Summary
Background
Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome.
Aim
To create a prognostic model to estimate survival of patients with refractory ...coeliac disease.
Methods
We evaluated predictors of 5‐year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5‐year mortality.
Results
The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11–63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5‐year follow‐up (cumulative 5‐year all‐cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5‐year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38–3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22–6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61–0.85). A simple weighted three‐factor risk score was created to estimate 5‐year survival.
Conclusions
Using data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5‐year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow‐up.
Abstract
Background and Aims
The prognosis of lymphoma that occurs in patients with inflammatory bowel disease IBD is poorly known.
Methods
A multicentre retrospective cohort analysis was done in ...seven French tertiary centres from 1999 to 2019. Only lymphoma occurring in patients with previous established diagnosis of IBD were analysed. The primary outcome was progression-free survival at 3 years.
Results
A total of 52 patients male 65%, Crohn’s disease 79%, median age 48.3 years, median duration of IBD 10.1 years were included, of whom 37 had been previously exposed to immunosuppressants and/or biologics for at least 3 months and 20 had primary intestinal lymphomas. The lymphoma histological types were: diffuse large B cell lymphomas N = 17, Hodgkin lymphomas N = 17, indolent B cell lymphomas N = 12, and others including T cell lymphomas, mantle cell lymphomas, and unclassifiable B cell lymphoma N = 6. The median follow-up after lymphoma was 5.1 years (interquartile range IQR 4–7.8). Progression-free survival at 3 years was 85% in the overall population (95% confidence interval CI 75%–96%) with no significant difference between the exposed and unexposed group, 79% for patients exposed to immunosuppressants and/or biologics 95% CI 67%–94%, and 83% for patients diagnosed with primary intestinal lymphoma 95% CI 67%–100%. No relapse of IBD has been observed during chemotherapy. The IBD relapse rate at the end of the last chemotherapy cycle was 23% at 3 years 95% CI 11%-39% in the overall population.
Conclusions
In this large cohort, the prognosis for lymphomas occurring in IBD appears to be good and similar to what is expected, irrespective of the exposure to biologics and/or immunosuppressants.
We analyze high-resolution spectra obtained with the Space Telescope Imaging Spectrograph onboard the Hubble Space Telescope toward 34 nearby stars (< or =, slant 100 pc) to record Mg II, Fe II, and ...Mn II absorption due to the local interstellar medium (LISM). The heavy ions studied in this survey produce narrow absorption features that facilitate the identification of multiple interstellar components. We detected one to six individual absorption components along any given sight line, and the number of absorbers roughly correlates with the pathlength. The FUV spectra include many intrinsically broad absorption lines (i.e., of low atomic mass ions) and are often observed at medium resolution. Two stars in the sample that have circumstellar disks (49 Cet and HD141569) show evidence for absorption due to disk gas. We find that every prediction made by the Redfield & Linsky kinematic model of the LISM is confirmed by an observed component in the new lines of sight.
Although pain reduction is commonly the primary outcome in chronic pain clinical trials, physical functioning is also important. A challenge in designing chronic pain trials to determine efficacy and ...effectiveness of therapies is obtaining appropriate information about the impact of an intervention on physical function. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) and Outcome Measures in Rheumatology (OMERACT) convened a meeting to consider assessment of physical functioning and participation in research on chronic pain. The primary purpose of this article is to synthesize evidence on the scope of physical functioning to inform work on refining physical function outcome measurement. We address issues in assessing this broad construct and provide examples of frequently used measures of relevant concepts. Investigators can assess physical functioning using patient-reported outcome (PRO), performance-based, and objective measures of activity. This article aims to provide support for the use of these measures, covering broad aspects of functioning, including work participation, social participation, and caregiver burden, which researchers should consider when designing chronic pain clinical trials. Investigators should consider the inclusion of both PROs and performance-based measures as they provide different but also important complementary information. The development and use of reliable and valid PROs and performance-based measures of physical functioning may expedite development of treatments, and standardization of these measures has the potential to facilitate comparison across studies. We provide recommendations regarding important domains to stimulate research to develop tools that are more robust, address consistency and standardization, and engage patients early in tool development.
Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of ...preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.
A number of pharmacologic treatments examined in recent randomized clinical trials (RCTs) have failed to show statistically significant superiority to placebo in conditions in which their efficacy ...had previously been demonstrated. Assuming the validity of previous evidence of efficacy and the comparability of the patients and outcome measures in these studies, such results may be a consequence of limitations in the ability of these RCTs to demonstrate the benefits of efficacious analgesic treatments vs placebo ("assay sensitivity"). Efforts to improve the assay sensitivity of analgesic trials could reduce the rate of falsely negative trials of efficacious medications and improve the efficiency of analgesic drug development. Therefore, an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials consensus meeting was convened in which the assay sensitivity of chronic pain trials was reviewed and discussed. On the basis of this meeting and subsequent discussions, the authors recommend consideration of a number of patient, study design, study site, and outcome measurement factors that have the potential to affect the assay sensitivity of RCTs of chronic pain treatments. Increased attention to and research on methodological aspects of clinical trials and their relationships with assay sensitivity have the potential to provide the foundation for an evidence-based approach to the design of analgesic clinical trials and expedite the identification of analgesic treatments with improved efficacy and safety.
In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that ...patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are engaged as partners in research. Although this approach has become commonplace in some fields of clinical research, it remains the exception in clinical pain research. As such, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials convened a meeting with patient partners and international representatives from academia, patient advocacy groups, government regulatory agencies, research funding organizations, academic journals, and the biopharmaceutical industry to develop consensus recommendations for advancing patient engagement in all stages of clinical pain research in an effective and purposeful manner. This article summarizes the results of this meeting and offers considerations for meaningful and authentic engagement of patient partners in clinical pain research, including recommendations for representation, timing, continuous engagement, measurement, reporting, and research dissemination.
Understanding chronic inflammatory and neuropathic pain Hughes, Jane P.; Chessell, Iain; Malamut, Richard ...
Annals of the New York Academy of Sciences,
20/May , Letnik:
1255, Številka:
1
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
This meeting report highlights the main topics presented at the conference “Chronic Inflammatory and Neuropathic Pain,” convened jointly by the New York Academy of Sciences, MedImmune, and Grünenthal ...GmbH, on June 2–3, 2011, with the goal of providing a conducive environment for lively, informed, and synergistic conversation among participants from academia, industry, clinical practice, and government to explore new frontiers in our understanding and treatment of chronic and neuropathic pain. The program included leading and emerging investigators studying the pathophysiological mechanisms underlying neuropathic and chronic pain, and experts in the clinical development of pain therapies. Discussion included novel issues, current challenges, and future directions of basic research in pain and preclinical and clinical development of new therapies for chronic pain.
A method for improving the production of the radioisotope sup.123I in proton cyclotrons, which makes it possible to increase its technological yield by 2-3 times, is reported. For this purpose, it is ...proposed to introduce hydrogen into a target with sup.124Xe, which makes it possible to extract from it the sup.123I formed over the irradiation time on decay of the accumulated sup.123Xe.
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