Publications by authors named "Manisha Desai"

212 Publications

Novel application of a discrete time-to-event model for randomized oral immunotherapy clinical trials with repeat food challenges.

Stat Med 2021 May 6. Epub 2021 May 6.

Quantitative Sciences Unit, Division of Biomedical Informatics Research, Department of Medicine, Stanford University, Palo Alto, California, USA.

The evaluation of double-blind, placebo-controlled food challenges (DBPCFC) generally focuses on a participant passing a challenge at a predetermined dose, and does not consider the dose of reaction for those who fail or are censored due to study discontinuation. Further, a number of food allergy trials have incorporated multiple DBPCFCs throughout the duration of the study in order to evaluate changes in reaction over time including sustained unresponsiveness from treatment. Outcomes arising from these trials are commonly modeled using Chi-squared or Fisher's exact tests at each time point. We propose applying time-to-event methodology to food allergy trials in order to exploit the inherent granularity of challenge outcomes that additionally accommodates repeated DBPCFCs. Specifically, we consider dose-to-failure for each study challenge and extend the cumulative tolerated dose across challenges to result in a dose-time axis. A discrete time-to-event framework is applied to the dose-time outcome to assess the efficacy of treatment across the entire study period. We illustrate ideas with data from the Peanut Oral Immunotherapy Study: Safety, Efficacy and Discovery (POISED) trial, conducted at Stanford University, which evaluated the efficacy of oral immunotherapy on desensitization and sustained unresponsiveness in peanut allergic children and adults. We demonstrate the advantages of time-to-event approaches for assessing the efficacy of treatment over time and incorporating information for those who failed or were lost to follow up. Further, we introduce a dose-time outcome that is interpretable to clinicians and allows for examination of such outcomes over time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/sim.9019DOI Listing
May 2021

Methods for training collaborative biostatisticians.

J Clin Transl Sci 2020 Aug 4;5(1):e26. Epub 2020 Aug 4.

Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.

The emphasis on team science in clinical and translational research increases the importance of collaborative biostatisticians (CBs) in healthcare. Adequate training and development of CBs ensure appropriate conduct of robust and meaningful research and, therefore, should be considered as a high-priority focus for biostatistics groups. Comprehensive training enhances clinical and translational research by facilitating more productive and efficient collaborations. While many graduate programs in Biostatistics and Epidemiology include training in research collaboration, it is often limited in scope and duration. Therefore, additional training is often required once a CB is hired into a full-time position. This article presents a comprehensive CB training strategy that can be adapted to any collaborative biostatistics group. This strategy follows a roadmap of the biostatistics collaboration process, which is also presented. A TIE approach (Teach the necessary skills, monitor the Implementation of these skills, and Evaluate the proficiency of these skills) was developed to support the adoption of key principles. The training strategy also incorporates a "train the trainer" approach to enable CBs who have successfully completed training to train new staff or faculty.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/cts.2020.518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057395PMC
August 2020

A community-based, multi-level, multi-setting, multi-component intervention to reduce weight gain among low socioeconomic status Latinx children with overweight or obesity: The Stanford GOALS randomised controlled trial.

Lancet Diabetes Endocrinol 2021 Apr 29. Epub 2021 Apr 29.

Quantitative Sciences Unit, Stanford University, Stanford, CA, USA; Department of Medicine, Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA; Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.

Background: There are few long-term studies of interventions to reduce in low socioeconomic status children with overweight or obesity. The Stanford GOALS trial evaluated a 3-year, community-based, multi-level, multi-setting, multi-component (MMM) systems intervention, to reduce weight gain among low socioeconomic status, Latinx children with overweight or obesity.

Methods: We did a two-arm, parallel group, randomised, open-label, active placebo-controlled trial with masked assessment over 3 years. Families from low-income, primarily Latinx communities in Northern California, CA, USA, with 7-11-year-old children with overweight or obesity were randomly assigned to a MMM intervention or a Health Education (HE) comparison intervention. The MMM intervention included home environment changes and behavioural counselling, community after school team sports, and reports to primary health-care providers. The primary outcome was child BMI trajectory over three years. Secondary outcomes included one- and two-year changes in BMI. This trial is registered with ClinicalTrials.govNCT01642836.

Findings: Between July 13, 2012, and Oct 3, 2013, 241 families were recruited and randomly assigned to MMM (n=120) or HE (n=121). Children's mean age was 9·5 (SD 1·4) years, 134 (56%) were female and 107 (44%) were male, and 236 (98%) were Latinx. 238 (99%) children participated in year 1, 233 (97%) in year 2, and 227 (94%) in year 3 of follow-up assessments. In intention-to-treat analysis, over 3 years, the difference between intervention groups in BMI trajectory was not significant (mean adjusted difference -0·25 [95% CI -0·90 to 0·40] kg/m; Cohen's d=0.10; p=0·45). Children in the MMM intervention group gained less BMI over 1 year than did children in the HE intervention group (-0·73 [-1·07 to -0·39] kg/m, d=0.55); the same was true over 2 years (-0·63 [-1·13 to -0·14] kg/m; d =0.33). No differential adverse events were observed.

Interpretation: The MMM intervention did not reduce BMI gain versus HE over 3 years but the effects over 1 and 2 years in this rigorous trial show the promise of this systems intervention approach for reducing weight gain and cardiometabolic risk factors in low socioeconomic status communities.

Funding: US National Institutes of Health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-8587(21)00084-XDOI Listing
April 2021

Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial.

Nat Commun 2021 03 30;12(1):1967. Epub 2021 Mar 30.

Department of Medicine, Stanford University, Stanford, CA, USA.

Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial (NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively, and symptom duration did not differ significantly between groups (HR 0.94; 95% CI 0.64 to 1.39). Both Lambda and placebo were well-tolerated, though liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-22177-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009873PMC
March 2021

Immune Changes Beyond Th2 Pathways During Rapid Multifood Immunotherapy enabled with Omalizumab.

