scholarly journals Addressing guideline and policy changes during pragmatic clinical trials

2019 ◽  
Vol 16 (4) ◽  
pp. 431-437 ◽  
Author(s):  
Lesley H Curtis ◽  
Laura M Dember ◽  
Miguel A Vazquez ◽  
David Murray ◽  
Lynn DeBar ◽  
...  
Keyword(s):  
Public Health ◽  
Clinical Trials ◽  
Large Scale ◽  
Well Being ◽  
Clinical Equipoise ◽  
Opioid Use ◽  
Pragmatic Clinical Trials ◽  
The Face ◽  
Stage Renal Disease ◽  
End Stage

While conducting a set of large-scale multi-site pragmatic clinical trials involving high-impact public health issues such as end-stage renal disease, opioid use, and colorectal cancer, there were substantial changes to both policies and guidelines relevant to the trials. These external changes gave rise to unexpected challenges for the trials, including decisions regarding how to respond to new clinical practice guidelines, increased difficulty in implementing trial interventions, achieving separation between treatment groups, and differential responses across sites. In this article, we describe these challenges and the approaches used to address them. When deliberating appropriate action in the face of external changes during a pragmatic clinical trial, we recommend considering the well-being of the participants, clinical equipoise, and the strength and quality of the evidence associated with the change; involving those charged with data and safety monitoring; and where possible, planning for potential external changes as the trial is being designed. Any solution must balance the primary obligation to protect the well-being of participants with the secondary obligation to protect the integrity of the trial in order to gain meaningful answers to important public health questions.

Clinical trials in end-stage renal disease—priorities and challenges

2019 ◽  
Vol 34 (7) ◽  
pp. 1084-1089 ◽  
Author(s):  
Csaba P Kovesdy
Keyword(s):  
Clinical Trials ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Clinical Trial Design ◽  
Therapeutic Interventions ◽  
High Morbidity ◽  
Design Elements ◽  
Pragmatic Clinical Trials ◽  
Stage Renal Disease ◽  
End Stage

AbstractPatients with end-stage renal disease (ESRD) experience extremely high morbidity and mortality and there are virtually no therapeutic interventions besides dialysis treatment that are proven in properly designed randomized controlled trials (RCTs) to improve patients’ outcomes. Historically, the number of RCTs performed in the ESRD population has been very low compared with other medical subspecialties, and several of the few large RCTs have yielded inconclusive or negative results, dampening enthusiasm for future investment in similar trials. Recent initiatives promoting a focus on patient-centered outcomes and more active patient and caregiver involvement in the planning and conduct of clinical trials may result in more clinically relevant RCTs and broader participation from patients representing the diversity of the ESRD population. The adoption of novel clinical trial design elements characteristic of pragmatic clinical trials and platform trials could help improve both the internal and external validity of RCTs in ESRD, ultimately resulting in the adoption of therapeutic interventions that can be rapidly translated to clinical practice.

scholarly journals A therapeutic vascular conduit to support in vivo cell-secreted therapy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Edward X. Han ◽  
Hong Qian ◽  
Bo Jiang ◽  
Maria Figetakis ◽  
Natalia Kosyakova ◽  
...  
Keyword(s):  
Vascular Graft ◽  
Large Scale ◽  
Biological Effects ◽  
Therapeutic Protein ◽  
Close Proximity ◽  
Delivery Platform ◽  
Stage Renal Disease ◽  
End Stage

