Deconstructing the Kaplan-Meier curve: Quantification of treatment effect using the treatment effect process

In studies of survival and its association with treatment and other prognostic variables, elapsed time alone will often show itself to be among the strongest, if not the strongest, of the predictor variables. Kaplan-Meier curves will show the overall survival of each group and the general differences between groups due to treatment. However, the time-dependent nature of treatment effects is not always immediately transparent from these curves. More sophisticated tools are needed to spotlight the treatment effects. An important tool in this context is the treatment effect process. This tool can be potent in revealing the complex myriad of ways in which treatment can affect survival time. We look at a recently published study in which the outcome was relapse-free survival, and we illustrate how the use of the treatment effect process can provide a much deeper understanding of the relationship between time and treatment in this trial

Laser Cooling of Optically Trapped Molecules

Calcium monofluoride (CaF) molecules are loaded into an optical dipole trap (ODT) and subsequently laser cooled within the trap. Starting with magneto-optical trapping, we sub-Doppler cool CaF and then load $150(30)$ CaF molecules into an ODT. Enhanced loading by a factor of five is obtained when sub-Doppler cooling light and trapping light are on simultaneously. For trapped molecules, we directly observe efficient sub-Doppler cooling to a temperature of $60(5)$ $\mu\text{K}$. The trapped molecular density of $8(2)\times10^7$ cm$^{-3}$ is an order of magnitude greater than in the initial sub-Doppler cooled sample. The trap lifetime of 750(40) ms is dominated by background gas collisions.Comment: 5 pages, 5 figure

Confirming the Primarily Smooth Structure of the Vega Debris Disk at Millimeter Wavelengths

Clumpy structure in the debris disk around Vega has been previously reported at millimeter wavelengths and attributed to concentrations of dust grains trapped in resonances with an unseen planet. However, recent imaging at similar wavelengths with higher sensitivity has disputed the observed structure. We present three new millimeter wavelength observations that help to resolve the puzzling and contradictory observations. We have observed the Vega system with the Submillimeter Array (SMA) at a wavelength of 880 μm and an angular resolution of 5"; with the Combined Array for Research in Millimeter-wave Astronomy (CARMA) at a wavelength of 1.3 mm and an angular resolution of 5"; and with the Green Bank Telescope (GBT) at a wavelength of 3.3 mm and angular resolution of 10". Despite high sensitivity and short baselines, we do not detect the Vega debris disk in either of the interferometric data sets (SMA and CARMA), which should be sensitive at high significance to clumpy structure based on previously reported observations. We obtain a marginal (3σ) detection of disk emission in the GBT data; the spatial distribution of the emission is not well constrained.We analyze the observations in the context of several different models, demonstrating that the observations are consistent with a smooth, broad, axisymmetric disk with inner radius 20–100 AU and width ≾50 AU. The interferometric data require that at least half of the 860 μm emission detected by previous single-dish observations with the James Clerk Maxwell Telescope be distributed axisymmetrically, ruling out strong contributions from flux concentrations on spatial scales of ≾100 AU. These observations support recent results from the Plateau de Bure Interferometer indicating that previous detections of clumpy structure in the Vega debris disk were spurious

The nph2ph-transform: applications to the statistical analysis of completed clinical trials

We present several illustrations from completed clinical trials on a statistical approach that allows us to gain useful insights regarding the time dependency of treatment effects. Our approach leans on a simple proposition: all non-proportional hazards (NPH) models are equivalent to a proportional hazards model. The nph2ph transform brings an NPH model into a PH form. We often find very simple approximations for this transform, enabling us to analyze complex NPH observations as though they had arisen under proportional hazards. Many techniques become available to us, and we use these to understand treatment effects better

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Marine Ecoregion and Deepwater Horizon Oil Spill Affect Recruitment and Population Structure of a Salt Marsh Snail

Marine species with planktonic larvae often have high spatial and temporal variation in recruitment that leads to subsequent variation in the ecology of benthic adults. Using a combination of published and unpublished data, we compared the population structure of the salt marsh snail, Littoraria irrorata, between the South Atlantic Bight and the Gulf Coast of the United States to infer geographic differences in recruitment and to test the hypothesis that the Deepwater Horizon oil spill led to widespread recruitment failure of L. irrorata in Louisiana in 2010. Size-frequency distributions in both ecoregions were bimodal, with troughs in the distributions consistent with a transition from sub-adults to adults at ~13 mm in shell length as reported in the literature; however, adult snails reached larger sizes in the Gulf Coast. The ratio of sub-adults to adults was 1.5–2 times greater in the South Atlantic Bight than the Gulf Coast, consistent with higher recruitment rates in the South Atlantic Bight. Higher recruitment rates in the South Atlantic Bight could contribute to higher snail densities and reduced adult growth in this region. The ratio of sub-adults to adults in Louisiana was lower in 2011 than in previous years, and began to recover in 2012–2014, consistent with widespread recruitment failure in 2010, when large expanses of spilled oil were present in coastal waters. Our results reveal an important difference in the ecology of a key salt marsh invertebrate between the two ecoregions, and also suggest that the Deepwater Horizon oil spill may have caused widespread recruitment failure in this species and perhaps others with similar planktonic larval stages