Allergy 2021 Mar 30. Epub 2021 Mar 30.

Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA, USA.

Background: Multifood Oral Immunotherapy (mOIT) with adjunctive anti-IgE (omalizumab, Xolair ) treatment affords safe, effective, and rapid desensitization to multiple foods, although the specific immune mechanisms mediating this desensitization remain to be fully elucidated.

Methods: Participants in our phase 2 mOIT trial (NCT02643862) received omalizumab from baseline to week 16 and mOIT from week 8 to week 36. We compared the immune profile of PBMCs and plasma taken at baseline, week 8 and week 36 using high-dimensional mass cytometry, component-resolved diagnostics, the indirect basophil activation test, and Luminex.

Results: We found (i) decreased frequency of IL4 peanut-reactive CD4 T cells and a marked downregulation of GPR15 expression and CXCR3 frequency among γδ and CD8 T cell subsets at week 8 during the initial, omalizumab-alone induction phase; (ii) significant upregulation of the skin-homing receptor CCR4 in peanut-reactive CD4 T and Th2 effector memory (EM) cells and of cutaneous lymphocyte-associated antigen (CLA) in peanut-reactive CD8 T and CD8 EM cells (iii) downregulation of CD86 expression among antigen-presenting cell subsets; and (iv) reduction in pro-inflammatory cytokines, notably IL-17, at week 36 post-OIT. We also observed significant attenuation of the Th2 phenotype post-OIT, defined by downregulation of IL-4 peanut-reactive T cells and OX40 in Th2EM cells, increased allergen component-specific IgG4/IgE ratio, and decreased allergen-driven activation of indirectly sensitized basophils.

Conclusions: This exploratory study provides novel comprehensive insight into the immune underpinnings of desensitization through omalizumab-facilitated mOIT. Moreover, this study provides encouraging results to support the complex immune changes that can be induced by OIT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/all.14833DOI Listing
March 2021

Establishing a Data Science Unit in an Academic Medical Center: An Illustrative Model.

Acad Med 2021 Mar 23. Epub 2021 Mar 23.

M. Desai is professor of medicine and of biomedical data science, section chief of biostatistics, Division of Biomedical Informatics Research, and director, Quantitative Sciences Unit, Stanford University School of Medicine, Palo Alto, California. M. Boulos is executive director, Quantitative Sciences Unit, Stanford University School of Medicine, Palo Alto, California. G. M. Pomann is statistical research scientist and director, Duke Biostatistics Epidemiology and Research Design Methods Core, Duke University School of Medicine, Durham, North Carolina. G. K. Steinberg is Bernard and Ronni Lacroute - William Randolph Hearst Professor in Neurosurgery and Neurosciences, and chair, Department of Neurosurgery, Stanford University School of Medicine, Stanford, California. F. M. Longo is George E. and Lucy Becker Professor and chair, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California. M. Leonard is Arline and Pete Harman Professor and chair, Department of Pediatrics, Stanford University School of Medicine, and Adalyn Jay Physician in Chief, Lucile Packard Children's Hospital Stanford, Stanford, California. T. Montine is Stanford Medicine Endowed Professor in Pathology and chair, Department of Pathology, Stanford University School of Medicine, Stanford, California. A. L. Blomkalns is Stanford Medicine Professor of Emergency Medicine and chair, Department of Emergency Medicine, Stanford University School of Medicine, Stanford, California. R. A. Harrington is Arthur L. Bloomfield Professor of Medicine and chair, Department of Medicine, Stanford University School of Medicine, Stanford, California.

The field of data science has great potential to address critical questions relevant for academic medical centers. Data science initiatives are consequently being established within academic medicine. At the cornerstone of such initiatives are scientists who practice data science. These scientists include biostatisticians, clinical informaticians, database and software developers, computational scientists, and computational biologists. Too often, however, those involved in the practice of data science are viewed by academic leadership as providing a noncomplex service to facilitate research and further the careers of other academic faculty. The authors contend that the success of data science initiatives relies heavily on the understanding that the practice of data science is a critical intellectual contribution to the overall science conducted at an academic medical center. Further, careful thought by academic leadership is needed for allocation of resources devoted to the practice of data science. At the Stanford University School of Medicine, the authors have developed an innovative model for a data science collaboratory based on 4 fundamental elements: an emphasis on collaboration over consultation; a subscription-based funding mechanism that reflects commitment by key partners; an investment in the career development of faculty who practice data science; and a strong educational component for data science members in team science and for clinical and translational investigators in data science. As data science becomes increasingly essential to learning health systems, centers that specialize in the practice of data science are a critical component of the research infrastructure and intellectual environment of academic medical centers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ACM.0000000000004079DOI Listing
March 2021

Air pollution exposure is linked with methylation of immunoregulatory genes, altered immune cell profiles, and increased blood pressure in children.

Sci Rep 2021 Feb 18;11(1):4067. Epub 2021 Feb 18.

Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, CA, 94305, USA.

Ambient air pollution exposure is associated with cardiovascular dysregulation and immune system alterations, yet no study has investigated both simultaneously in children. Understanding the multifaceted impacts may provide early clues for clinical intervention prior to actual disease presentation. We therefore determined the associations between exposure to multiple air pollutants and both immunological outcomes (methylation and protein expression of immune cell types associated with immune regulation) and cardiovascular outcomes (blood pressure) in a cohort of school-aged children (6-8 years; n = 221) living in a city with known elevated pollution levels. Exposure to fine particular matter (PM), carbon monoxide (CO), and ozone (O) was linked to altered methylation of most CpG sites for genes Foxp3, IL-4, IL-10 and IFN-g, all involved in immune regulation (e.g. higher PM exposure 1 month prior to the study visit was independently associated with methylation of the IL-4 CpG24 site (est = 0.16; P = 0.0095). Also, immune T helper cell types (Th1, Th2 and Th17) were associated with short-term exposure to PM, O and CO (e.g. Th1 cells associated with PM at 30 days: est = - 0.34, P < 0.0001). Both B cells (est = - 0.19) and CD4+ cells (est = 0.16) were associated with 1 day NO2 exposure (P ≤ 0.031), whereas CD4+ and CD8+ cells were associated with chronic exposure to PAH, NOx and/or NO (P ≤ 0.038 for all). Finally, diastolic BP (DBP) was inversely associated with long-term exposures to both CO and PAH, and both systolic and pulse pressure were associated with short-term NO and chronic NOx exposure. Our findings demonstrate links between air pollution exposure and methylation of immunoregulatory genes, immune cell profiles and blood pressure, suggesting that even at a young age, the immune and cardiovascular systems are negatively impacted by exposure to air pollution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-83577-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893154PMC
February 2021

