Stereotactic body radiation therapy (SBRT) has been proposed for the palliation of painful vertebral bone metastases because higher radiation doses may result in superior and more durable pain ...control. A phase III clinical trial (Radiation Therapy Oncology Group 0631) comparing single fraction SBRT with single fraction external beam radiation therapy (EBRT) in palliative treatment of painful vertebral bone metastases is now ongoing. We performed a cost-effectiveness analysis to compare these strategies.
A Markov model, using a 1-month cycle over a lifetime horizon, was developed to compare the cost-effectiveness of SBRT (16 or 18 Gy in 1 fraction) with that of 8 Gy in 1 fraction of EBRT. Transition probabilities, quality of life utilities, and costs associated with SBRT and EBRT were captured in the model. Costs were based on Medicare reimbursement in 2014. Strategies were compared using the incremental cost-effectiveness ratio (ICER), and effectiveness was measured in quality-adjusted life years (QALYs). To account for uncertainty, 1-way, 2-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay (WTP) threshold of $100,000 per QALY gained.
Base case pain relief after the treatment was assumed as 20% higher in SBRT. Base case treatment costs for SBRT and EBRT were $9000 and $1087, respectively. In the base case analysis, SBRT resulted in an ICER of $124,552 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of the utility of unrelieved pain; the utility of relieved pain after initial treatment and median survival were also sensitive to variation. If median survival is ≥11 months, SBRT cost <$100,000 per QALY gained.
SBRT for palliation of vertebral bone metastases is not cost-effective compared with EBRT at a $100,000 per QALY gained WTP threshold. However, if median survival is ≥11 months, SBRT costs ≤$100,000 per QALY gained, suggesting that selective SBRT use in patients with longer expected survival may be the most cost-effective approach.
We report the discovery of eight gamma-ray pulsars in blind frequency searches using the LAT, onboard the Fermi Gamma-ray Space Telescope. Five of the eight pulsars are young (tau_c<100 kyr), ...energetic (Edot>10^36 erg/s), and located within the Galactic plane (|b|<3 deg). The remaining three are older, less energetic, and located off the plane. Five pulsars are associated with sources included in the LAT bright gamma-ray source list, but only one, PSR J1413-6205, is clearly associated with an EGRET source. PSR J1023-5746 has the smallest characteristic age (tau_c=4.6 kyr) and is the most energetic (Edot=1.1E37 erg/s) of all gamma-ray pulsars discovered so far in blind searches. PSRs J1957+5033 and J2055+25 have the largest characteristic ages (tau_c~1 Myr) and are the least energetic (Edot~5E33 erg/s) of the newly-discovered pulsars. We present the timing models, light curves, and detailed spectral parameters of the new pulsars. We used recent XMM observations to identify the counterpart of PSR J2055+25 as XMMU J205549.4+253959. In addition, publicly available archival Chandra X-ray data allowed us to identify the likely counterpart of PSR J1023-5746 as a faint, highly absorbed source, CXOU J102302.8-574606. The large X-ray absorption indicates that this could be among the most distant gamma-ray pulsars detected so far. PSR J1023-5746 is positionally coincident with the TeV source HESS J1023-575, located near the young stellar cluster Westerlund 2, while PSR J1954+2836 is coincident with a 4.3 sigma excess reported by Milagro at a median energy of 35 TeV. Deep radio follow-up observations of the eight pulsars resulted in no detections of pulsations and upper limits comparable to the faintest known radio pulsars, indicating that these can be included among the growing population of radio-quiet pulsars in our Galaxy being uncovered by the LAT, and currently numbering more than 20.
