Pilot evaluation of a novel unilateral onychectomy model and efficacy of an extended release buprenorphine product

Abstract Background Non-steroidal anti-inflammatory drugs (NSAIDs), transdermal fentanyl patches, and transmucosal buprenorphine are probably the most commonly used options for providing post-operative analgesia in the early at-home period. However, these require daily administration or are associated with abuse concerns. One of the significant unmet needs in veterinary surgery and pain management is for longer acting opioids for cats to effectively bridge the gap between the in-hospital and at-home recovery periods. A proof of concept study of an extended release formulation of buprenorphine HCL (ER-Bup) was conducted using objective kinetic measures and a unilateral onychectomy model. Using a blinded, randomized, two period crossover design, four cats were allocated to control (saline) or ER-Bup (0.6 mg/kg, subcutaneously [SC]) treatment groups. All animals underwent a unilateral forelimb onychectomy per period with a washout/recovery period in between. Observational pain scores and kinetic data (using a pressure sensitive walkway [PSW]) were collected prior to (baseline) and at intervals for 72 h following surgery. Symmetry indices were derived for kinetic variables (peak vertical force [PVF]; vertical impulse [VI]) of each forelimb for landing following a jump and for walking. A rescue analgesic protocol was in place. Effect of surgery and treatment were evaluated using a mixed model statistical approach. Results No cats required rescue analgesics based on subjective pain score. ER-Bup had a positive influence on subjective pain scores during the 72 h postsurgery (p = 0.0473). PVF and VI of the operated limb were significantly decreased for both landing (p < 0.0001 and p < 0.0001) and walking (p < 0.0001 and p < 0.0001 respectively) compared to control. ER-Bup resulted in significantly decreased asymmetry in limb use during landing (PVF, p < 0.0001; VI, p < 0.0001) and walking (PVF, p = 0.0002, VI, p < 0.0001). The novel use of data collected following a jump from an elevated platform appeared to provide all desired information and was easier to collect than walking data. Conclusion This study demonstrates that SC administration of ER-Bup may be an effective analgesic for a 72 h period postoperatively. Furthermore, landing onto a PSW from an elevated perch may be a useful and efficient way to assess analgesics in cats using a unilateral model of limb pain

Modelos de predicción de mortalidad en cirugía cardiaca: diseño de un modelo, evaluación de modelos generales y análisis de mortalidad ajustada a riesgo

Las intervenciones de cirugía cardiaca tienen costes elevados, emplean recursos complejos, y se asocian a riesgos quirúrgicos medios comparativamente más elevados que la mayor parte de las demás disciplinas quirúrgicas. Es un área de especial interés para los estudios de evaluación de riesgo y de análisis de calidad. El parámetro más empleado como variable de medición es la mortalidad hospitalaria, por su relevancia clínica, facilidad de medir, y estandarización. La necesidad de establecer rangos de mortalidad aceptable ha originado iniciativas nacionales para medirlo. Ningún organismo emite datos de mortalidad por tipo de procedimiento ajustado a riesgo de los servicios cardioquirúrgicos adaptados a criterios acordados con las sociedades científicas. Las fuentes existentes son las memorias de resultados de las Consejerías, los registros de gastos y el Registro de Actividad de la SECTCV. Ninguna de estas fuentes contiene información paciente a paciente, ni información pronóstica de los pacientes. La fuente más útil a nivel clínico es el Registro de Intervenciones de la SECTCV. El análisis de la mortalidad debe tener en cuenta el riesgo de los pacientes. Los modelos de predicción de mortalidad estiman este riesgo..

Vitamin D to prevent lung injury following esophagectomy: A randomized, placebo-controlled trial