Colorectal Cancer Incidence After Colonoscopy at Ages 45-49 or 50-54 Years.

Gastroenterology 2021 May 9;160(6):2018-2028.e13. Epub 2021 Feb 9.

Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California; Institute of Clinical Outcomes Research and Education, Woodside, California.

Background & Aims: Colorectal cancer (CRC) incidence at ages younger than 50 years is increasing, leading to proposals to lower the CRC screening initiation age to 45 years. Data on the effectiveness of CRC screening at ages 45-49 years are lacking.

Methods: We studied the association between undergoing colonoscopy at ages 45-49 or 50-54 years and CRC incidence in a retrospective population-based cohort study using Florida's linked Healthcare Cost and Utilization Project databases with mandated reporting from 2005 to 2017 and Cox models extended for time-varying exposure.

Results: Among 195,600 persons with and 2.6 million without exposure to colonoscopy at ages 45-49 years, 276 and 4844 developed CRC, resulting in CRC incidence rates of 20.8 (95% CI, 18.5-23.4) and 30.6 (95% CI, 29.8-31.5) per 100,000 person-years, respectively. Among 660,248 persons with and 2.4 million without exposure to colonoscopy at ages 50-54 years, 798 and 6757 developed CRC, resulting in CRC incidence rates of 19.0 (95% CI, 17.7-20.4) and 51.9 (95% CI, 50.7-53.1) per 100,000 person-years, respectively. The adjusted hazard ratios for incident CRC after undergoing compared with not undergoing colonoscopy were 0.50 (95% CI, 0.44-0.56) at ages 45-49 years and 0.32 (95% CI, 0.29-0.34) at ages 50-54 years. The results were similar for women and men (hazard ratio, 0.48; 95% CI, 0.40-0.57 and hazard ratio, 0.52; 95% CI, 0.43-0.62 at ages 45-49 years, and hazard ratio, 0.35; 95% CI, 0.31-0.39 and hazard ratio, 0.29; 95% CI, 0.26-0.32 at ages 50-54 years, respectively).

Conclusions: Colonoscopy at ages 45-49 or 50-54 years was associated with substantial decreases in subsequent CRC incidence. These findings can inform screening guidelines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2021.02.015DOI Listing
May 2021

Clinical trials in a COVID-19 pandemic: Shared infrastructure for continuous learning in a rapidly changing landscape.

Clin Trials 2021 Feb 3:1740774520988298. Epub 2021 Feb 3.

Quantitative Sciences Unit, Division of Biomedical Informatics Research, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.

Background: Clinical trials, conducted efficiently and with the utmost integrity, are a key component in identifying effective vaccines, therapies, and other interventions urgently needed to solve the COVID-19 crisis. Yet launching and implementing trials with the rigor necessary to produce convincing results is a complicated and time-consuming process. Balancing rigor and efficiency involves relying on designs that employ flexible features to respond to a fast-changing landscape, measuring valid endpoints that result in translational actions and disseminating findings in a timely manner. We describe the challenges involved in creating infrastructure with potential utility for shared learning.

Methods: We have established a shared infrastructure that borrows strength across multiple trials. The infrastructure includes an endpoint registry to aid in selecting appropriate endpoints, a registry to facilitate establishing a Data & Safety Monitoring Board, common data collection instruments, a COVID-19 dedicated design and analysis team, and a pragmatic platform protocol, among other elements.

Results: The authors have relied on the shared infrastructure for six clinical trials for which they serve as the Data Coordinating Center and have a design and analysis team comprising 15 members who are dedicated to COVID-19. The authors established a pragmatic platform to simultaneously investigate multiple treatments for the outpatient with adaptive features to add or drop treatment arms.

Conclusion: The shared infrastructure provides appealing opportunities to evaluate disease in a more robust manner with fewer resources and is especially valued during a pandemic where efficiency in time and resources is crucial. The most important element of the shared infrastructure is the pragmatic platform. While it may be the most challenging of the elements to establish, it may provide the greatest benefit to both patients and researchers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1740774520988298DOI Listing
February 2021

The ARREST Pneumonia Clinical Trial. Rationale and Design.

Ann Am Thorac Soc 2021 04;18(4):698-708

Pulmonary, Critical Care, Allergy and Sleep Medicine Program, University of California, San Francisco, San Francisco, California.