Long-term prognosis for 1-year relapse-free survivors of CD34 cell-selected allogeneic hematopoietic stem cell transplantation : a landmark analysis

Altres ajuts: This research was supported in part by National Institutes of Health award number P01 CA23766 and NIH/NCI Cancer Center Support Grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.CD34 selection significantly improves GVHD-free survival in allogeneic hematopoietic cell transplantation (allo-HSCT). Specific information regarding long-term prognosis and risk factors for late mortality after CD34-selected allo-HSCT is lacking, however. We conducted a single-center landmark analysis in 276 patients alive without relapse 1 year after CD34-selected allo-HSCT for AML (n=164), ALL (n=33), or MDS (n=79). At 5 years' follow-up after the 1-year landmark (range 0.03-13 years), estimated RFS was 73% and OS 76%. The 5-year cumulative incidence of relapse and NRM were 11% and 16%, respectively. In multivariate analysis, HCT-CI score ≥ 3 correlated with marginally worse RFS (HR 1.78, 95% CI 0.97-3.28, p=0.06) and significantly worse OS (HR 2.53, 95% CI 1.26-5.08, p=0.004). Despite only 24% of patients with acute GVHD within 1 year, this also significantly correlated with worse RFS and OS, with increasing grades of acute GVHD associating with increasingly poorer survival on multivariate analysis (p<0.0001). Of 63 deaths after the landmark, GVHD accounted for 27% of deaths and was the most common cause of late mortality, followed by relapse and infection. While prognosis is excellent for patients alive without relapse 1 year after CD34-selected allo-HSCT, risks of late relapse and NRM persist, particularly due to GVHD

Quality of life at the end of life

<p>Abstract</p> <p>Background</p> <p>Little is known about self-perceived quality of life (QOL) near the end of life, because such information is difficult to collect and to interpret. Here, we describe QOL in the weeks near death and determine correlates of QOL over time, with emphasis on accounting for death and missing data.</p> <p>Methods</p> <p>Data on QOL were collected approximately every week in an ongoing randomized trial involving persons at the end of life. We used these data to describe QOL in the 52 weeks after enrollment in the trial (prospective analysis, N = 115), and also in the 10 weeks just prior to death (retrospective analysis, N = 83). The analysis consisted of graphs and regressions that accounted explicitly for death and imputed missing data.</p> <p>Results</p> <p>QOL was better than expected until the final 3 weeks of life, when a terminal drop was observed. Gender, race, education, cancer, and baseline health status were not significantly related to the number of “weeks of good-quality life” (WQL) during the study period. Persons younger than 60 had significantly higher WQL than older persons in the prospective analysis, but significantly lower WQL in the retrospective analysis. The retrospective results were somewhat sensitive to the imputation model.</p> <p>Conclusion</p> <p>In this exploratory study, QOL was better than expected in persons at the end of life, but special interventions may be needed for persons approaching a premature death, and also for the last 3 weeks of life. Our descriptions of the trajectory of QOL at the end of life may help other investigators to plan and analyze future studies of QOL. Methodology for dealing with death and the high amount of missing data in longitudinal studies at the end of life needs further investigation.</p

Durvalumab (MEDI 4736) in combination with extended neoadjuvant regimens in rectal cancer : a study protocol of a randomised phase II trial (PRIME-RT)

Acknowledgements We are grateful to Mr George Davidson and Ms Monica Jeffers for their input with writing the PRIME-RT protocol and patient information sheet. This study is co-sponsored by the University of Glasgow and NHS Greater Glasgow and Clyde. Funding PRIME-RT is funded by Astrazeneca and receives core funding from CRUK Clinical Trials Unit Glasgow for the purposes of trial set-up and data collection. The trial is co-sponsored by the University Of Glasgow and NHS Greater Glasgow and Clyde.Peer reviewedPublisher PD

Success of an International Learning Health Care System in Hematopoietic Cell Transplantation: The American Society of Blood and Marrow Transplantation Clinical Case Forum

The ASBMT Clinical Case Forum (CCF) was launched in 2014 as an online secure tool to enhance interaction and communication among hematopoietic cell transplantation (HCT) professionals worldwide through the discussion of challenging clinical care issues. After 14 months, we reviewed clinical and demographical data on cases posted in the CCF from 1/29/2014 to 3/18/2015. A total of 137 cases were posted during the study period. Ninety-two cases (67%) were allogeneic HCT, 29 (21%) autologous HCT and in 16 (12%) the type of transplant (auto vs. allo) was still under consideration. The diseases most frequently discussed included non-Hodgkin lymphoma (NHL; n = 30, 22%), acute myeloid leukemia (AML; n = 23, 17%) and multiple myeloma (MM; n = 20, 15%). When compared with the US transplant activity reported by the US Department of Health and Human Services, NHL and acute lymphoblastic leukemia cases were overrepresented in the CCF while myeloma was underrepresented (P < 0.001). A total of 259 topics were addressed in the CCF with a median of two topics/case (range 1-6). Particularly common topics included whether transplant was indicated (n = 57, 41%), conditioning regimen choice (n = 44, 32%), and post-HCT complications after day 100 (n = 43, 31%). The ASBMT CCF is a successful tool for collaborative discussion of complex cases in the HCT community worldwide and may allow identification of areas of controversy or unmet need from clinical, educational and research perspectives