Abstract Introduction Little is known about patients' perceptions of electronic inhaler reminders, which have emerged in recent years as adherence promotion aids. This study explored asthma patients' ...attitudes toward the acceptability and utility of inhaler reminders. Methods Participants from a 6-month cluster randomized controlled trial who received reminders for missed doses via SmartTrack adherence monitors (Adherium Ltd) were interviewed to explore their perceptions; interviews were audio-recorded, transcribed and analysed thematically. Results 18 participants (50% male, mean age 39 years range 17–68) were interviewed. Three themes were identified. Acceptability and Feasibility : Interviewees found the monitor easy to use. For some, concerns about the monitor itself affected adherence, e.g. leaving it at home to avoid breakage. Positive features included that reminders played only for missed doses, and the choice of reminder tunes. Utility and Behavioural Impact : Interviewees described reminders as an effective "training" tool for adherence, encouraging habit-formation, behaviour change and attitude change. Reminders were considered less acceptable or useful by participants who preferred taking medication only when symptomatic or who doubted the necessity or safety of their medication. Sustainability : Some interviewees reported sustained behaviour change, supported by reminders, through the establishment of routine or via experiential learning that good adherence improved their asthma. Other interviewees wanted ongoing support (i.e. reminders or substitute adherence cues) after study end. Conclusion Patients with asthma found 6-months' use of reminders and adherence feedback acceptable and useful for improving their adherence attitudes, adherence behaviours and confidence in asthma self-management. Some patients may benefit from ongoing adherence support.
OPTN/SRTR 2018 Annual Data Report: Intestine Smith, J. M.; Weaver, T.; Skeans, M. A. ...
American journal of transplantation,
January 2020, 2020-01-00, 20200101, Letnik:
20, Številka:
s1
Journal Article
Recenzirano
Odprti dostop
Despite medical and surgical advances in treatment of intestinal failure, intestine transplant still plays an important role. However, the number of new patients added to the intestine transplant ...waiting list has decreased over the past decade, reaching a low of 135 in 2018. The number of intestine donors also decreased, reaching a low of 106 in 2018, and the number of intestine transplants performed declined to its lowest level, 104, of which 59% were intestine‐liver transplants. Graft failure has plateaued over the past decade. Patient survival for transplants in 2011‐2013 varied by age and transplant type. Patient survival was lowest for adult intestine‐liver recipients (1‐and 5‐year survival 66.7% and 49.1%, respectively) and highest for pediatric intestine recipients (1‐and 5‐year survival 89.1% and 76.4%, respectively).
ABSTRACT
We present 17 transit light curves of seven known warm-Jupiters observed with the CHaracterising ExOPlanet Satellite (CHEOPS). The light curves have been collected as part of the CHEOPS ...Guaranteed Time Observation (GTO) program that searches for transit-timing variation (TTV) of warm-Jupiters induced by a possible external perturber to shed light on the evolution path of such planetary systems. We describe the CHEOPS observation process, from the planning to the data analysis. In this work, we focused on the timing performance of CHEOPS, the impact of the sampling of the transit phases, and the improvement we can obtain by combining multiple transits together. We reached the highest precision on the transit time of about 13–16 s for the brightest target (WASP-38, G = 9.2) in our sample. From the combined analysis of multiple transits of fainter targets with G ≥ 11, we obtained a timing precision of ∼2 min. Additional observations with CHEOPS, covering a longer temporal baseline, will further improve the precision on the transit times and will allow us to detect possible TTV signals induced by an external perturber.
Wildfire refugia are forest patches that are minimally-impacted by fire and provide critical habitats for fire-sensitive species and seed sources for post-fire forest regeneration. Wildfire refugia ...are relatively understudied, particularly concerning the impacts of subsequent fires on existing refugia. We opportunistically re-visited 122 sites classified in 1994 for a prior fire refugia study, which were burned by two wildfires in 2012 in the Cascade mountains of central Washington, USA. We evaluated the fire effects for historically persistent fire refugia and compared them to the surrounding non-refugial forest matrix. Of 122 total refugial (43 plots) and non-refugial (79 plots) sites sampled following the 2012 wildfires, one refugial and five non-refugial plots did not burn in 2012. Refugial sites burned more severely and experienced higher tree mortality than non-refugial plots, potentially due to the greater amount of time since the last fire, producing higher fuel accumulation. Although most sites maintained the pre-fire development stage, 19 percent of sites transitioned to Early development and 31 percent of sites converted from Closed to Open canopy. These structural transitions may contribute to forest restoration in fire-adapted forests where fire has been excluded for over a century, but this requires further analysis.