Patients hospitalized for pneumonia are at high risk for mortality. Effective therapies are therefore needed. Recent randomized clinical trials suggest that systemic steroids can reduce the length of hospital stays among patients hospitalized for pneumonia. Furthermore, preliminary findings from a feasibility study demonstrated that early treatment with a combination of an inhaled corticosteroid and a bronchodilator can improve oxygenation and reduce risk of respiratory failure in patients at risk of acute respiratory distress syndrome. Whether such a combination administered early is effective in reducing acute respiratory failure (ARF) among patients hospitalized with pneumonia is unknown. Here we describe the ARREST Pneumonia (Arrest Respiratory Failure due to Pneumonia) trial designed to address this question. ARREST Pneumonia is a two-arm, randomized, double-blinded, placebo-controlled trial designed to test the efficacy of a combination of an inhaled corticosteroid and a β-agonist compared with placebo for the prevention of ARF in hospitalized participants with severe pneumonia. The primary outcome is ARF within 7 days of randomization, defined as a composite endpoint of intubation and mechanical ventilation; need for high-flow nasal cannula oxygen therapy or noninvasive ventilation for >36 hours (each alone or combined); or death within 36 hours of being placed on respiratory support. The planned enrollment is 600 adult participants at 10 academic medical centers. In addition, we will measure selected plasma biomarkers to better understand mechanisms of action. The trial is funded by the U.S. National Heart Lung and Blood Institute.Clinical trial registered with www.clinicaltrials.gov (NCT04193878).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1513/AnnalsATS.202009-1115SDDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008996PMC
April 2021

The French Academy of Sciences: Deliberations related to the discovery of anaesthesia.

Anaesth Intensive Care 2020 Nov 7;48(3_suppl):48-56. Epub 2020 Dec 7.

School of Medicine, University of Massachusetts Medical School, Boston, Massachusetts, USA.

In the mid-19th century, the French Academy of Sciences was one of the oldest and most prominent scientific institutions in the world. Individuals seeking credit for the discovery of surgical anaesthesia contacted the French academy to achieve recognition from this prestigious body of scientists and to spread news of the discovery throughout continental Europe. The French Academy of Sciences was established under the reign of King Louis XIV in 1666 with the goal of supporting and advancing scientific research. Membership was limited to the most accomplished French scientists, who presented their research at weekly meetings and advised the French government on scientific matters. The academy began their deliberations on the discovery of anaesthesia in January 1847. Since anaesthesia had already been tested in the United States and Great Britain, the main contributions of the French academy deliberations included refining administration techniques and documenting the effects of anaesthesia on animals and humans. Recognition of surgical anaesthesia by the French Academy of Sciences and the swift adoption of its use in surgical practice throughout the country lent credibility to this new discovery and enabled the discipline of surgery to progress. Nevertheless, the academy was not able to solve the initial problem for which they may have been contacted-the dispute about which individual deserved credit for the discovery of anaesthesia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0310057X20971637DOI Listing
November 2020

Twitter-Based Social Support Added to Fitbit Self-Monitoring for Decreasing Sedentary Behavior: Protocol for a Randomized Controlled Pilot Trial With Female Patients From a Women's Heart Clinic.

JMIR Res Protoc 2020 Dec 4;9(12):e20926. Epub 2020 Dec 4.

Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, United States.

Background: Prolonged sitting is an independent risk behavior for the development of chronic disease. With most interventions focusing on physical activity and exercise, there is a separate need for investigation into innovative and accessible interventions to decrease sedentary behavior throughout the day. Twitter is a social media platform with application for health communications and fostering of social support for health behavior change.

Objective: This pilot study aims to test the feasibility, acceptability, and preliminary efficacy of delivering daily behavior change strategies within private Twitter groups to foster peer-to-peer support and decrease sedentary behavior throughout the day in women. The Twitter group was combined with a Fitbit for self-monitoring activity and compared to a Fitbit-only control group.

Methods: In a 2-group design, participants were randomized to a Twitter + Fitbit treatment group or a Fitbit-only control group. Participants were recruited via the Stanford Research Repository System, screened for eligibility, and then invited to an orientation session. After providing informed consent, they were randomized. All participants received 13 weeks of tailored weekly step goals and a Fitbit. The treatment group participants, placed in a private Twitter support group, received daily automated behavior change "tweets" informed by theory and regular automated encouragement via text to communicate with the group. Fitbit data were collected daily throughout the treatment and follow-up period. Web-based surveys and accelerometer data were collected at baseline, treatment end (13 weeks), and at 8.5 weeks after the treatment.

Results: The initial study design funding was obtained from the Women's Heart Clinic and the Stanford Clayman Institute. Funding to run this pilot study was received from the National Institutes of Health's National Heart, Lung, and Blood Institute under Award Number K01HL136702. All procedures were approved by Stanford University's Institutional Review Board, #32127 in 2018, prior to beginning data collection. Recruitment for this study was conducted in May 2019. Of the 858 people screened, 113 met the eligibility criteria, 68 came to an information session, and 45 consented to participate in this pilot study. One participant dropped out of the intervention, and complete follow-up data were obtained from 39 of the 45 participants (87% of the sample). Data were collected over 6 months from June to December 2019. Feasibility, acceptability, and preliminary efficacy results are being analyzed and will be reported in the winter of 2021.

Conclusions: This pilot study is assessing the feasibility, acceptability, and preliminary efficacy of delivering behavior change strategies in a Twitter social support group to decrease sedentary behavior in women. These findings will inform a larger evaluation. With an accessible, tailorable, and flexible platform, Twitter-delivered interventions offer potential for many treatment variations and titrations, thereby testing the effects of different behavior change strategies, peer-group makeups, and health behaviors of interest.

Trial Registration: ClinicalTrials.gov NCT02958189, https://clinicaltrials.gov/ct2/show/NCT02958189.

International Registered Report Identifier (irrid): DERR1-10.2196/20926.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/20926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748950PMC
December 2020

Laboratory-wide association study of survival with prostate cancer.

Cancer 2021 Apr 25;127(7):1102-1113. Epub 2020 Nov 25.

Department of Urology, Stanford University School of Medicine, Stanford, California.

Background: Estimates of overall patient health are essential to inform treatment decisions for patients diagnosed with cancer. The authors applied XWAS methods, herein referred to as "laboratory-wide association study (LWAS)", to evaluate associations between routinely collected laboratory tests and survival in veterans with prostate cancer.

