55,366 research outputs found
Guselkumab in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Study
No full textBackground & Aims: The QUASAR Phase 2b Induction Study evaluated the efficacy and safety of guselkumab, an interleukin-23p19 subunit antagonist, in patients with moderately to severely active ulcerative colitis (UC) with prior inadequate response and/or intolerance to corticosteroids, immunosuppressants, and/or advanced therapy. Methods: In this double-blind, placebo-controlled, dose-ranging, induction study, patients were randomized (1:1:1) to receive intravenous guselkumab 200 or 400 mg or placebo at weeks 0/4/8. The primary endpoint was clinical response (compared with baseline, modified Mayo score decrease ≥30% and ≥2 points, rectal bleeding subscore ≥1-point decrease or subscore of 0/1) at week 12. Guselkumab and placebo week-12 clinical nonresponders received subcutaneous or intravenous guselkumab 200 mg, respectively, at weeks 12/16/20 (uncontrolled study period). Results: The primary analysis population included patients with baseline modified Mayo scores ≥5 and ≤9 (intravenous guselkumab 200 mg, n = 101; 400 mg, n = 107; placebo, n = 105). Week-12 clinical response percentage was greater with guselkumab 200 mg (61.4%) and 400 mg (60.7%) vs placebo (27.6%; both P <. 001). Greater proportions of guselkumab-treated vs placebo-treated patients achieved all major secondary endpoints (clinical remission, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, and endoscopic normalization) at week 12. Among guselkumab week-12 clinical nonresponders, 54.3% and 50.0% of patients in the 200- and 400-mg groups, respectively, achieved clinical response at week 24. Safety was similar among guselkumab and placebo groups. Conclusions: Guselkumab intravenous induction was effective vs placebo in patients with moderately to severely active UC. Guselkumab was safe, and efficacy and safety were similar between guselkumab dose groups. ClinicalTrials.gov number: NCT04033445
The UN-SUSTAINABLE Match in HCV Recipients. Evidences from the Italian D-MELD Study on Balancing Donor-Recipient Risk Factors
No full textThe UN-SUSTAINABLE Match in HCV Recipients. Evidences from the Italian D-MELD Study on Balancing Donor-Recipient Risk Factor
All repair and reconstruction. Techniques from the SANTI study group
No full textBackground: Combining an anterior cruciate ligament (ACL) reconstruction with an anterolateral ligament (ALL) reconstruction results in significant advantages including reduced graft rupture rates, a lower risk of reoperation for secondary meniscectomy, improved knee stability, and higher rates of return to preinjury levels of sport. Indications: The previously reported indications for combined ACL and ALL reconstruction are as follows: ACL reconstruction revision; high-grade pivot shift test; long-term ACL rupture; young patients; pivoting activities; concomitant medial meniscus repair, and, specifically, regarding the ALL repair, it must be an acute surgery (within 15 days from injury). Technique Description: Several modern techniques have been described to repair and reconstruct the ALL. This technical note details a number of these techniques performed by the Scientific Anterior Cruciate Ligament Network International (SANTI) Study Group. Results: First, we describe a combined ACL reconstruction and double-bundle ALL reconstruction using hamstring autograft. Secondly, we describe a single-bundle ALL reconstruction using gracilis autograft. Thirdly, we describe an ALL reconstruction technique using a knotless soft anchor, which provides shallow fixation and prevents tunnel convergence. Finally, we describe a technique for ALL repair. Conclusion: Several techniques have been described to repair and reconstruct the ALL, all offering significant advantages over an isolated ACL reconstruction. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication
Robust automated detection of microstructural white matter degeneration in Alzheimer’s disease using machine learning classification of multicenter DTI data
No full textDiffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer’s disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of multicenter acquisition. We included a sample of 137 patients with clinically probable AD (MMSE 20.6±5.3) and 143 healthy elderly controls, scanned in nine different scanners. For diagnostic classification we used the DTI indices fractional anisotropy (FA) and mean diffusivity (MD) and, for comparison, gray matter and white matter density maps from anatomical MRI. Data were classified using a Support Vector Machine (SVM) and a Naïve Bayes (NB) classifier. We used two cross-validation approaches, (i) test and training samples randomly drawn from the entire data set (pooled cross-validation) and (ii) data from each scanner as test set, and the data from the remaining scanners as training set (scanner-specific cross-validation). In the pooled cross-validation, SVM achieved an accuracy of 80% for FA and 83% for MD. Accuracies for NB were significantly lower, ranging between 68% and 75%. Removing variance components arising from scanners using principal component analysis did not significantly change the classification results for both classifiers. For the scanner-specific cross-validation, the classification accuracy was reduced for both SVM and NB. After mean correction, classification accuracy reached a level comparable to the results obtained from the pooled cross-validation. Our findings support the notion that machine learning classification allows robust classification of DTI data sets arising from multiple scanners, even if a new data set comes from a scanner that was not part of the training sample
Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer
No full textBackground
Selective cyclooxygenase inhibitors may retard the progression of cancer, but they
have enhanced thrombotic potential. We report on cardiovascular adverse events in
patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer.
