Clinical trial of a farnesyltransferase inhibitor in children with Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA that produces the farnesylated aberrant lamin A protein, progerin. This multisystem disorder causes failure to thrive and accelerated atherosclerosis leading to early death. Farnesyltransferase inhibitors have ameliorated disease phenotypes in preclinical studies. Twenty-five patients with HGPS received the farnesyltransferase inhibitor lonafarnib for a minimum of 2 y. Primary outcome success was predefined as a 50% increase over pretherapy in estimated annual rate of weight gain, or change from pretherapy weight loss to statistically significant on-study weight gain. Nine patients experienced a ≥50% increase, six experienced a ≥50% decrease, and 10 remained stable with respect to rate of weight gain. Secondary outcomes included decreases in arterial pulse wave velocity and carotid artery echodensity and increases in skeletal rigidity and sensorineural hearing within patient subgroups. All patients improved in one or more of these outcomes. Results from this clinical treatment trial for children with HGPS provide preliminary evidence that lonafarnib may improve vascular stiffness, bone structure, and audiological status.

A Pediatric Hospital Physical Therapy and Occupational Therapy Department's Response to COVID-19: An Administrative Case Report.

OBJECTIVE: The purpose of this case report is to describe the challenges that COVID-19 presented for therapists in a pediatric hospital and the response to these challenges. METHODS: The case report setting is a physical therapy and occupational therapy department (department) of an academic pediatric medical center that provides a range of health care services for children and youth. Challenges that COVID-19 presented to the department included (1) managing safety concerns for patients, their families, and staff; (2) continuing to provide high-quality therapy services within state-mandated restrictions; (3) triaging patients; and (4) keeping clinicians employed and working productively. RESULTS: The department therapists responded to these challenges by (1) increasing communication huddles; (2) developing procedures for staffing and triaging of patients; (3) developing procedures for telehealth therapy services; and (4) designing a remote work program for all department employees. The number of patients and staff on site were reduced by initiating telehealth services, triaging patients, and developing a remote work plan. Communication huddles, department meetings, and supervision meetings were converted to virtual meetings. Staffing rates, patient-care productivity, and department project work were maintained. CONCLUSION: In response to COVID-19, the department developed new protocols and provided information about the protocols, which might be helpful for other pediatric hospitals or outpatient settings when planning for future pandemics or other issues that challenge the ability to provide usual care. Increasing the frequency of verbal and written communication on operational topics is recommended. Primary sources of information from national organizations (eg, the American Physical Therapy Association and the American Occupational Therapy Association) can assist with determining the scope of practice and code of conduct during a pandemic. IMPACT: COVID-19 posed challenges to operations and delivery of patient care. Although this case report is specific to COVID-19, principles applied and lessons learned from this experience can be applied to other emergency situations.

Avoid or engage? Outcomes of graded exposure in youth with chronic pain using a sequential replicated single-case randomized design.

Pain-related fear is typically associated with avoidance behavior and pain-related disability in youth with chronic pain. Youth with elevated pain-related fear have attenuated treatment responses; thus, targeted treatment is highly warranted. Evidence supporting graded in vivo exposure treatment (GET) for adults with chronic pain is considerable, but just emerging for youth. The current investigation represents the first sequential replicated and randomized single-case experimental phase design with multiple measures evaluating GET for youth with chronic pain, entitled GET Living. A cohort of 27 youth (81% female) with mixed chronic pain completed GET Living. For each participant, a no-treatment randomized baseline period was compared with GET Living and 3- and 6-month follow-ups. Daily changes in primary outcomes fear and avoidance and secondary outcomes pain catastrophizing, pain intensity, and pain acceptance were assessed using electronic diaries and subjected to descriptive and model-based inference analyses. Based on individual effect size calculations, a third of participants significantly improved by the end of treatment on fear, avoidance, and pain acceptance. By follow-up, over 80% of participants had improved across all primary and secondary outcomes. Model-based inference analysis results to examine the series of replicated cases were generally consistent. Improvements during GET Living was superior to the no-treatment randomized baseline period for avoidance, pain acceptance, and pain intensity, whereas fear and pain catastrophizing did not improve. All 5 outcomes emerged as significantly improved at 3- and 6-month follow-ups. The results of this replicated single-case experimental phase design support the effectiveness of graded exposure for youth with chronic pain and elevated pain-related fear avoidance.