Methods: The authors identified 133,878 patients who were diagnosed with prostate cancer between 2000 and 2013 in the Veterans Health Administration using any laboratory tests collected within 6 months of diagnosis (3,345,083 results). Using the LWAS framework, the false-discovery rate was used to test the association between multiple laboratory tests and survival, and these results were validated using training, testing, and validation cohorts.

Results: A total of 31 laboratory tests associated with survival met stringent LWAS criteria. LWAS confirmed markers of prostate cancer biology (prostate-specific antigen: hazard ratio [HR], 1.07 [95% confidence interval (95% CI), 1.06-1.08]; and alkaline phosphatase: HR, 1.22 [95% CI, 1.20-1.24]) as well laboratory tests of general health (eg, serum albumin: HR, 0.78 [95% CI, 0.76-0.80]; and creatinine: HR, 1.05 [95% CI, 1.03-1.07]) and inflammation (leukocyte count: HR, 1.23 [95% CI, 1.98-1.26]; and erythrocyte sedimentation rate: HR, 1.33 [95% CI, 1.09-1.61]). In addition, the authors derived and validated separate models for patients with localized and advanced disease, identifying 28 laboratory markers and 15 laboratory markers, respectively, in each cohort.

Conclusions: The authors identified routinely collected laboratory data associated with survival for patients with prostate cancer using LWAS methodologies, including markers of prostate cancer biology, overall health, and inflammation. Broadening consideration of determinants of survival beyond those related to cancer itself could help to inform the design of clinical trials and aid in shared decision making.

Lay Summary: This article examined routine laboratory tests associated with survival among veterans with prostate cancer. Using laboratory-wide association studies, the authors identified 31 laboratory tests associated with survival that can be used to inform the design of clinical trials and aid patients in shared decision making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.33341DOI Listing
April 2021

Evaluation of variation in insurance payor mix among heart transplant centers.

J Heart Lung Transplant 2021 Jan 30;40(1):65-68. Epub 2020 Sep 30.

Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.healun.2020.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034596PMC
January 2021

Barbara E. Waud, M.D. (1931-), an early woman clinician scientist and professor of anesthesiology at University of Massachusetts Medical School.

J Anesth Hist 2020 09 13;6(3):143-150. Epub 2020 Jul 13.

University of Massachusetts Medical School, Worcester, MA.

After the first successful public demonstration of modern anesthesia in 1846, most female anesthetists were nurses by trade since none were yet allowed to attend medical school to become physicians. The turn of the twentieth century, however, brought about greater opportunity for female physician-anesthetists. We explore the life and career of Barbara E. Waud (1931-), a pioneering woman physician and researcher in the field of anesthesiology. Waud chose to pursue a career in medicine at a time when most women did not even attend college, and for most of her training and practice, she was the only woman in her department. Personal interviews with Waud, her daughter, and her colleagues highlight her rebellious and resilient nature that helped her overcome the obstacles put forth by male colleagues, and the judgment she received from female acquaintances for being a working mother. Waud's impressive career of dedicated clinical practice and ground-breaking research spanned four decades and inspired generations of physicians.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.janh.2020.07.003DOI Listing
September 2020

Julia Gordon Arrowood (1900 - 1984): A Brilliant Anesthesiologist and a Woman of Many Firsts in Medicine.

J Anesth Hist 2020 Sep 26;6(3):133-142. Epub 2020 Jun 26.

Department of Anesthesiology and Perioperative Care, University of Massachusetts Medical School, Worcester, Massachusetts.

After a brief "golden age" in the late 1800s, the patriarchal establishment fought back and women faced increasing restrictions in practicing medicine. In 1900, 18.2% of all physicians in the city of Boston were women, but this number decreased to 8.7% by 1930. The relatively young field of anesthesiology was one of the more welcoming specialties for women during this time. History has been unkind to these early female trailblazers who have often been overlooked in favor of the men in their fields. Julia Gordon Arrowood (1900-1984) was a forerunner for women in medicine and a prominent anesthesiologist in Boston from the 1930s until the 1950s. Her work included not only clinical medicine, but also research and teaching. She attended Boston University School of Medicine, graduating as valedictorian in the class of 1933. She interned at Belmont Hospital in Worcester, MA where she decided on a career in anesthesiology. She was accepted as a resident at Massachusetts General Hospital (MGH) by chief-anesthetist Henry Beecher in 1935, thereby becoming the first woman anesthesiology resident in Massachusetts. She remained at MGH and was named Acting Chief of Anesthesia in 1943. In 1944, she became president of the New England Society of Anesthesiologists, another first for a woman. In 1946, she joined Reginald Smithwick's team as Chief of Anesthesia at Massachusetts Memorial Hospital, Boston, and concurrently held the position of Professor of Anesthesiology at Boston University School of Medicine. Arrowood led many of the earliest studies on spinal anesthesia, muscle relaxants, and spinal headaches. In 1957, she moved to Kentucky and joined the United Mine Workers hospital system where she worked until her retirement in 1970. Women such as Julia Arrowood remain underrepresented in the annals of the history of medicine. Much work is needed to recognize the many contributions made by women physicians and to provide equal opportunities, pay, and status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.janh.2020.06.002DOI Listing
September 2020

The rise and fall of heterologous transfusion.

J Anesth Hist 2020 09 7;6(3):127-132. Epub 2020 Jul 7.

Department of Anesthesiology and Perioperative Medicine, University of Massachusetts Medical School, 55 North Lake Avenue, Worcester, MA 01655, United States. Electronic address:

Now a routine lifesaving treatment, blood transfusion between humans became a safe procedure only after many early therapeutic disasters. Performed between different species, heterologous transfusions actually succeeded homologous transfusions, those performed between members of the same species. In the early history of transfusion, both homologous and heterologous transfusions were performed in many clinical settings. Early clinicians were unable to distinguish between deaths caused by baseline illness and those resulting from transfusions. This report examines both early experiments with homologous transfusion between animals and later efforts investigating and finally abandoning heterologous transfusion. Topics explored include: 1) contributions and lessons learned from key individuals, 2) how these researchers suggested, performed, advocated, or challenged the practice of heterologous transfusion, and 3) why heterologous transfusions were even considered as a mode of therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.janh.2020.07.001DOI Listing
September 2020

Associations between 24 h Movement Behavior and Mental Health in Office Workers.

