Use of a novel laparoscopic gastrostomy technique in children with severe epidermolysis bullosa.

OBJECTIVE: Supplementing nutrition in children with severe epidermolysis bullosa (EB) is challenging because of skin and mucosal fragility. Percutaneous endoscopic gastrostomy is contraindicated in EB, whereas more invasive open surgical gastrostomy placement can be complicated by chronic leakage. The aim of the study was to review the efficacy and acceptability, in children with severe EB, of our modified 2-port laparoscopic approach using the Seldinger technique with serial dilatation and tube insertion through a peel-away sheath. METHODS: Retrospective review of children with EB who underwent laparoscopic feeding gastrostomy at our centre since 2009. RESULTS: Seven children (6 severe generalised recessive dystrophic EB, 1 non-Herlitz junctional EB; 2 girls, 5 boys) underwent modified laparoscopic gastrostomy placement at median age 4.85 years (range 1.0-8.8), with fundoplication for gastro-oesophageal reflux in 1 case, with follow-up for 0.3 to 3.9 years. The procedure was well tolerated with oral feeds usually given after 4 hours and whole protein gastrostomy feeds within 24 hours in 6 patients. Improved growth was reflected in mean weight and height z scores: -1.36 (range -2.6 to 0.5) to -0.61 (range -2.34 to 2.0) and -1.09 (range -2.42 to 1.0) to 0.71 (range -1.86 to 1.0), respectively. Postoperatively, 5 patients experienced minor local complications: minimal leakage without skin damage in 3 and transient peristomal granulation rapidly responsive to topical treatment in 2; this followed acute gastrostomy site infection in 1. There was no leakage after the immediate postoperative period. CONCLUSIONS: We conclude that our less-invasive laparoscopic gastrostomy technique is effective and better tolerated in children with severe EB, at least in the medium term, than open gastrostomy placement. Longer follow-up is required.

The effect of pre-event instructions on eyewitness identification.

Research on eyewitness identification often involves exposing participants to a simulated crime and later testing memory using a lineup. We conducted a systematic review showing that pre-event instructions, instructions given before event exposure, are rarely reported and those that are reported vary in the extent to which they warn participants about the nature of the event or tasks. At odds with the experience of actual witnesses, some studies use pre-event instructions explicitly warning participants of the upcoming crime and lineup task. Both the basic and applied literature provide reason to believe that pre-event instructions may affect eyewitness identification performance. In the current experiment, we tested the impact of pre-event instructions on lineup identification decisions and confidence. Participants received non-specific pre-event instructions (i.e., "watch this video") or eyewitness pre-event instructions (i.e., "watch this crime video, you'll complete a lineup later") and completed a culprit-absent or -present lineup. We found no support for the hypothesis that participants who receive eyewitness pre-event instructions have higher discriminability than participants who receive non-specific pre-event instructions. Additionally, confidence-accuracy calibration was not significantly different between conditions. However, participants in the eyewitness condition were more likely to see the event as a crime and to make an identification than participants in the non-specific condition. Implications for conducting and interpreting eyewitness identification research and the basic research on instructions and attention are discussed.

Treatment for chronic pain for adults in the seventh and eighth decades of life: a preliminary study of Acceptance and Commitment Therapy (ACT).

OBJECTIVE: The purpose of this study was to examine results for older adults attending treatment based on Acceptance and Commitment Therapy (ACT) for chronic pain. Both clinical outcome and treatment process variables were examined. SUBJECTS: Participants were 40 adults with chronic pain age 60 and older selected from a larger consecutive sample of 470 adults of any age. The mean age for the smaller study sample was 64.3 years, most were women, 62.5%, and they had longstanding (median 171 months) and highly disabling pain. Intervention. The treatment consisted of 3 or 4 weeks of residential treatment delivered by a team of psychologists, physiotherapists, occupational therapists, nurses, and physicians. It was designed to increase daily functioning not by decreasing pain, but by increasing psychological flexibility. This includes the ability to change or persist with behavior in a practical, accepting, open, aware, values-directed, and committed fashion. RESULTS: Participants showed significant improvements in physical disability, psychosocial disability, and depression at posttreatment and at a 3-month follow-up. They also showed significant increases in components of psychological flexibility. In secondary correlation analyses measures of psychological flexibility were significantly correlated with key outcome measures. CONCLUSION: To our knowledge, this is the first study of ACT for chronic pain specifically looking at older adults, and preliminary results are promising.