ABSTRACT Objectives Inverse probability of treatment weighting (IPTW) has been used in observational studies to reduce selection bias. For estimates of the main effects to be obtained, a pseudo data ...set is created by weighting each subject by IPTW and analyzed with conventional regression models. Currently, variance estimation requires additional work depending on type of outcomes. Our goal is to demonstrate a statistical approach to directly obtain appropriate estimates of variance of the main effects in regression models. Methods We carried out theoretical and simulation studies to show that the variance of the main effects estimated directly from regressions using IPTW is underestimated and that the type I error rate is higher because of the inflated sample size in the pseudo data. The robust variance estimator using IPTW often slightly overestimates the variance of the main effects. We propose to use the stabilized weights to directly estimate both the main effect and its variance from conventional regression models. Results We applied the approach to a study examining the effectiveness of serum potassium monitoring in reducing hyperkalemia-associated adverse events among 27,355 diabetic patients newly prescribed with a renin-angiotensin-aldosterone system inhibitor. The incidence rate ratio (with monitoring vs. without monitoring) and confidence intervals were 0.46 (0.34, 0.61) using the stabilized weights compared with 0.46 (0.38, 0.55) using typical IPTW. Conclusions Our theoretical, simulation results and real data example demonstrate that the use of the stabilized weights in the pseudo data preserves the sample size of the original data, produces appropriate estimation of the variance of main effect, and maintains an appropriate type I error rate.
Studies have demonstrated that at least 20% of individuals infected with SARS-CoV-2 remain asymptomatic
. Although most global efforts have focused on severe illness in COVID-19, examining ...asymptomatic infection provides a unique opportunity to consider early immunological features that promote rapid viral clearance. Here, postulating that variation in the human leukocyte antigen (HLA) loci may underly processes mediating asymptomatic infection, we enrolled 29,947 individuals, for whom high-resolution HLA genotyping data were available, in a smartphone-based study designed to track COVID-19 symptoms and outcomes. Our discovery cohort (n = 1,428) comprised unvaccinated individuals who reported a positive test result for SARS-CoV-2. We tested for association of five HLA loci with disease course and identified a strong association between HLA-B*15:01 and asymptomatic infection, observed in two independent cohorts. Suggesting that this genetic association is due to pre-existing T cell immunity, we show that T cells from pre-pandemic samples from individuals carrying HLA-B*15:01 were reactive to the immunodominant SARS-CoV-2 S-derived peptide NQKLIANQF. The majority of the reactive T cells displayed a memory phenotype, were highly polyfunctional and were cross-reactive to a peptide derived from seasonal coronaviruses. The crystal structure of HLA-B*15:01-peptide complexes demonstrates that the peptides NQKLIANQF and NQKLIANAF (from OC43-CoV and HKU1-CoV) share a similar ability to be stabilized and presented by HLA-B*15:01. Finally, we show that the structural similarity of the peptides underpins T cell cross-reactivity of high-affinity public T cell receptors, providing the molecular basis for HLA-B*15:01-mediated pre-existing immunity.
Cognitive deficits persist in patients who survive traumatic brain injury (TBI). Lateral fluid percussion brain injury in the mouse, a model of human TBI, results in hippocampal-dependent cognitive ...impairment, similar to retrograde amnesia often associated with TBI. To identify potential substrates of the cognitive impairment, we evaluated regional neuronal loss, regional hippocampal excitability and inhibitory synaptic transmission. Design-based stereology demonstrated an approximate 40% loss of neurons through all subregions of the hippocampus following injury compared with sham. Input/output curves recorded in slices of injured brain demonstrated increased net synaptic efficacy in the dentate gyrus in concert with decreased net synaptic efficacy and excitatory postsynaptic potential-spike relationship in area CA1 compared with sham slices. Pharmacological agents modulating inhibitory transmission partially restored regional injury-induced alterations in net synaptic efficacy. Both evoked and spontaneous miniature inhibitory postsynaptic currents (mIPSCs) recorded in surviving dentate granule neurons were smaller and less frequent in injured brains than in uninjured brains. Conversely, both evoked and spontaneous mIPSCs recorded in surviving area CA1 pyramidal neurons were larger in injured brains than in uninjured brains. Together, these alterations suggest that regional hippocampal function is altered in the injured brain. This study demonstrates for the first time that brain injury selectively disrupts hippocampal function by causing uniform neuronal loss, inhibitory synaptic dysfunction, and regional, but opposing, shifts in circuit excitability. These changes may contribute to the cognitive impairments that result from brain injury.
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