Int J Environ Res Public Health 2020 08 27;17(17). Epub 2020 Aug 27.

Department for Physical Activity and Health, The Swedish School of Sport and Health Sciences, 114 33 Stockholm, Sweden.

The associations between 24 h movement behavior, i.e., the way people distribute their time in different movement-related behaviors, on mental health are not well understood. This study applied a compositional data analysis approach to explore cross-sectional associations between device-measured moderate to vigorous physical activity (MVPA), light intensity physical activity (LIPA), sedentary behavior (SED), self-reported time in bed and mental health outcomes, i.e., depression or anxiety symptoms, burnout, mental wellbeing and stress, in office workers. ActiGraph accelerometers were worn for 24 h for at least 4 days to assess MVPA, LIPA, and SED. Sleep diaries were used in addition to identify time in bed. Analytic sample sizes for the different outcomes ranged from N = 345-370 participants. In this population of office workers with high levels of MVPA, the entire movement behavior composition was not associated to any of the mental health outcomes, but MVPA relative to all other behaviors was positively associated with mental wellbeing. This confirms the importance of MVPA for health relative to other movement-related behaviors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17176214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503924PMC
August 2020

Impact of cognitive behavioral therapy on depression symptoms after transcatheter aortic valve replacement: A randomized controlled trial.

Int J Cardiol 2020 Dec 13;321:61-68. Epub 2020 Aug 13.

Department of Medicine, Stanford University, United States of America.

Background: Depression is a significant concern after cardiac surgery and has not been studied in patients undergoing transcatheter aortic valve replacement (TAVR). We sought to examine the prevalence of pre-procedure depression and anxiety symptoms and explore whether brief bedside cognitive behavioral therapy (CBT) could prevent post-TAVR psychological distress.

Methods: We prospectively recruited consecutive TAVR patients and randomized them to receive brief CBT or treatment as usual (TAU) during their hospitalization. Multi-level regression techniques were used to evaluate changes by treatment arm in depression, anxiety, and quality of life from baseline to 1 month post-TAVR adjusted for sex, race, DM, CHF, MMSE, and STS score.

Results: One hundred and forty six participants were randomized. The mean age was 82 years, and 43% were female. Self-reported depression and anxiety scores meeting cutoffs for clinical level distress were 24.6% and 23.2% respectively. Both TAU and CBT groups had comparable improvements in depressive symptoms at 1-month (31% reduction for TAU and 35% reduction for CBT, p = .83). Similarly, both TAU and CBT groups had comparable improvements in anxiety symptoms at 1-month (8% reduction for TAU and 11% reduction for CBT, p = .1). Quality of life scores also improved and were not significantly different between the two groups.

Conclusions: Pre-procedure depression and anxiety may be common among patients undergoing TAVR. However, TAVR patients show spontaneous improvement in depression and anxiety scores at 1-month follow up, regardless of brief CBT. Further research is needed to determine whether more tailored CBT interventions may improve psychological and medical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2020.08.007DOI Listing
December 2020

Improving Clinical Outcomes in Newly Diagnosed Pediatric Type 1 Diabetes: Teamwork, Targets, Technology, and Tight Control-The 4T Study.

Front Endocrinol (Lausanne) 2020 9;11:360. Epub 2020 Jul 9.

Division of Endocrinology, Department of Pediatrics, Stanford University, Stanford, CA, United States.

Many youth with type 1 diabetes (T1D) do not achieve hemoglobin A1c (HbA1c) targets. The mean HbA1c of youth in the USA is higher than much of the developed world. Mean HbA1c in other nations has been successfully modified following benchmarking and quality improvement methods. In this review, we describe the novel 4T approach-teamwork, targets, technology, and tight control-to diabetes management in youth with new-onset T1D. In this program, the diabetes care team (physicians, nurse practitioners, certified diabetes educators, dieticians, social workers, psychologists, and exercise physiologists) work closely to deliver diabetes education from diagnosis. Part of the education curriculum involves early integration of technology, specifically continuous glucose monitoring (CGM), and developing a curriculum around using the CGM to maintain tight control and optimize quality of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2020.00360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363838PMC
July 2020

Life expectancy estimates for patients diagnosed with prostate cancer in the Veterans Health Administration.

Urol Oncol 2020 09 13;38(9):734.e1-734.e10. Epub 2020 Jul 13.

Department of Urology, Stanford University School of Medicine, Stanford, CA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA; Department of Medicine, Stanford University School of Medicine, Stanford, CA; VA Center for Innovation to Implementation, Palo Alto, CA. Electronic address:

Purpose: Accurate life expectancy estimates are required to inform prostate cancer treatment decisions. However, few models are specific to the population served or easily implemented in a clinical setting. We sought to create life expectancy estimates specific to Veterans diagnosed with prostate cancer.

Materials And Methods: Using national Veterans Health Administration electronic health records, we identified Veterans diagnosed with prostate cancer between 2000 and 2015. We abstracted demographics, comorbidities, oncologic staging, and treatment information. We fit Cox Proportional Hazards models to determine the impact of age, comorbidity, cancer risk, and race on survival. We stratified life expectancy estimates by age, comorbidity and cancer stage.

Results: Our analytic cohort included 145,678 patients. Survival modeling demonstrated the importance of age and comorbidity across all cancer risk categories. Life expectancy estimates generated from age and comorbidity data were predictive of overall survival (C-index 0.676, 95% CI 0.674-0.679) and visualized using Kaplan-Meier plots and heatmaps stratified by age and comorbidity. Separate life expectancy estimates were generated for patients with localized or advanced disease. These life expectancy estimates calibrate well across prostate cancer risk categories.

