Fundamental principles of rehabilitation and musculoskeletal tissue healing

OBJECTIVE: To review fundamental principles of tissue healing and physical rehabilitation as they apply to dogs recovering from cranial cruciate ligament (CCL) surgery STUDY DESIGN: Invited Review SAMPLE POPULATION: None METHODS: A multidisciplinary group of specialists in small animal surgery, rehabilitation/sports medicine, and human physical and occupational therapy reviewed the currently available evidence for rehabilitation post-CCL surgery. Because current evidence is limited, this group proposes guidelines for rehabilitation after CCL surgery based on the fundamental principles of tissue healing and physical therapy RESULTS: This Review proposes four fundamental principles of small animal physical rehabilitation based on the foundations of tissue healing and patient-centric and goal-oriented therapy. Postoperative rehabilitation programs should be designed such that patient progress is based on individual assessment according to the degree of tissue healing, strength, and achievement of functional goals. Therapists must fully understand phases of tissue healing, reassess the patient frequently, and use clinical reasoning skills to progress treatment appropriately for the individual patient. CONCLUSION: Until more robust evidence is available to guide treatment protocols, fundamental principles of rehabilitation should ideally be adhered to when providing rehabilitation, including after CCL surgery. CLINICAL SIGNIFICANCE: While this Review specifically addresses post-CCL surgery rehabilitation, these fundamental principles should be applied broadly to animals enrolled in rehabilitation programs

Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants

© 2015 Australasian Society for Immunology Inc. Respiratory syncytial virus (RSV) infection remains a significant global health burden disproportionately affecting infants and leading to long-term lung disease. Interleukin (IL)-17A has been shown to be involved in regulating viral and allergic lung inflammatory responses, which has led to a more recent interest in its role in RSV infection. Using a neonatal mouse model of RSV, we demonstrate that neonates fail to develop IL-17A responses compared with adult mice; the main immediate IL-17A contributor in adults were γδ T cells. Antibody neutralization of IL-17A in adult mice caused increased lung inflammation and airway mucus from RSV, whereas exogenous IL-17A administration to RSV-infected neonates caused decreased inflammation but no change in airway mucus. We also observed a lack of pro-inflammatory cytokine production (IL-1β, IL-6) from infected neonates. Using human cord blood mononuclear cells (CBMCs) and adult peripheral blood mononuclear cells (PBMCs), we compared inflammasome activation by direct retinoic acid-inducible gene I agonism; CBMCs failed to induce pro-inflammatory cytokines or IL-17A+γδ T cells compared with PBMCs. Our results indicate that RSV disease severity is in part mediated by a lack of inflammasome activation and IL-17A production in neonates

Observation of bosonic coalescence of photon pairs

Quantum theory predicts that two indistinguishable photons incident on a beam-splitter interferometer stick together as they exit the device (the pair emerges randomly from one port or the other). We use a special photon-number-resolving energy detector for a direct loophole-free observation of this quantum-interference phenomenon. Simultaneous measurements from two such detectors, one at each beam-splitter output port, confirm the absence of cross-coincidences.Comment: 4 pages, 2 figures, submitted to Phys. Rev. Let

Impact of sensor and measurement timing errors on model-based insulin sensitivity

peer reviewe

Impact of sensor and measurement timing errors on model-based insulin sensitivity

peer reviewe

Implementation and evaluation of the SPRINT protocol for tight glycaemic control in critically ill patients: a clinical practice change

SPRINT was implemented as a clinical practice change in a general intensive care unit (ICU). The objective of this study was to measure the effect of the SPRINT protocol on glycaemic control and mortality compared to previous ICU control methods. Glycaemic control and mortality outcomes for 371 SPRINT patients with median acute physiology and chronic health evaluation (APACHE II) score 18 [IQR: 15-24] are compared to a 413 patient retrospective cohort with median APACHE II score of 18 [IQR: 15-23]

Validation of a model-based virtual trials method for tight glycemic control in intensive care