Methods
All serious adverse events that were cardiovascular thrombotic events were reviewed
in 2434 patients with stage II or III colorectal cancer participating in a randomized,
placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative
tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated
prematurely owing to worldwide withdrawal of rofecoxib. To examine possible
persistent risks, we examined cardiovascular thrombotic events reported up to 24
months after the trial was closed.
Results
The median duration of active treatment was 7.4 months. The 1167 patients receiving
rofecoxib and the 1160 patients receiving placebo were well matched, with a median
follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months
(27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events,
16 occurred in the rofecoxib group during or within 14 days after the treatment
period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards
model; 95% confidence interval [CI], 1.03 to 6.86; P = 0.04). Analysis of the Antiplatelet
Trialists’ Collaboration end point (the combined incidence of death from
cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction;
and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative
risk of 1.60 (95% CI, 0.57 to 4.51; P = 0.37). Fourteen more cardiovascular thrombotic
events, six in the rofecoxib group, were reported within the 2 years after trial
closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94;
P = 0.24). Four patients in the rofecoxib group and two in the placebo group died
from thrombotic causes during or within 14 days after the treatment period, and
during the follow-up period, one patient in the rofecoxib group and five patients in
the placebo group died from cardiovascular causes.
Conclusions
Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular
events among patients with a median study treatment of 7.4 months’ duration.
(Current Controlled Trials number, ISRCTN98278138.
Evidence for the alignment of quasar radio polarizations with large quasar group axes
No full textpeer reviewedRecently, evidence has been presented for the polarization vectors from quasars to preferentially align with the axes of the large
quasar groups (LQG) to which they belong. This report was based on observations made at optical wavelengths for two large quasar
groups at redshift ~1.3. The correlation suggests that the spin axes of quasars preferentially align with their surrounding large-scale
structure that is assumed to be traced by the LQGs. Here, we consider a large sample of LQGs built from the Sloan Digital Sky
Survey DR7 quasar catalogue in the redshift range 1.0 - 1.8. For quasars embedded in this sample, we collected radio polarization
measurements with the goal to study possible correlations between quasar polarization vectors and the major axis of their host LQGs.