Conclusions: Life expectancy estimates are essential to providing patient-centered prostate cancer care. We developed accessible life expectancy estimation tools for Veterans diagnosed with prostate cancer that can be used in routine clinical practice to inform medical-decision making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urolonc.2020.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438257PMC
September 2020

The Origins, Evolution, and Spread of Anesthesia Monitoring Standards: From Boston to Across the World.

Anesth Analg 2021 03;132(3):890-898

From the Department of Anesthesiology, University of Massachusetts Medical School, Worcester, Massachusetts.

In the mid-1980s, the anesthesia departments at hospitals affiliated with Harvard Medical School were faced with a challenge: mounting medical malpractice costs. Malpractice insurance was provided by the Controlled Risk Insurance Company (CRICO), a patient safety and medical malpractice insurance company owned by and providing service to the Harvard medical community. CRICO spearheaded an effort to reduce these costs and ultimately found a way to decrease the risks associated with anesthesia. Here, we chronicle events that led to the dramatic changes in medical practice that resulted from the activities of a small group of concerned anesthesiologists at Harvard-affiliated hospitals. We place these events in a historical perspective and explore how other specialties followed this example, and end with current strategies that minimize the risk associated with anesthesia. We conducted interviews with principals who formulated original standards of patient monitoring. In addition, we consulted documents in the public domain and primary source material. Efforts of these pioneers resulted in the establishment of the seminal Harvard-based anesthesia monitoring standards for minimal monitoring. What followed was an unprecedented transformation of the entire field. After the implementation of these standards at Harvard-affiliated hospitals, the American Society of Anesthesiologists (ASA) adopted "Standards for Basic Anesthetic Monitoring" for use during the administration of all anesthetics in the United States. Other nations have since adopted similar guidelines and these practices have resulted in significant improvements in patient safety. Currently, we estimate mortality due to anesthesia in healthy patients to be 1:400,000-perhaps as much as 10 times lower since the early 1980s. What began as an attempt to lower medical malpractice costs in a group of university hospitals became a worldwide effort that resulted in improvements in patient safety. Other specialties have adopted similar measures. Currently, an attitude and appreciation of safety are exemplified by several practices that include among others-the adherence to these patient safety guidelines, simulator training, the promulgation of standards and guidelines by ASA, and the use of a safety checklist before induction of anesthesia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1213/ANE.0000000000005021DOI Listing
March 2021

Designing, Conducting, Monitoring, and Analyzing Data from Pragmatic Randomized Clinical Trials: Proceedings from a Multi-stakeholder Think Tank Meeting.

Ther Innov Regul Sci 2020 11 8;54(6):1477-1488. Epub 2020 Jun 8.

Abbvie, Chicago, IL, USA.

In late 2018, the Food and Drug Administration (FDA) outlined a framework for evaluating the possible use of real-world evidence (RWE) to support regulatory decision-making. This framework was created to facilitate studies that would generate high-quality RWE, including pragmatic clinical trials (PCTs), which are randomized trials designed to inform clinical or policy decisions by assessing the real-world effectiveness of an intervention. There is general agreement among experts that the use of existing healthcare and patient-generated data holds promise for making randomized trials more efficient, less costly, and more generalizable. Yet the benefits of relying on real-world data sources must be weighed against difficulties with ensuring data integrity and completeness. Additionally, appropriately monitoring patient safety in randomized trials of new drugs using healthcare system data that might not be available in real time can be quite difficult. Recognizing that these and other concerns are critical to the development and acceptability of PCTs, a group of stakeholders from academia, industry, professional organizations, regulatory bodies, government agencies, and patient advocates discussed a path forward for PCT growth and sustainability at a think tank meeting entitled "Monitoring and Analyzing Data from Pragmatic Streamlined Randomized Clinical Trials," which took place in January 2019 (Washington, DC). The goals of this meeting were to: (1) evaluate study design and methodological options specific to PCTs that have the potential to yield high-quality evidence; (2) discuss best practices to ensure data quality in PCTs; and (3) identify appropriate methods for study monitoring. Proceedings from the think tank meeting are summarized in this manuscript.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43441-020-00175-7DOI Listing
November 2020

Utility of Routine Surveillance Laboratory Testing in Detecting Relapse in Patients With Classic Hodgkin Lymphoma in First Remission: Results From a Large Single-Institution Study.

JCO Oncol Pract 2020 09 5;16(9):e902-e911. Epub 2020 May 5.

Department of Medicine, Stanford University, Stanford, CA.

Purpose: Classic Hodgkin lymphoma is highly curable with contemporary therapy. Although the limited role of surveillance imaging to detect early relapse for patients in complete remission at the end of therapy is well established, there is a paucity of data regarding role of laboratory testing in this setting.

Methods: Patients with newly diagnosed classic Hodgkin lymphoma uniformly treated with the Stanford V regimen from 1998-2014 and in complete remission for at least 3 months were identified in a single-center institutional database. Laboratory tests categorized by Common Terminology Criteria for Adverse Events v4.03 as grade 2 or higher were considered abnormal. Primary analysis included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of surveillance laboratory tests for predicting relapse in the first 3 years after end of treatment.

Results: Among 235 eligible patients, 24 (10.2%) patients ultimately relapsed. In the first 3 years after end of therapy, the mean number of surveillance blood draws per patient was 7.1, (range, 1-13). These 1,661 surveillance blood draws included 4,684 individual laboratory tests, comprising 1,609 CBCs, 1,578 metabolic panels, and 1,497 erythrocyte sedimentation rates. None of the biopsies confirming relapses were prompted by any abnormal laboratory finding. The sensitivity of any surveillance laboratory test for detecting relapse within 3 years of end of treatment was 72.7% (95% CI, 49.8% to 89.3%), specificity 22.6% (95% CI, 17.2% to 28.9%), yielding a PPV of 8.9% (95% CI, 7.0% to 11.3%) and NPV of 88.9% (95% CI, 79% to 94%).

