The Trial Innovation Network Liaison Team: building a national clinical and translational community of practice.

In 2016, the National Center for Advancing Translational Science launched the Trial Innovation Network (TIN) to address barriers to efficient and informative multicenter trials. The TIN provides a national platform, working in partnership with 60+ Clinical and Translational Science Award (CTSA) hubs across the country to support the design and conduct of successful multicenter trials. A dedicated Hub Liaison Team (HLT) was established within each CTSA to facilitate connection between the hubs and the newly launched Trial and Recruitment Innovation Centers.

Leveraging the Expertise of the CTSA Program to Increase the Impact and Efficiency of Clinical Trials.

Importance: Multicenter clinical trials play a critical role in the translational processes that enable new treatments to reach all people and improve public health. However, conducting multicenter randomized clinical trials (mRCT) presents challenges. The Trial Innovation Network (TIN), established in 2016 to partner with the Clinical and Translational Science Award (CTSA) Consortium of academic medical institutions in the implementation of mRCTs, consists of 3 Trial Innovation Centers (TICs) and 1 Recruitment Innovation Center (RIC).

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Immune dysregulation contributes to poorer outcomes in COVID-19.

Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

Design, Setting, And Participants: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia.

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression.

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map.

Abatacept for Treatment of Adults Hospitalized with Moderate or Severe Covid-19.

Background: We investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19.

Methods: We conducted a master protocol to investigate immunomodulators for potential benefit treating patients hospitalized with Covid-19 and report results for abatacept. Intravenous abatacept (one-time dose 10 mg/kg, maximum dose 1000 mg) plus standard of care (SOC) was compared with shared placebo plus SOC.

Infliximab for Treatment of Adults Hospitalized with Moderate or Severe Covid-19.

Background: Immune dysregulation contributes to poorer outcomes in severe Covid-19. Immunomodulators targeting various pathways have improved outcomes. We investigated whether infliximab provides benefit over standard of care.

Empathy in Medical Education: Its Nature and Nurture - a Qualitative Study of the Views of Students and Tutors.

Context: Medical education is committed to teaching patient centred communication and empathy. However, quantitative research suggests empathy scores tend to decline as students progress through medical school. In qualitative terms, there is a need to better understand how students and tutors view the practice and teaching of clinical empathy and the phenomenon of empathic erosion.

NIH's Helping to End Addiction Long-term Initiative (NIH HEAL Initiative) Clinical Pain Management Common Data Element Program.

The Helping to End Addiction Long-term Initiative (NIH HEAL Initiative) is an aggressive trans-NIH effort to speed solutions to stem the national opioid public health crisis, including through improved pain management. Toward this end, the NIH HEAL Initiative launched a common data element (CDE) program to ensure that NIH-funded clinical pain research studies would collect data in a standardized way. NIH HEAL Initiative staff launched a process to determine which pain-related core domains should be assessed by every clinical pain study and what questionnaires are required to ensure that the data is collected uniformly.

Platypnoea and orthodeoxia in the hepatopulmonary syndrome.

A 71-year-old female patient with alcohol-induced cirrhosis presented with symptoms of dyspnoea. Previous extensive investigations had detected no apparent cause. Platypnoea and orthodeoxia were observed.

Twelve tips for the recruitment and retention of general practitioners as teachers of medical students.

Background: Primary care physicians have become a fundamental aspect of teaching in modern medical school curricula worldwide with a significant proportion of undergraduate teaching taking place in primary care. There are calls for this to increase with more patient care occurring in the community but teaching capacity in primary care is a potential challenge. Medical schools, therefore, need strategies to be able to increase their primary care physician teaching workforce.

The prevalence of caries and tooth loss among participants in the Hispanic Community Health Study/Study of Latinos.

Background: The Hispanic and Latino population is projected to increase from 16.7 percent to 30.0 percent by 2050.

Salivary gland involvement in chronic graft-versus-host disease: prevalence, clinical significance, and recommendations for evaluation.

Although xerostomia is a commonly reported complaint in patients with chronic graft-versus-host disease (cGVHD), criteria for evaluating the prevalence and characteristics of salivary gland involvement have not been well defined in this patient population. Previous studies also have made no distinction between salivary and mucosal oral cGVHD. We systematically evaluated signs and symptoms of sicca in a large cohort of patients with cGVHD (n = 101) using instruments widely used to study Sjogren's syndrome.