AbstractA significant barrier to implementation of cell-based therapies is providing adequate vascularization to provide oxygen and nutrients. Here we describe an approach for cell transplantation termed the Therapeutic Vascular Conduit (TVC), which uses an acellular vessel as a scaffold for a hydrogel sheath containing cells designed to secrete a therapeutic protein. The TVC can be directly anastomosed as a vascular graft. Modeling supports the concept that the TVC allows oxygenated blood to flow in close proximity to the transplanted cells to prevent hypoxia. As a proof-of-principle study, we used erythropoietin (EPO) as a model therapeutic protein. If implanted as an arteriovenous vascular graft, such a construct could serve a dual role as an EPO delivery platform and hemodialysis access for patients with end-stage renal disease. When implanted into nude rats, TVCs containing EPO-secreting fibroblasts were able to increase serum EPO and hemoglobin levels for up to 4 weeks. However, constitutive EPO expression resulted in macrophage infiltration and luminal obstruction of the TVC, thus limiting longer-term efficacy. Follow-up in vitro studies support the hypothesis that EPO also functions to recruit macrophages. The TVC is a promising approach to cell-based therapeutic delivery that has the potential to overcome the oxygenation barrier to large-scale cellular implantation and could thus be used for a myriad of clinical disorders. However, a complete understanding of the biological effects of the selected therapeutic is absolutely essential.

scholarly journals Approaches to Reducing Risk of COVID-19 Infections in Prisons and Immigration Detention Centers: A Commentary

2020 ◽  
pp. 073401682095770
Author(s):  
Kate Kelly ◽  
Nai Soto ◽  
Nadi Damond Wisseh ◽  
Shaina A. Clerget
Keyword(s):  
Public Health ◽  
Public Health Policy ◽  
Well Being ◽  
The United States ◽  
Correctional Staff ◽  
Staff Members ◽  
Detention Centers ◽  
Fast Spreading ◽  
Returning Home ◽  
The Face

Although often left out of public health efforts and policy decisions, prisons, jails, and detention centers are integral to community health. With an average of 650,000 citizens returning home from prison each year in the United States, and thousands of correctional staff members returning home every night, there are millions of touchpoints between outside communities and carceral settings. For this reason, carceral communities should be central to planning and policy making in response to the spread of the COVID-19 illness. As social workers and clinicians, we are urgently concerned that efforts to prevent COVID-19 infections in prisons are underdeveloped and inadequate in the face of a fast-spreading virus. In this commentary, we outline a set of public health, policy, and clinical recommendations based upon the existing literature to mitigate various risks to the well-being of carceral communities.

scholarly journals Demystifying the Opioid Trade in Anonymous Markets and Forums (Preprint)

2020 ◽  
Author(s):  
Zhengyi Li ◽  
Xiangyu Du ◽  
Xiaojing Liao ◽  
Xiaoqian Jiang ◽  
Tiffany Champagne-Langabeer
Keyword(s):  
Public Health ◽  
Supply Chain ◽  
Large Scale ◽  
Supply And Demand ◽  
Opioid Use Disorder ◽  
Public Health Issue ◽  
Opioid Use ◽  
Longitudinal Measurement ◽  
Online Marketplaces ◽  
Trading Activities

BACKGROUND Opioid use disorder presents a public health issue afflicting millions across the globe. There is a pressing need to understand the opioid supply chain to gain new insights into the mitigation of opioid use and effectively combat the opioid crisis. The role of anonymous online marketplaces and forums that resemble eBay or Amazon, where anyone can post, browse, and purchase opioid commodities, has become more and more important in opioid trading. Therefore, a greater understanding of anonymous markets and forums may enable public health officials and other stakeholders to comprehend the scope of the crisis. OBJECTIVE The objective of this work is to profile the opioid supply chain in anonymous markets and forums via a large-scale, longitudinal measurement study on anonymous market listings and posts. Toward this, we propose a series of techniques to collect data, to identify opioid jargon terms used in the anonymous marketplaces and forums, and to profile the opioid commodities, suppliers, and transactions. METHODS We first conducted a whole-site crawl of anonymous online marketplaces and forums to solicit data. Then, we developed a suite of opioid domain-specific text mining techniques (e.g., opioid jargon detection, opioid trading information retrieval) to recognize information relevant to opioid trading activities (e.g., commodities, price, shipping information, suppliers, etc.). After that, we conducted a comprehensive, large-scale, longitudinal study to demystify opioid trading activities in anonymous markets and forums. RESULTS A total of 248,359 listings from 10 anonymous online marketplaces and 1,138,961 traces (i.e., threads of posts) from 6 underground forums were collected. Among them, we identified 28,106 opioid product listings and 13,508 opioid-related promotional and review forum traces from 5147 unique opioid suppliers’ IDs and 2778 unique opioid buyers’ IDs. Our study characterized opioid suppliers (e.g., activeness and cross-market activities), commodities (e.g., popular items and their evolution), and transactions (e.g., origins and shipping destination) in anonymous marketplaces and forums, which enabled a greater understanding of the underground trading activities involved in international opioid supply and demand. CONCLUSIONS The results provide insight into opioid trading in the anonymous markets and forums, and may prove an effective mitigation data point for illuminating the opioid supply chain.

