moho depth and data on the crustal density structure is employed along with global dynamic models to calculate residual topography and mantle gravity residuals. Corrections for thermal effects of an initially juvenile mantle are estimated based on S-wave tomography and mineral physics. Joint inversion of the residuals yields necessary compositional adjustments that allow to recalculate the thermal effects. After several iterations, we obtain a consistent model of upper mantle temperature, thermal and compositional density variations, and Mg# as a measure of depletion, as well as an improved crustal density model. Our results show that thick and cold depleted lithosphere underlies West African, northern to central eastern Congo, and Zimbabwe Cratons. However, for most of these regions, the areal extent of their depleted lithosphere differs from the respective exposed Archean shields. Meanwhile, the lithosphere of Uganda, Tanzania, most of eastern and southern Congo, and the Kaapvaal Craton is thinner, warmer, and shows little or no depletion. Furthermore, the results allow to infer that the lithosphere of the exposed Archean shields of Congo and West African cratons was depleted before the single blocks were merged into their respective cratons
The paradox of verbal autopsy in cause of death assignment: symptom question unreliability but predictive accuracy
Background: We believe that it is important that governments understand the reliability of the mortality data which they have at their disposable to guide policy debates. In many instances, verbal autopsy (VA) will be the only source of mortality data for populations, yet little is known about how the accuracy of VA diagnoses is affected by the reliability of the symptom responses. We previously described the effect of the duration of time between death and VA administration on VA validity. In this paper, using the same dataset, we assess the relationship between the reliability and completeness of symptom responses and the reliability and accuracy of cause of death (COD) prediction. Methods: The study was based on VAs in the Population Health Metrics Research Consortium (PHMRC) VA Validation Dataset from study sites in Bohol and Manila, Philippines and Andhra Pradesh, India. The initial interview was repeated within 3-52 months of death. Question responses were assessed for reliability and completeness between the two survey rounds. COD was predicted by Tariff Method. Results: A sample of 4226 VAs was collected for 2113 decedents, including 1394 adults, 349 children, and 370 neonates. Mean question reliability was unexpectedly low (kappa = 0.447): 42.5 % of responses positive at the first interview were negative at the second, and 47.9 % of responses positive at the second had been negative at the first. Question reliability was greater for the short form of the PHMRC instrument (kappa = 0.497) and when analyzed at the level of the individual decedent (kappa = 0.610). Reliability at the level of the individual decedent was associated with COD predictive reliability and predictive accuracy. Conclusions: Families give coherent accounts of events leading to death but the details vary from interview to interview for the same case. Accounts are accurate but inconsistent; different subsets of symptoms are identified on each occasion. However, there are sufficient accurate and consistent subsets of symptoms to enable the Tariff Method to assign a COD. Questions which contributed most to COD prediction were also the most reliable and consistent across repeat interviews; these have been included in the short form VA questionnaire. Accuracy and reliability of diagnosis for an individual death depend on the quality of interview. This has considerable implications for the progressive roll out of VAs into civil registration and vital statistics (CRVS) systems
Real-Time Electronic Health Record Mortality Prediction During the COVID-19 Pandemic: A Prospective Cohort Study
Background: The SARS-CoV-2 virus has infected millions of people, overwhelming critical care resources in some regions. Many plans for rationing critical care resources during crises are based on the Sequential Organ Failure Assessment (SOFA) score. The COVID-19 pandemic created an emergent need to develop and validate a novel electronic health record (EHR)-computable tool to predict mortality.
Research Questions: To rapidly develop, validate, and implement a novel real-time mortality score for the COVID-19 pandemic that improves upon SOFA.
Study Design and Methods: We conducted a prospective cohort study of a regional health system with 12 hospitals in Colorado between March 2020 and July 2020. All patients >14 years old hospitalized during the study period without a do not resuscitate order were included. Patients were stratified by the diagnosis of COVID-19. From this cohort, we developed and validated a model using stacked generalization to predict mortality using data widely available in the EHR by combining five previously validated scores and additional novel variables reported to be associated with COVID-19-specific mortality. We compared the area under the receiver operator curve (AUROC) for the new model to the SOFA score and the Charlson Comorbidity Index.