Assuming the radio polarization vector is perpendicular to the quasar spin axis, we found that the quasar spin axis is preferentially
parallel to the LQG major axis inside LQGs that have at least 20 members. This result independently supports the observations at
optical wavelengths. We additionally found that when the richness of an LQG decreases, the quasar spin axis becomes preferentially
perpendicular to the LQG major axis and that no correlation is detected for quasar groups with fewer than 10 members
Effectiveness of brief schema group therapy for borderline personality disorder symptoms : a randomized pilot study
No full textBackground and objectives Schema group therapy is a potentially cost-effective treatment for borderline personality disorder (BPD). We piloted the feasibility and effectiveness of a 20-session schema group therapy without individual therapy among psychiatric BPD outpatients in a randomized pilot study registered as a clinical trial (ISRCTN76381242). Methods Altogether 42 psychiatric outpatients diagnosed with BPD were randomized 2:1 to a 20-session weekly schema group therapy plus treatment as usual (TAU) (n = 28) vs. a control group with TAU alone (n = 14). The primary outcome was decline of BPD symptoms in the short Borderline Symptom List (BSL-23) score. Secondary outcomes were decline in symptoms of anxiety, depression, alcohol use, and improvement in functioning and schema modes. Two external experts evaluated validity of the intervention based on videotaped sessions. Results Overall, 23 schema group therapy patients (82%) and 12 controls (86%) completed their treatment. Treatment validity good or very good. However, no significant differences emerged in the primary outcome mean BSL-23 decline (6.95 [SE 5.91] in group schema therapy vs. 12.55 [4.85] in TAU) or in any of the secondary outcome measures. Limitations Despite randomization, the TAU subgroup had non-significantly higher baseline scores in most measures. Small sample size predisposing to type II errors; reliance on self-reported outcomes. Conclusions Schema group therapy was feasible for psychiatric outpatients with BPD. However, in this small pilot study we did not find it more effective than TAU. Effectiveness of this short intervention remains open.Peer reviewe
Pulse oximetry adoption and oxygen orders at paediatric admission over 7 years in Kenya: a multihospital retrospective cohort study
No full textObjectives To characterise adoption and explore specific clinical and patient factors that might influence pulse oximetry and oxygen use in low-income and middle-income countries (LMICs) over time; to highlight useful considerations for entities working on programmes to improve access to pulse oximetry and oxygen.
Design A multihospital retrospective cohort study.
Settings All admissions (n=132 737) to paediatric wards of 18 purposely selected public hospitals in Kenya that joined a Clinical Information Network (CIN) between March 2014 and December 2020.
Outcomes Pulse oximetry use and oxygen prescription on admission; we performed growth-curve modelling to investigate the association of patient factors with study outcomes over time while adjusting for hospital factors.
Results Overall, pulse oximetry was used in 48.8% (64 722/132 737) of all admission cases. Use rose on average with each month of participation in the CIN (OR: 1.11, 95% CI 1.05 to 1.18) but patterns of adoption were highly variable across hospitals suggesting important factors at hospital level influence use of pulse oximetry. Of those with pulse oximetry measurement, 7% (4510/64 722) had hypoxaemia (SpO2 <90%). Across the same period, 8.6% (11 428/132 737) had oxygen prescribed but in 87%, pulse oximetry was either not done or the hypoxaemia threshold (SpO2 <90%) was not met. Lower chest-wall indrawing and other respiratory symptoms were associated with pulse oximetry use at admission and were also associated with oxygen prescription in the absence of pulse oximetry or hypoxaemia.
Conclusion The adoption of pulse oximetry recommended in international guidelines for assessing children with severe illness has been slow and erratic, reflecting system and organisational weaknesses. Most oxygen orders at admission seem driven by clinical and situational factors other than the presence of hypoxaemia. Programmes aiming to implement pulse oximetry and oxygen systems will likely need a long-term vision to promote adoption, guideline development and adherence and continuously examine impact
a European multicenter comparative cohort study