US Department of Veterans Affairs Post-Baccalaureate Registered Nurse Residency: Developing Nurses Equipped with Knowledge and Skills to Care for Nation's Veterans.

Nurse residency programs were developed to improve novice nurse competencies, mitigate burnout, lower recruitment costs and nurse attrition, and the quality of patient care. The Office of Academic Affiliations (OAA), US Department of Veterans Affairs (VA), established a 12-month postbaccalaureate nurse residency (PB-RNR) program at 49 sites to develop competent, confident, practice-ready registered nurses equipped with the knowledge and skills to care for veterans. The OAA evaluation of the PB-RNR program demonstrated improved new nurse graduate competence, confidence, recruitment, and retention rates after completion of training at participating VA medical facilities.

Evaluating the use of laparoscopic-assisted gastrostomy tube feeding in children with epidermolysis bullosa: A single-center retrospective study.

BACKGROUND: Nutritional management of children with epidermolysis bullosa (EB) presents multiple challenges including reduced oral intake compounded by mucosal fragility. Gastrostomy tube feeding is effective in improving nutritional status however there is limited data on the safety and tolerance of this technique in EB children. We aim to review the effectiveness and morbidity of our minimally invasive two-port laparoscopic-assisted gastrostomy (LAG) approach using Seldinger techniques with serial dilatations in children with EB. METHODS: A retrospective, observational cohort study was conducted on all consecutive EB patients who underwent LAG tube insertion between 2009 and 2019. Patient demographics, admission details and 12-month clinical outcomes were reported. RESULTS: 32 EB patients underwent LAG placement. Median age at insertion was 7.3 (IQR ± 6.3) years, with 8 (25.0%) and 3 (9.4%) of patients also undergoing oesophageal dilatation and fundoplication, respectively. Minor complications arose in 58.1% of patients including: peri-stomal overgranulation (25.8%), gastrostomy infection (22.6%), pain (22.6%), mild gastrostomy leakage (16.1%), blockage (9.7%) and device failure (3.2%). 2 patients (6.5%) developed major complications with extensive gastrostomy site leakage. Improvements in growth were reflected in mean height Z-scores (-1.99 to -1.71). Mean weight Z-scores improved in patients aged 0-10 years (-2.30 to -1.61) and mean BMI Z-scores increased in patients more than 10 years (-2.71 to -1.46). No cases of gastrostomy-related mortality were reported. CONCLUSION: LAG is well-tolerated in EB patients with improvements in growth and minimal morbidity 12-months post-gastrostomy insertion. An extended follow-up period is required to ascertain the long-term implications of gastrostomy feeding.

Erratum: Erratum.

[This corrects the article DOI: 10.1177/11795484221119316.].

Efficacy and Safety of LY3127804, an Anti-Angiopoietin-2 Antibody, in a Randomized, Double-Blind, Placebo-Controlled Clinical Trial in Patients Hospitalized with Pneumonia and Presumed or Confirmed COVID-19.

BACKGROUND: Severe cases of coronavirus disease 2019 (COVID-19) are characterized by progressive respiratory failure and the development of acute respiratory distress syndrome (ARDS), with high mortality rates for patients requiring mechanical ventilation. Levels of the vascular growth factor Angiopoietin 2 (Ang2) in plasma have been strongly correlated with increased ARDS risk in patients with pneumonia or sepsis. The intent of this study was to determine whether LY3127804, an anti-Ang2 monoclonal antibody, could reduce the need for mechanical ventilation among patients admitted to the hospital with pneumonia and presumed or confirmed COVID-19. METHODS: Patients admitted to hospital with confirmed pneumonia, presumed or confirmed COVID-19, and infiltrates on chest imaging and/or oxygen saturation of ≤ 95% on room air were stratified by age group (< 65 years and ≥ 65 years), sex, and site and randomly assigned 1:1 within each stratum to receive either LY3127804 (20 mg/kg) or placebo on Day 1 and possibly on Day 15. The primary end point for this study was number of days in which a patient did not require a ventilator over the 28-day study period. RESULTS: Interim analysis assessed study futility after 95 randomized patients had 28-day data available and showed no benefit of LY3127804 in reducing the number of ventilator days over placebo. The study was subsequently terminated. CONCLUSION: LY3127804 treatment did not decrease the need for ventilator usage in patients hospitalized with pneumonia and presumed or confirmed COVID-19. ClinicalTrialsgov identifier: NCT04342897.