Marriage and End-Stage Renal Disease: Implications for African Americans

2010 ◽  
Vol 31 (9) ◽  
pp. 1230-1249
Author(s):  
Emily F. Shortridge ◽  
Cara V. James
Keyword(s):  
African Americans ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Well Being ◽  
Lifestyle Changes ◽  
Treatment Modalities ◽  
Dialysis Facilities ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

African Americans are disproportionately represented among patients with end-stage renal disease (ESRD). ESRD is managed with a strict routine that might include regular dialysis as well as dietary, fluid intake, and other lifestyle changes. In a disease such as this, with such disruptive treatment modalities, marriage, specifically, and its ties to well-being have the potential to significantly affect adherence to medical treatment and lifestyle recommendations as well as downstream health outcomes such as disease progression and mortality. The authors used data from the Dialysis Morbidity and Mortality Study, Wave 2, of the U.S. Renal Data System Database, a prospective study of 4,000 ESRD patients selected from a random sample of 25% U.S. dialysis facilities, to investigate these research questions. They found that married African American ESRD patients had marginally better outcomes on several clinical and psychosocial measures, which they hypothesize may be attributable to the instrumental and emotional support conferred by marriage.

Abstract MP30: Chronic Kidney Disease Progression and Risk of End-Stage Renal Disease: The Use of Change in Novel Kidney Filtration Markers

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Casey M Rebholz ◽  
Kunihiro Matsushita ◽  
Elizabeth Selvin ◽  
Morgan E Grams ◽  
Josef Coresh
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Trials ◽  
Kidney Disease ◽  
Cystatin C ◽  
End Stage Renal Disease ◽  
Ckd Progression ◽  
Percent Change ◽  
Stage Renal Disease ◽  
End Stage

Introduction: Chronic kidney disease (CKD) progression assessed by estimated GFR from creatinine (eGFR-Cr) is a risk factor for cardiovascular disease and end-stage renal disease (ESRD) and has been proposed as a surrogate endpoint for clinical trials. It is unclear if CKD progression assessed by change in different filtration markers has similar risk associations with ESRD. Hypothesis: We hypothesized that percent change in novel kidney filtration markers (β 2 -microglobulin and cystatin C) over a 6-year period would be independently associated with increased risk of ESRD during 15 years of follow-up, similar to the risk seen with change in eGFR-Cr. Methods: We conducted prospective analyses of the ARIC study (N=9,703). β 2 -microglobulin, cystatin C, and creatinine were measured at study visits 1 (1990-92) and 2 (1996-98). Incident ESRD (kidney dialysis or transplant) was defined as entry into the U.S. Renal Data System registry between study visit 2 and September 30, 2011. Cox proportional hazards regression was used to estimate the association between percent change in filtration marker and incident ESRD, adjusting for demographics, kidney disease risk factors, and 1 st measurement of the filtration marker. Results: During a median follow-up of 13.1 years, there were 142 incident ESRD cases. Median eGFR-Cr was 97.3 mL/min/1.73 m 2 at 1 st measurement and 89.0 mL/min/1.73 m 2 at 2 nd measurement. Percent change in eGFR-Cr was moderately correlated with percent change in the inverse of β 2 -microglobulin (r = 0.34) and the inverse of cystatin C (r = 0.36). Progression of CKD (10-25% and >25% decline in filtration function) was associated with increased ESRD risk, with novel markers (β 2 -microglobulin, cystatin C) showing an association at least as strong as the creatinine and eGFR-Cr estimates (Table). Conclusions: CKD progression assessed using novel filtration markers is independently associated with ESRD risk, suggesting the potential utility of measuring change in β 2 -microglobulin and cystatin C in clinical trials.