Results: We prospectively analyzed 27,296 encounters, of which 1,358 (5.0%) were positive for SARS-CoV-2, 4,494 (16.5%) included intensive care unit (ICU)-level care, 1,480 (5.4%) included invasive mechanical ventilation, and 717 (2.6%) ended in death. The Charlson Comorbidity Index and SOFA scores predicted overall mortality with an AUROC of 0.72 and 0.90, respectively. Our novel score predicted overall mortality with AUROC 0.94. In the subset of patients with COVID-19, we predicted mortality with AUROC 0.90, whereas SOFA had AUROC of 0.85.
Interpretation: We developed and validated an accurate, in-hospital mortality prediction score in a live EHR for automatic and continuous calculation using a novel model, that improved upon SOFA.
Study Question: Can we improve upon the SOFA score for real-time mortality prediction during the COVID-19 pandemic by leveraging electronic health record (EHR) data?
Results: We rapidly developed and implemented a novel yet SOFA-anchored mortality model across 12 hospitals and conducted a prospective cohort study of 27,296 adult hospitalizations, 1,358 (5.0%) of which were positive for SARS-CoV-2. The Charlson Comorbidity Index and SOFA scores predicted all-cause mortality with AUROCs of 0.72 and 0.90, respectively. Our novel score predicted mortality with AUROC 0.94.
Interpretation: A novel EHR-based mortality score can be rapidly implemented to better predict patient outcomes during an evolving pandemic
Direct Observations of the Ionizing Star in the UC HII Region G29.96-0.02: A Strong Constraint on the Stellar Birth Line for Massive Stars
We have observed the ultracompact HII region G29.96-0.02 in the near infrared
J, H, and K bands and in the Br-gamma line. By comparison with radio
observations, we determine that the extinction to the nebula is AK = 2.14 with
a 3 sigma uncertainty of 0.25. We identify the ionizing star and determine its
intrinsic K magnitude. The star does not have an infrared excess and so appears
to be no longer accreting. The K magnitude and the bolometric luminosity allow
us to place limits on the location of the ionizing star in the HR diagram. The
3 sigma upper limit on the effective temperature of the ionizing star is 42500
K. We favor a luminosity appropriate for star with a mass in excess of about 60
solar masses. The limit on the temperature and luminosity exclude stars on the
ZAMS and stars within 10^6 yr of the ZAMS. Since the age of the UC HII region
is estimated to be only about 10^5 yr, we suggest that this is direct evidence
that the stellar birth line for massive stars at twice solar metallicity must
be significantly redder than the ZAMS.Comment: 42 pages; LaTex; 11 Postscript figures; accepted for publication in
Ap
The BLAST View of the Star Forming Region in Aquila (ell=45deg,b=0deg)
We have carried out the first general submillimeter analysis of the field
towards GRSMC 45.46+0.05, a massive star forming region in Aquila. The
deconvolved 6 deg^2 (3\degree X 2\degree) maps provided by BLAST in 2005 at
250, 350, and 500 micron were used to perform a preliminary characterization of
the clump population previously investigated in the infrared, radio, and
molecular maps. Interferometric CORNISH data at 4.8 GHz have also been used to
characterize the Ultracompact HII regions (UCHIIRs) within the main clumps. By
means of the BLAST maps we have produced an initial census of the submillimeter
structures that will be observed by Herschel, several of which are known
Infrared Dark Clouds (IRDCs). Our spectral energy distributions of the main
clumps in the field, located at ~7 kpc, reveal an active population with
temperatures of T~35-40 K and masses of ~10^3 Msun for a dust emissivity index
beta=1.5. The clump evolutionary stages range from evolved sources, with
extended HII regions and prominent IR stellar population, to massive young
stellar objects, prior to the formation of an UCHIIR.The CORNISH data have
revealed the details of the stellar content and structure of the UCHIIRs. In
most cases, the ionizing stars corresponding to the brightest radio detections
are capable of accounting for the clump bolometric luminosity, in most cases
powered by embedded OB stellar clusters
'Pre-endoscopy point of care test (Simtomax- IgA/IgG-Deamidated Gliadin Peptide) for coeliac disease in iron deficiency anaemia: diagnostic accuracy and a cost saving economic model'.