Resting Energy Expenditure and Protein Balance in People with Epidermolysis Bullosa.

Epidermolysis bullosa (EB) is a group of conditions characterized by severe fragility of the skin that causes recurring blistering. The recessive dystrophic subtype of EB (RDEB) has a strong impact on the nutritional status. We evaluated the resting energy expenditure (REE) and presence of protein catabolism in patients with RDEB. REE was assessed in 10 subjects (7 females; age range 4-33 years) by indirect calorimetry and using a predictive equation. Nitrogen balance was calculated by protein intake and 24 h urinary urea excretion estimations. An assessment of body surface area (BSA) with infected and non-infected skin lesions was applied to the nitrogen balance burn equation that was adapted to EB. The REE values predicted by the equation were consistently lower than the ones measured, except for two subjects. All subjects recorded high protein and energy intake, with protein intake being higher than 4 g protein/kg/day for five subjects. Even so, protein catabolism was observed in six subjects, three of whom had infected wounds. This study raises the hypothesis that the clinical and nutritional risks of people with RDEB are associated with an increased REE and negative nitrogen balance, which reinforces the importance of nutritional support.

A decade of innovation in pharmaceutical R&D: the Chorus model.

Chorus is a small, operationally independent clinical development organization within Eli Lilly and Company that specializes in drug development from candidate selection to clinical proof of concept. The mission of Chorus is to achieve proof of concept rapidly and at a low cost while positioning successful projects for 'pharma-quality' late-stage development. Chorus uses a small internal staff of experienced drug developers and a network of external vendors to design and implement chemistry, manufacturing and control processes, preclinical toxicology and biology, and Phase I/II clinical trials. In the decade since it was established, Chorus has demonstrated substantial productivity improvements in both time and cost compared to traditional pharmaceutical research and development. Here, we describe its development philosophy, organizational structure, operational model and results to date.

Inverse dynamics modelling of upper-limb tremor, with cross-correlation analysis.

A method to characterise upper-limb tremor using inverse dynamics modelling in combination with cross-correlation analyses is presented. A 15 degree-of-freedom inverse dynamics model is used to estimate the joint torques required to produce the measured limb motion, given a set of estimated inertial properties for the body segments. The magnitudes of the estimated torques are useful when assessing patients or evaluating possible intervention methods. The cross-correlation of the estimated joint torques is proposed to gain insight into how tremor in one limb segment interacts with tremor in another. The method is demonstrated using data from a single patient presenting intention tremor because of multiple sclerosis. It is shown that the inertial properties of the body segments can be estimated with sufficient accuracy using only the patient's height and weight as a priori knowledge, which ensures the method's practicality and transferability to clinical use. By providing a more detailed, objective characterisation of patient-specific tremor properties, the method is expected to improve the selection, design and assessment of treatment options on an individual basis.

Estimation of upper-limb orientation based on accelerometer and gyroscope measurements.

A solution is proposed to the estimation of upper-limb orientation using miniature accelerometers and gyroscopes. This type of measurement device has many different possible applications, ranging from clinical use with patients presenting a number of conditions such as upper motor neuron syndrome and pathologies that give rise to loss of dexterity, to competitive sports training and virtual reality. Here we focus on a design that minimizes the number of sensors whilst delivering estimates of known accuracy over a defined frequency range. Minimizing the sensor count can make the measurement system less obtrusive, as well as minimising cost and reducing the required bandwidth if using a wireless solution. Accurate measurement of movement amplitude up to 15 Hz is required in our immediate application, namely to quantify tremor in multiple sclerosis patients. The drive for low numbers of sensors and good accuracy at higher frequencies leads to a novel design based on composite filters. The simple estimator structure also gives good insight into the fundamental accuracy limitations based on the sensors chosen. This paper defines the underlying mathematics, and quantifies performance for an estimator for shoulder, upper arm, lower arm and hand orientations. Good estimation accuracy up to 15 Hz is indicated, and this with a reduced total sensor count of 18 compared to 24 that would be required for more conventional estimator architectures.