The lack of standardized criteria for quantitative measurement of therapeutic response in clinical trials poses a major obstacle for the development of new agents in chronic graft-versus-host disease (GVHD). This consensus document was developed to address several objectives for response criteria to be used in chronic GVHD-related clinical trials. The proposed measures should be practical for use both by transplantation and nontransplantation medical providers, adaptable for use in adults and in children, and focused on the most important chronic GVHD manifestations. The measures should also give preference to quantitative, rather than semiquantitative, measures; capture information regarding signs, symptoms, and function separately from each other; and use validated scales whenever possible to demonstrate improved patient outcomes and meet requirements for regulatory approval of novel agents. Based on these criteria, we propose a set of measures to be considered for use in clinical trials, and forms for data collection are provided (). Measures should be made at 3-month intervals and whenever major changes are made in treatment. Provisional definitions of complete response, partial response, and progression are proposed for each organ and for overall outcomes. The proposed response criteria are based on current expert consensus opinion and are intended to improve consistency in the conduct and reporting of chronic GVHD trials, but their use remains to be demonstrated in practice.

In 2005, the NIH Chronic GVHD Consensus Response Criteria Working Group recommended several measures to document serial evaluations of chronic GVHD organ involvement. Provisional definitions of complete response, partial response, and progression were proposed for each organ and for overall outcome. Based on publications over the last nine years, the 2014 Working Group has updated its recommendations for measures and interpretation of organ and overall responses. Major changes include elimination of several clinical parameters from the determination of response, updates to or addition of new organ scales to assess response, and the recognition that progression excludes minimal, clinically insignificant worsening that does not usually warrant a change in therapy. The response definitions have been revised to reflect these changes and are expected to enhance reliability and practical utility of these measures in clinical trials. Clarification is provided about response assessment after the addition of topical or organ-targeted treatment. Ancillary measures are strongly encouraged in clinical trials. Areas suggested for additional research include criteria to identify irreversible organ damage and validation of the modified response criteria, including in the pediatric population.

Moderate to severe chronic graft-versus-host disease (GVHD) is treated with potent immunosuppressive therapy (IST) to modulate the allo-immune response, control symptoms, and prevent further organ damage. We sought to understand the types of treatments used in clinical practice and the likelihood of successful treatment associated with each. A chart review was performed for 250 adult patients at Fred Hutchinson Cancer Research Center enrolled in a prospective observational study. After a median follow-up of 5.6 years for survivors, approximately one-third were still on IST (of whom half were on fourth or greater line of therapy), one-third were alive and off IST, and one-third had relapsed or died. Approximately half of survivors stopped all IST at least once, although half of these restarted IST after a median of 3.4 months (interquartile range, 2.3 to 8.0) off therapy. Successful discontinuation of IST for at least 9 months was associated with myeloablative conditioning (P = .04), more years since transplant (P = .009), and lack of oral (P < .001) and skin (P = .049) involvement compared with those who had to restart IST. We conclude that patients with chronic GVHD usually receive multiple lines and years of IST, with only a third off IST, alive, and free of malignancy at 5 years after chronic GVHD diagnosis. Patients stopping IST should be cautioned to self-monitor and continue close medical follow-up, especially for 3 to 6 months after stopping IST.

Adequate nutrition during the pre- and early-postnatal periods plays a critical role in programming early neurodevelopment. Disruption of neurodevelopment by nutritional deficiencies can result not only in lasting functional deficits, but increased risk of neuropsychiatric disease in adulthood. Historical periods of famine such as the Dutch Hunger Winter and the Chinese Famine have provided foundational evidence for the long-term effects of developmental malnutrition on neuropsychiatric outcomes. Because neurodevelopment is a complex process that consists of many nutrient- and brain-region specific critical periods, subsequent clinical and pre-clinical studies have aimed to elucidate the specific roles of individual macro- and micronutrient deficiencies in neurodevelopment and neuropsychiatric pathologies. This review will discuss developmental iron deficiency (ID), the most common micronutrient deficiency worldwide, as a paradigm for understanding the role of early-life nutrition in neurodevelopment and risk of neuropsychiatric disease. We will review the epidemiologic data linking ID to neuropsychiatric dysfunction, as well as the underlying structural, cellular, and molecular mechanisms that are thought to underlie these lasting effects. Understanding the mechanisms driving lasting dysfunction and disease risk is critical for development and implementation of nutritional policies aimed at preventing nutritional deficiencies and their long-term sequelae.

METHODS:The Colorado Hospitals Substance Exposed Newborn Quality Improvement Collaborative is a consortium of neonatal providers, public health experts, and legislative experts that provides infrastructure and resources for Colorado birthing hospitals to undertake initiatives focused on improving the care of OENs. The Colorado Hospitals Substance Exposed Newborn Quality Improvement Collaborative was started in September 2017 and includes 19 birthing hospitals in Colorado, with 12 contributing data to the centralized database. The interventions were focused on (1) hospital engagement and (2) increasing nonpharmacologic care (by using the Eat, Sleep, Console assessment tool; developing guidelines for breastfeeding eligibility; employing comfort measures before pharmacologic therapy; and administering opiate therapy on an as-needed basis). RESULTS:From April 2017 to December 2019, 787 OENs were identified. Among infants $35 weeks' gestational age without other medical diagnoses (n 5 647), statistical process control charts revealed significant reduction in the primary outcome of interest, average hospital LOS, from 14.8 to 5.9 days. For all OENs, receipt of pharmacologic therapy declined from 61% to 23%. Among OENs who received pharmacologic therapy (and were $35 weeks' gestational age without other medical diagnoses), average LOS also declined from 21.9 to 8.0 days. CONCLUSIONS:Through standardization of OEN care focused on family engagement and nonpharmacologic care, this statewide collaborative reduced average LOS, the percentage of OENs requiring opiate therapy, and average LOS for OENs requiring opiate therapy.