Aquaporin-1 gene transfer to correct radiation-induced salivary hypofunction.

Irradiation damage to salivary glands is a common iatrogenic consequence of treatment for head and neck cancers. The subsequent lack of saliva production leads to many functional and quality-of-life problems for affected patients and there is no effective conventional therapy. To address this problem, we developed an in vivo gene therapy strategy involving viral vector-mediated transfer of the aquaporin-1 cDNA to irradiation-damaged glands and successfully tested it in two pre-clinical models (irradiated rats and miniature pigs), as well as demonstrated its safety in a large toxicology and biodistribution study.

Management of oral lesions in HIV-positive patients.

HIV/AIDS is currently the leading cause of death in Africa and the fourth leading cause of death worldwide. This systematic review of the literature was conducted to evaluate the evidence for treatment of the most common oral lesions associated with HIV: oral candidiasis with or without oropharyngeal involvement (OPC), oral hairy leukoplakia (OHL), recurrent aphthous-like ulcerations (RAU), oral Kaposi's sarcoma (OKS), orolabial herpes simplex infection (HSV), oral herpes zoster infection (VZV), intraoral or perioral warts (HPV), and HIV-associated periodontal diseases. Treatment of HIV-associated salivary gland disease is addressed in a different section of this World Workshop.

Changes in salivary proteome following allogeneic hematopoietic stem cell transplantation.

Objective: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is frequently complicated by severe infections and graft-vs-host disease (GVHD). Saliva contains many components of adaptive and innate immune response crucial for local host defenses. Changes in salivary constituents could reflect systemic processes such as immune reconstitution and development of GVHD that occur posttransplant.

Chronic graft versus host disease of oral mucosa: review of available therapies.

The use of hematopoetic stem cell transplantation (HSCT) has greatly expanded in the recent years for many neoplastic and hematological disorders. Chronic graft versus host disease (cGVHD) is a major complication of allogeneic HSCT and a major cause of morbidity and mortality. Oral mucosal involvement is frequent in cGVHD and contributes significantly to the overall burden of the condition.

Histopathologic diagnosis of chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. Pathology Working Group Report.

This consensus document provides an update for pathologists and clinicians about the interpretation of biopsy results and use of this information in the management of hematopoietic cell transplantation patients. Optimal sampling and tissue preparation are discussed. Minimal criteria for the diagnosis of graft-versus-host disease (GVHD) are proposed, together with specific requirements for the diagnosis of chronic GVHD.

Transfer of the AQP1 cDNA for the correction of radiation-induced salivary hypofunction.

The treatment of most patients with head and neck cancer includes ionizing radiation (IR). Salivary glands in the IR field suffer significant and irreversible damage, leading to considerable morbidity. Previously, we reported that adenoviral (Ad)-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to rat [C.

Salivary hypofunction and xerostomia: diagnosis and treatment.

Salivary gland hypofunction and complaints of xerostomia are common in elderly patients, irrespective of their living situation. Medication use is frequently related to dry mouth symptoms and reductions in salivary flow rates. Patients with reduced salivary flow are at increased risk for caries, oral fungal infections, swallowing problems, and diminished or altered taste.

Randomized, double-blind, placebo-controlled phase IIb trial of the cyclooxygenase inhibitor ketorolac as an oral rinse in oropharyngeal leukoplakia.

Purpose: Nonselective cyclooxygenase (COX) inhibitors have been reported to decrease the frequency of upper aerodigestive cancers. Ketorolac tromethamine oral rinse has been shown to resolve another COX-dependent process, periodontal disease, without incurring gastrointestinal side effects. This trial evaluated if a topically delivered oral rinse containing ketorolac was as safe as and more effective than oral rinse alone in reducing the area of oral leukoplakia.

A retrospective investigation of advanced periodontal disease as a risk factor for septicemia in hematopoietic stem cell and bone marrow transplant recipients.

Objective: Septicemia is a cause of death in hematopoietic stem cell transplant (HSCT) recipients. Extraction of teeth with advanced periodontitis has been advocated before HSCT to prevent septicemia in myeloablated hosts. The primary aim of the present study was to determine impact of chronic periodontitis, as measured by radiographic alveolar bone loss, on septicemia and transplant mortality.