No full textFunding Information: AR received personal fees from Maat Pharma, IML received personal fees from MSD, and Gilead. AA received personal fees from Lilly Foundation, and grants from Grifols and Fisher & Paykel. CEL received personal fees from Bayer, Merck, Aerogen, Biomérieux, ThermoFisher Brahms, and Carmat. SN received personal fees from MSD, Bio-Rad, BioMérieux, Gilead, Fisher and Paykel, and Pfizer. All other authors declare no competing interests. Funding Information: This study was supported in part by a grant from the French government through the « Programme Investissement d’Avenir» (I-SITE ULNE) managed by the Agence Nationale de la Recherche (coVAPid project). Prof. Ignacio Martin-Loeches has been supported by SFI (Science Foundation Ireland), Grant Number 20/COV/0038. The funders of the study had no role in the study design, data collection, analysis, or interpretation, writing of the report, or decision to submit for publication. Publisher Copyright: © 2022, The Author(s).Background: Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. Objectives: To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. Methods: This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. Results: A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53–7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88–5.46, p < 0.0001). In the whole study population, putative IPA was associated with significant increase in 28-day mortality rate, and length of ICU stay, compared with colonized patients, or those with no IPA or Aspergillus colonization. Conclusions: Overall, the incidence of putative IPA was low. Its incidence was significantly lower in patients with SARS-CoV-2 pneumonia than in those with influenza pneumonia. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693.publishersversionpublishe
The relationship between Gas and Galaxies
No full textWe have investigated the 2D 2-point correlation function, ƐAG, between low column density Lya absorbers and galaxies at a redshift z ~ 1 for the first time. 141 Lya absorbers between redshifts z = 0.68 → 1.51 over a total redshift path length of ∆z = 1.09 were collected from HST STIS E230M absorption spectra towards the quasars HE 1122-1648 (z = 2.4) and PKS 1127-145 (z = 1.187). The column density of the correlated Lya absorbers ranged from 13.18 ≤ log(_10) (N(_HI) (cm(^-2))) ≤ 17.42, with a median column density of log(_10) (N(_HI) (cm(^-2))) 13.99 ± 0.21. A total of 200 galaxy redshifts within the surrounding 6.8' x 5.7' field of view of both quasars were identified in a R magnitude limited survey (21.5 ≤ R(_vega) ≤ 24.5) using the FORS2 spectrograph at the VLT. An upper-limit of Ɛ(_AG) = 18.3 was found when 194 Lya absorber-galaxy pairs were binned in redshift space, in a bin of size ∆σ = 1.0, ∆π= 2.0 h(^-1_70) Mpc along the projected separation and line of sight distances respectively. The upper-limit in the cross-correlation was found to be 3.2σ lower than the central peak in the galaxy auto-correlation, Ɛ’(_GG), which was equal to 3.89 ± 0.65, and » 5σ lower than the galaxy auto-correlation that was measured by the 2dFGRS and VVDS investigations. Thus we measured clustering amongst galaxies to be significantly stronger than the clustering between low column density Lya absorbers and galaxies. We then used GIMIC, a high-resolution hydrodynamical simulation, to re-create the cross-correlation. When binned with ∆σ= 1.0, ∆π = 2.0 h(^-1_73)Mpc in redshift space the simulations were consistent with the observations. No significant correlation exists between galaxies and Lya absorbers with log(_10) (N(_HI) (cm(^-2)))= 13 - 17, and ƐAG had a peak of 2.65 ± 0.78 at a redshift z = 1.0. The simulated Ɛag was observed to only marginally increase when measured with absorbers of an increasing column density between log(_10) (N(_HI) (cm(^-2)))- 13 - 17. Likewise Ɛag increased by < lσ to 3.96 ± 1.21 when the cross-correlation was measured at z = 0.5. Hence in the models there is no significant evolution in Ɛag with redshift. Ɛ GG from the GIMIC simulation was 27.05 ± 4.06 at z = 1.0, so when plotted in redshift space Ɛgg was again significantly greater than the cross-correlation. Thus we reached a conclusion that the galaxies that inhabit the nodes and filaments of the dark matter cosmic web are embedded within, but not necessarily correlated with the low column density Lya absorbers (log(_10) (N(_HI) (cm(^-2)))< 17) that loosely trace this filamentary structure. Hence the Lya absorption fines in quasar spectra are predominantly caused by photons passing through this diffuse medium, and not because the sightline passes through a galaxy halo. In a small side study, 47 C IV and 18 O VI absorption lines located in the UVES spectra of quasars HE 1122-1648 and PKS 1127-145 were used to calculate the oxygen and carbon metallicity of the Lya absorbers. We found no evolution with redshift for either species. The mean carbon solar metallicity between 1.0 < z < 2.35 was [C/H]= (-0.05±0.34)z-1.24±0.58. There was a large scatter that varied from solar abundances to [C/H]-3.41(^+0.12_-0.09). The mean oxygen solar metallicity between 2.0 < z < 2.4 was [0/H]= (1.01 ± 1.54)z - 3.94 ± 3.35, again with a similar large scatter in the oxygen abundance. These results are similar to previous findings by Schaye et al. (2003) and Aguirre et al. (2008), who studying C IV and O VI lines from 19 quasars at similar redshifts also found no significant evolution in the metallicity. All of these results indicate that many of these metals must have been expelled into the IGM at higher redshift
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