Peritoneal Dialysis in Japan: The Issue of Encapsulating Peritoneal Sclerosis and Future Challenges

2005 ◽  
Vol 25 (4_suppl) ◽  
pp. 77-82 ◽  
Author(s):  
Akira Saito
Keyword(s):  
Peritoneal Dialysis ◽  
Treatment Modalities ◽  
Bacterial Peritonitis ◽  
Abdominal Bleeding ◽  
Dialysis Solution ◽  
Future Challenges ◽  
The Face ◽  
Life Threatening ◽  
Stage Renal Disease ◽  
End Stage

Encapsulating peritoneal sclerosis (EPS) is a life-threatening complication of peritoneal dialysis (PD). The overall prevalence of EPS in Japanese PD patients is 2.3%. Among patients on PD for less than 5 years, the rate is 0.9%; among patients on PD for 5 – 10 years, the rate is 3.8%; and among patients on PD for >10 years, it is 11.5%. Thus, the longer the treatment duration, the higher the prevalence of EPS. Encapsulating peritoneal sclerosis does not result solely from the natural progression of peritoneal sclerosis. A “second hit” event, such as bacterial peritonitis, abdominal bleeding, or abdominal surgery may be needed to trigger the onset of EPS in the face of advanced peritoneal sclerosis. To prevent development of EPS, PD treatment is replaced by other treatments when patients reached high-transport status. Peritoneal lavage and prednisolone administration have been reported to be effective in preventing or stopping the progress of EPS. When bowel obstruction has occurred, total enterolysis to remove the fibrous capsule from the bowel is indicated. To maximize overall quality of life, patients with end-stage renal disease (ESRD) should have the choice to make use of all the treatment modalities available: PD, hemodialysis (HD), and transplantation. Furthermore, the development of truly biocompatible PD equipment—including peritoneal catheters, solutions, and systems—are desirable to extend PD treatment for the long term. The cost of individual products could decrease significantly if PD use were to increase to 30% from 10% among ESRD patients worldwide. As practitioners, we have to further improve the technical survival rate and functional duration of PD treatment so that adequate peritoneal function can be maintained for 10 years in at least 40% of PD patients. The goal is to place PD on par with HD using high-flux dialysis membranes and ultrapure dialysis solution.

Sense of meaning influences mental functioning in chronic renal patients

2018 ◽  
Vol 25 (12) ◽  
pp. 1978-1988 ◽  
Author(s):  
Luca Iani ◽  
Marco Lauriola ◽  
Andrea-René Angeramo ◽  
Elena Malinconico ◽  
Piero Porcelli
Keyword(s):  
Mental Health ◽  
Renal Disease ◽  
Physical Health ◽  
End Stage Renal Disease ◽  
Well Being ◽  
Physical Symptoms ◽  
Poor Mental Health ◽  
Spiritual Well Being ◽  
Stage Renal Disease ◽  
End Stage

In this preliminary study, we examined whether aspects of spiritual well-being accounted for mental and physical health-related quality of life in 68 patients with end-stage renal disease, when controlling for age, type of treatment, physical symptoms, and worries. Hierarchical multiple regressions showed that meaning was associated with better mental health, while worry and physical symptoms also accounted for poor mental health. Faith and peace did not contribute to mental health. Older age, type of treatment (hemodialysis), and physical symptoms accounted for poor physical health. Our findings suggest that clinicians should include spiritual well-being in future interventions for end-stage renal disease patients.

Sign in / Sign up

Export Citation Format

Share Document