Conclusion: Our study found limited clinically meaningful utility for routine surveillance laboratory testing in detecting relapse in patients with complete remission at end of treatment. Our results warrant consideration of modifications to current practice guidelines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JOP.19.00733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489479PMC
September 2020

A Smartwatch to Identify Atrial Fibrillation. Reply.

N Engl J Med 2020 03;382(10):975-976

Stanford University, Stanford, CA

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMc1916858DOI Listing
March 2020

Clinical and Economic Impact of Tailoring Screening to Predicted Colorectal Cancer Risk: A Decision Analytic Modeling Study.

Cancer Epidemiol Biomarkers Prev 2020 02 3;29(2):318-328. Epub 2019 Dec 3.

Department of Medicine, Stanford University School of Medicine, Stanford, California.

Background: Global increases in colorectal cancer risk have spurred debate about optimal use of screening resources. We explored the potential clinical and economic impact of colorectal cancer screening tailored to predicted colorectal cancer risk.

Methods: We compared screening tailored to predicted risk versus uniform screening in a validated decision analytic model, considering the average risk population's actual colorectal cancer risk distribution, and a risk-prediction tool's discriminatory ability and cost. Low, moderate, and high risk tiers were identified as colorectal cancer risk after age 50 years of ≤3%, >3 to <12%, and ≥12%, respectively, based on threshold analyses with willingness-to-pay <$50,000/quality-adjusted life-year (QALY) gained. Tailored colonoscopy (once at age 60 years for low risk, every 10 years for moderate risk, and every 5 years for high risk) was compared with colonoscopy every 10 years for all. Tailored fecal immunochemical testing (FIT)/colonoscopy (annual FIT for low and moderate risk, colonoscopy every 5 years for high risk) was compared with annual FIT for all.

Results: Assuming no colorectal cancer risk misclassification or risk-prediction tool costs, tailored screening was preferred over uniform screening. Tailored colonoscopy was minimally less effective than uniform colonoscopy, but saved $90,200-$889,000/QALY; tailored FIT/colonoscopy yielded more QALYs/person than annual FIT at $10,600-$60,000/QALY gained. Relatively modest colorectal cancer risk misclassification rates or risk-prediction tool costs resulted in uniform screening as the preferred approach.

Conclusions: Current risk-prediction tools may not yet be accurate enough to optimize colorectal cancer screening.

Impact: Uniform screening is likely to be preferred over tailored screening if a risk-prediction tool is associated with even modest misclassification rates or costs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-19-0949DOI Listing
February 2020

A double-blind, randomized, placebo-controlled pilot trial to evaluate safety and efficacy of vorapaxar on arteriovenous fistula maturation.

J Vasc Access 2020 Jul 27;21(4):467-474. Epub 2019 Nov 27.

Division of Vascular Surgery, School of Medicine, Stanford University, Stanford, CA, USA.

Background: Protease-activated receptor-1 antagonism by vorapaxar could facilitate arteriovenous fistula maturation but may increase bleeding risk.

Objective: The primary objective of the Vorapaxar Study for Maturation of arteriovenous fistula for Hemodialysis Access (VorapAccess) was to determine if vorapaxar improves arteriovenous fistula functional maturation in patients with end-stage renal disease.

Methods: VorapAccess was a randomized, placebo-controlled, double-blind pilot trial comparing 2.5 mg vorapaxar per day with placebo for twelve weeks starting on day two after arteriovenous fistula creation. The primary outcome was time to functional maturation defined as successful cannulation for six hemodialysis sessions within three weeks. The planned sample size was 50 participants. The study was terminated early after withdrawal of planned financial support. Given the small number of randomized patients, we performed descriptive analyses without inference testing.

Results: A total of 13 participants were randomly allocated study drug (six vorapaxar and seven placebo). The median age was 56 years and seven participants (54%) were female. The median (minimum-maximum) days to functional maturation were 169 (77-287) days in the vorapaxar group and 145 (48-198) days in the placebo group. Six of the 13 (46%) participants had arteriovenous fistula functional maturation within 180 days; two of six (33%) in the vorapaxar group and four of seven (57%) in the placebo group. There was one bleeding event in the placebo group.

Conclusion: Fewer than half of participants had functional maturation within 180 days after surgery, suggesting a major need for agents or strategies that enhance arteriovenous fistula maturation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1129729819887269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063544PMC
July 2020

Global metabolic profiling to model biological processes of aging in twins.

Aging Cell 2020 01 19;19(1):e13073. Epub 2019 Nov 19.

Department of Medicine, Sean N. Parker Center for Allergy and Asthma Research, Stanford University School of Medicine, Stanford, California.

Aging is intimately linked to system-wide metabolic changes that can be captured in blood. Understanding biological processes of aging in humans could help maintain a healthy aging trajectory and promote longevity. We performed untargeted plasma metabolomics quantifying 770 metabolites on a cross-sectional cohort of 268 healthy individuals including 125 twin pairs covering human lifespan (from 6 months to 82 years). Unsupervised clustering of metabolic profiles revealed 6 main aging trajectories throughout life that were associated with key metabolic pathways such as progestin steroids, xanthine metabolism, and long-chain fatty acids. A random forest (RF) model was successful to predict age in adult subjects (≥16 years) using 52 metabolites (R  = .97). Another RF model selected 54 metabolites to classify pediatric and adult participants (out-of-bag error = 8.58%). These RF models in combination with correlation network analysis were used to explore biological processes of healthy aging. The models highlighted established metabolites, like steroids, amino acids, and free fatty acids as well as novel metabolites and pathways. Finally, we show that metabolic profiles of twins become more dissimilar with age which provides insights into nongenetic age-related variability in metabolic profiles in response to environmental exposure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acel.13073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974708PMC
January 2020