peer reviewedBACKGROUND: In-silico virtual patients and trials offer significant advantages in cost, time and safety for designing effective tight glycemic control (TGC) protocols. However, no such method has fully validated the independence of virtual patients (or resulting clinical trial predictions) from the data used to create them. This study uses matched cohorts from a TGC clinical trial to validate virtual patients and in-silico virtual trial models and methods. METHODS: Data from a 211 patient subset of the Glucontrol trial in Liege, Belgium. Glucontrol-A (N = 142) targeted 4.4-6.1 mmol/L and Glucontrol-B (N = 69) targeted 7.8-10.0 mmol/L. Cohorts were matched by APACHE II score, initial BG, age, weight, BMI and sex (p > 0.25). Virtual patients are created by fitting a clinically validated model to clinical data, yielding time varying insulin sensitivity profiles (SI(t)) that drives in-silico patients.Model fit and intra-patient (forward) prediction errors are used to validate individual in-silico virtual patients. Self-validation (tests A protocol on Group-A virtual patients; and B protocol on B virtual patients) and cross-validation (tests A protocol on Group-B virtual patients; and B protocol on A virtual patients) are used in comparison to clinical data to assess ability to predict clinical trial results. RESULTS: Model fit errors were small (<0.25%) for all patients, indicating model fitness. Median forward prediction errors were: 4.3, 2.8 and 3.5% for Group-A, Group-B and Overall (A+B), indicating individual virtual patients were accurate representations of real patients. SI and its variability were similar between cohorts indicating they were metabolically similar.Self and cross validation results were within 1-10% of the clinical data for both Group-A and Group-B. Self-validation indicated clinically insignificant errors due to model and/or clinical compliance. Cross-validation clearly showed that virtual patients enabled by identified patient-specific SI(t) profiles can accurately predict the performance of independent and different TGC protocols. CONCLUSIONS: This study fully validates these virtual patients and in silico virtual trial methods, and clearly shows they can accurately simulate, in advance, the clinical results of a TGC protocol, enabling rapid in silico protocol design and optimization. These outcomes provide the first rigorous validation of a virtual in-silico patient and virtual trials methodology

Organ failure and tight glycemic control in the SPRINT study

INTRODUCTION: Intensive care unit mortality is strongly associated with organ failure rate and severity. The sequential organ failure assessment (SOFA) score is used to evaluate the impact of a successful tight glycemic control (TGC) intervention (SPRINT) on organ failure, morbidity, and thus mortality. METHODS: A retrospective analysis of 371 patients (3,356 days) on SPRINT (August 2005 - April 2007) and 413 retrospective patients (3,211 days) from two years prior, matched by Acute Physiology and Chronic Health Evaluation (APACHE) III. SOFA is calculated daily for each patient. The effect of the SPRINT TGC intervention is assessed by comparing the percentage of patients with SOFA 2) are also compared. Cumulative time in 4.0 to 7.0 mmol/L band (cTIB) was evaluated daily to link tightness and consistency of TGC (cTIB >/=0.5) to SOFA /=0.5 (37% Pre-SPRINT) reaching 100% by Day 7 (50% Pre-SPRINT). Conditional and joint probabilities indicate tighter, more consistent TGC under SPRINT (cTIB >/=0.5) increased the likelihood SOFA /=0.5 metric provides a first benchmark linking TGC quality to organ failure. These results support other physiological and clinical results indicating the role tight, consistent TGC can play in reducing organ failure, morbidity and mortality, and should be validated on data from randomised trials

Pilot proof of concept clinical trials of Stochastic Targeted (STAR) glycemic control

ABSTRACT: INTRODUCTION: Tight glycemic control (TGC) has shown benefits but has been difficult to achieve consistently. STAR (Stochastic TARgeted) is a flexible, model-based TGC approach directly accounting for intra- and inter- patient variability with a stochastically derived maximum 5% risk of blood glucose (BG) /=3 days. Written informed consent was obtained for all patients, and approval was granted by the NZ Upper South A Regional Ethics Committee. RESULTS: A total of 402 measurements were taken over 660 hours (~14/day), because nurses showed a preference for 2-hourly measurements. Median [interquartile range, (IQR)] cohort BG was 5.9 mmol/L [5.2-6.8]. Overall, 63.2%, 75.9%, and 89.8% of measurements were in the 4.0-6.5, 4.0-7.0, and 4.0-8.0 mmol/L bands. There were no hypoglycemic events (BG < 2.2 mmol/L), and the minimum BG was 3.5 mmol/L with 4.5% < 4.4 mmol/L. Per patient, the median [IQR] hours of TGC was 92 h [29-113] using 53 [19-62] measurements (median, ~13/day). Median [IQR] results: BG, 5.9 mmol/L [5.8-6.3]; carbohydrate nutrition, 6.8 g/h [5.5-8.7] (~70% goal feed median); insulin, 2.5 U/h [0.1-5.1]. All patients achieved BG < 6.1 mmol/L. These results match or exceed SPRINT and clinical workload is reduced more than 20%. CONCLUSIONS: STAR TGC modulating insulin and nutrition inputs provided very tight control with minimal variability by managing intra- and inter- patient variability. Performance and safety exceed that of SPRINT, which reduced mortality and cost in the Christchurch ICU. The use of glucometers did not appear to impact the quality of TGC. Finally, clinical workload was self-managed and reduced 20% compared with SPRINT