BACKGROUND: International guidelines recommend coeliac serology in iron deficiency anaemia, and duodenal biopsy for those tested positive to detect coeliac disease. However, pre-endoscopy serology is often unavailable, thus committing endoscopists to take routine duodenal biopsies. Some endoscopists consider duodenal biopsy mandatory in anaemia to exclude other pathologies. We hypothesise that using a point of care test at endoscopy could fill this gap, by providing rapid results to target anaemic patients who require biopsies, and save costs by biopsy avoidance. We therefore assessed three key aspects to this hypothesis: 1) the availability of pre-endoscopy serology in anaemia; 2) the sensitivities and cost effectiveness of pre-endoscopy coeliac screening with Simtomax in anaemia; 3) whether other anaemia-related pathologies could be missed by this targeted-biopsy approach. METHODS: Group 1: pre-endoscopy serology availability was retrospectively analysed in a multicentre cohort of 934 anaemic patients at 4 UK hospitals. Group 2: the sensitivities of Simtomax, endomysial and tissue-transglutaminase antibodies were compared in 133 prospectively recruited patients with iron deficiency anaemia attending for a gastroscopy. The sensitivities were measured against duodenal histology as the reference standard in all patients. The cost effectiveness of Simtomax was calculated based on the number of biopsies that could have been avoided compared to an all-biopsy approach. Group 3: the duodenal histology of 153 patients presenting to a separate iron deficiency anaemia clinic were retrospectively reviewed. RESULTS: In group 1, serology was available in 361 (33.8 %) patients. In group 2, the sensitivity and negative predictive value (NPV) were 100 % and 100 % for Simtomax, 96.2 % and 98.9 % for IgA-TTG, and 84.6 % and 96.4 % for EMA respectively. In group 3, the duodenal histology found no causes for anaemia other than coeliac disease. CONCLUSION: Simtomax had excellent diagnostic accuracy in iron deficiency anaemia and was comparable to conventional serology. Duodenal biopsy did not identify any causes other than coeliac disease for iron deficiency anaemia, suggesting that biopsy avoidance in Simtomax negative anaemic patients is unlikely to miss other anaemia-related pathologies. Due to its 100 % NPV, Simtomax could reduce unnecessary biopsies by 66 % if only those with a positive Simtomax were biopsied, potentially saving £3690/100 gastroscopies. TRIAL REGISTRATION: The group 2 study was retrospectively registered with clinicaltrials.gov. Trial registration date: 13(th) July 2016; TRIAL REGISTRATION NUMBER: NCT02834429
Clinical and Immunologic Features of Ultra-short Celiac Disease
BACKGROUND & AIMS: The clinical effects of gluten-sensitive
enteropathy with villous atrophy limited to the duodenal bulb
(D1) have not been delineated in adults with celiac disease. We
investigated the sensitivity of D1 biopsy analysis in the detection
of celiac disease, the number and sites of biopsies required
to detect ultra-short celiac disease (USCD, villous atrophy
limited to D1), and the clinical phenotype of USCD. METHODS:
We performed a prospective study of 1378 patients (mean age,
50.3 y; 62% female) who underwent endoscopy at a tertiary
medical center in the United Kingdom from 2008 through
2014; routine duodenal biopsy specimens were collected from
D1 and the second part of the duodenum (D2). Quadrantic D1
biopsy specimens were collected from 171 consecutive patients
with a high suspicion of celiac disease (mean age, 46.5 y; 64%
female). Clinical data from patients diagnosed with USCD, based
on biopsy analysis, were compared with those from patients
with conventional celiac disease (CCD) (villous atrophy beyond
D1) and individuals without celiac disease (controls). The
number of intraepithelial lymphocytes (IELs) and immune
phenotypes were compared between D1 vs D2 in patients with
celiac disease. RESULTS: Of the 1378 patients assessed, 268
(19.4%) were diagnosed with celiac disease; 9.7% of these
patients had villous atrophy confined to D1 (USCD; P < .0001).
Collection of a single additional biopsy specimen from any D1
site increased the sensitivity of celiac disease detection by
9.3%–10.8% (P < .0001). Patients with USCD were younger
(P ¼ .03), had lower titers of tissue transglutaminase antibody
(P ¼ .001), and less frequently presented with diarrhea
(P ¼ .001) than patients with CCD. Higher proportions of
patients with CCD had ferritin deficiency (P ¼ .007) or folate
deficiency (P ¼ .003) than patients with USCD or controls.
Patients with celiac disease had a median of 50 IELs/100
enterocytes in D1 and a median of 48 IELs/100 enterocytes
(P ¼ .7) in D2. The phenotype of IELs from patients with D1
celiac disease was indistinguishable from those of patients with
D2 celiac disease. CONCLUSIONS: Collection of a single
additional biopsy specimen from any site in the D1 intestine
increases the sensitivity of detection for celiac disease. Patients
with USCD may have early stage or limited celiac disease, with a
mild clinical phenotype and infrequent nutritional deficiencies
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