Clinical Trial Considerations in Developing Treatments for Early Stages of Common, Chronic Kidney Diseases: A Scientific Workshop Cosponsored by the National Kidney Foundation and the US Food and Drug Administration.

In the past decade, advances in the validation of surrogate end points for chronic kidney disease (CKD) progression have heightened interest in evaluating therapies in early CKD. In December 2020, the National Kidney Foundation sponsored a scientific workshop in collaboration with the US Food and Drug Administration (FDA) to explore patient, provider, and payor perceptions of the value of treating early CKD. The workshop reviewed challenges for trials in early CKD, including trial designs, identification of high-risk populations, and cost-benefit and safety considerations. Over 90 people representing a range of stakeholders including experts in clinical trials, nephrology, cardiology and endocrinology, patient advocacy organizations, patients, payors, health economists, regulators and policy makers attended a virtual meeting. There was consensus among the attendees that there is value to preventing the development and treating the progression of early CKD in people who are at high risk for progression, and that surrogate end points should be used to establish efficacy. Attendees also concluded that cost analyses should be holistic and include aspects beyond direct savings for treatment of kidney failure; and that safety data should be collected outside/beyond the duration of a clinical trial. Successful drug development and implementation of effective therapies will require collaboration across sponsors, patients, patient advocacy organizations, medical community, regulators, and payors.

The Theory and Art of Child Psychotherapy: A Corrective Developmental Approach.

The history of child psychotherapy is sketched from the psychoanalytic pioneers Anna Freud and Melanie Klein to the popular "nondirective" approach of Virginia Axline. The author's approach to child psychotherapy, based on contemporary psychoanalytic theories, allows the therapist to play any parental role that helps to repair developmental deficiencies and conflicts. These include nurturing, supporting, mirroring, role modeling, challenging, and limit setting. Following Winnicott, psychotherapy is conceived as a play space in which therapist and child are both spontaneous. The value of interpretation and insight in child therapy is discussed. There follows a more detailed discussion of three major problem areas in child psychotherapy: handling anger and hostile aggression; handling issues related to sexuality; and handling narcissistic issues of inferiority and shame.

Spatiotemporal trajectories of reactivation of somatosensory cortex by direct and secondary pathways after dorsal column lesions in squirrel monkeys.

After lesions of the somatosensory dorsal column (DC) pathway, the cortical hand representation can become unresponsive to tactile stimuli, but considerable responsiveness returns over weeks of post-lesion recovery. The reactivation suggests that preserved subthreshold sensory inputs become potentiated and axon sprouting occurs over time to mediate recovery. Here, we studied the recovery process in 3 squirrel monkeys, using high-resolution cerebral blood volume-based functional magnetic resonance imaging (CBV-fMRI) mapping of contralateral somatosensory cortex responsiveness to stimulation of distal finger pads with low and high level electrocutaneous stimulation (ES) before and 2, 4, and 6weeks after a mid-cervical level contralateral DC lesion. Both low and high intensity ES of digits revealed the expected somatotopy of the area 3b hand representation in pre-lesion monkeys, while in areas 1 and 3a, high intensity stimulation was more effective in activating somatotopic patterns. Six weeks post-lesion, and irrespective of the severity of loss of direct DC inputs (98%, 79%, 40%), somatosensory cortical area 3b of all three animals showed near complete recovery in terms of somatotopy and responsiveness to low and high intensity ES. However there was significant variability in the patterns and amplitudes of reactivation of individual digit territories within and between animals, reflecting differences in the degree of permanent and/or transient silencing of primary DC and secondary inputs 2weeks post-lesion, and their spatio-temporal trajectories of recovery between 2 and 6weeks. Similar variations in the silencing and recovery of somatotopy and responsiveness to high intensity ES in areas 3a and 1 are consistent with individual differences in damage to and recovery of DC and spinocuneate pathways, and possibly the potentiation of spinothalamic pathways. Thus, cortical deactivation and subsequent reactivation depends not only on the degree of DC lesion, but also on the severity and duration of loss of secondary as well as primary inputs revealed by low and high intensity ES.

Transforming mental health care for children and their families.

In April 2002, the President's New Freedom Commission on Mental Health was created by executive order to study the mental health care delivery system in our nation and to make recommendations for improvements so that individuals with serious mental disorders can live, work, learn, and fully participate in their homes and communities. In its report, "Achieving the Promise: Transforming Mental Health Care in America," the commission provided strategies to address critical infrastructure, practice, and research issues. This article focuses on the work of the commission's Subcommittee on Children and Families, describing its vision for mental health service delivery for children and providing suggestions for strengthening community-based care for youths with or at risk of behavioral health disorders. Training, research, practice, and policy implications for psychologists are discussed.