Objectives: Observational studies suggest an association between vitamin D deficiency and adverse outcomes of critical illness and identify it as a potential risk factor for the development of lung injury. To determine whether pre-operative administration of oral high-dose cholecalciferol ameliorates early acute lung injury post-operatively in adults undergoing elective esophagectomy. Design: A double-blind, randomized, placebo-controlled trial. Setting: Three large UK university hospitals. Patients: Seventy-nine adult patients undergoing elective esophagectomy were randomized. Intervention: A single oral preoperative (3-14 days) dose of 7.5mg (300,000IU; 15mls) cholecalciferol or matched placebo. Measurements and Main Results: Primary outcome was change in extravascular lung water index (EVLWI) at the end of esophagectomy. Secondary outcomes included PaO2:FiO2 ratio, development of lung injury, ventilator and organ-failure free days, 28 and 90 day survival, safety of cholecalciferol supplementation, plasma vitamin D status (25(OH)D, 1,25(OH)2D and vitamin D binding protein), pulmonary vascular permeability index (PVPI) and EVLWI day 1 postoperatively. An exploratory study measured biomarkers of alveolar-capillary inflammation and injury. Forty patients were randomized to cholecalciferol and 39 to placebo. There was no significant change in EVLWI at the end of the operation between treatment groups (placebo median 1.0[IQR 0.4 – 1.8] vs cholecalciferol median 0.4[IQR 0.4 – 1.2] ml/kg, p=0.059). Median PVPI values were significantly lower in the cholecalciferol treatment group (placebo 0.4[IQR 0 – 0.7] vs cholecalciferol 0.1[IQR -0.15 -0.35], p=0.027). Cholecalciferol treatment effectively increased 25(OH)D concentrations but surgery resulted in a decrease in 25(OH)D concentrations at day 3 in both arms. There was no difference in clinical outcomes. Conclusions: High-dose preoperative treatment with oral cholecalciferol was effective at increasing 25(OH)D concentrations, and reduced changes in postoperative PVPI but not EVLWI

Extension of a Multiscale Particle Scheme to Near-Equilibrium Viscous Flows

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76880/1/AIAA-40262-641.pd

Prospective external validation of the Predicting Out-of-OFfice Blood Pressure (PROOF-BP) strategy for triaging ambulatory monitoring in the diagnosis and management of hypertension: observational cohort study

Objectives: Triaging patients with suspected high blood pressure for ambulatory blood pressure monitoring (ABPM), on the basis of their clinic blood pressure and characteristics, may reduce the need for ABPM. This study aimed to prospectively validate this new approach using data from routine practice.Design: Prospective observational cohort study.Setting: Ten primary care practices and one hospital in the UK. Participants: Consecutive patients aged >18 years referred for ABPM in routine practice.Interventions: All patients underwent ABPM and had the new triage algorithm (PROOF-BP) applied. Main outcome measures: Proportion correctly classified with hypertension using the triaging strategy compared to the reference standard of daytime ABPM. Sensitivity, specificity and area under the receiver operator characteristic curve (AUROC) for detecting hypertension.Results: A total of 887 patients (mean age 52.8±16.2 years) were referred for ABPM and enrolled during the study period. The triaging strategy correctly classified hypertensive status in 801 patients (90%, 95% CI 88% to 92%) and had a sensitivity of 97% (95% CI 96% to 99%) and specificity of 76% (95% CI 71% to 81%) for hypertension. The AUROC was 0.86 (95% CI 0.84 to 0.89). Use of triaging, rather than uniform referral for ABPM in routine practice would have resulted in 435 patients (49%, 95% CI 46% to 52%) being referred for ABPM and the remainder managed on the basis of their clinic measurements. Of these, 69 (8%, 95% CI 6% to 10%) would have received treatment that would have been deemed unnecessary had they received ABPM. Conclusions: In a population of patients referred for ABPM, this new triaging approach accurately classified hypertensive status for most, with half the utilisation of ABPM compared with usual care. This triaging strategy can therefore be recommended for diagnosis or management of hypertension in patients where ABPM is being considered, particularly in settings where resources may be limited

Predicting Out-of-Office Blood Pressure in the Clinic for the Diagnosis of Hypertension in Primary Care: An Economic Evaluation

Clinical guidelines in the United States and United Kingdom recommend that individuals with suspected hypertension should have ambulatory blood pressure (BP) monitoring to confirm the diagnosis. This approach reduces misdiagnosis because of white coat hypertension but will not identify people with masked hypertension who may benefit from treatment. The Predicting Out-of-Office Blood Pressure (PROOF-BP) algorithm predicts masked and white coat hypertension based on patient characteristics and clinic BP, improving the accuracy of diagnosis while limiting subsequent ambulatory BP monitoring. This study assessed the cost-effectiveness of using this tool in diagnosing hypertension in primary care. A Markov cost–utility cohort model was developed to compare diagnostic strategies: the PROOF-BP approach, including those with clinic BP ≥130/80 mm Hg who receive ambulatory BP monitoring as guided by the algorithm, compared with current standard diagnostic strategies including those with clinic BP ≥140/90 mm Hg combined with further monitoring (ambulatory BP monitoring as reference, clinic, and home monitoring also assessed). The model adopted a lifetime horizon with a 3-month time cycle, taking a UK Health Service/Personal Social Services perspective. The PROOF-BP algorithm was cost-effective in screening all patients with clinic BP ≥130/80 mm Hg compared with current strategies that only screen those with clinic BP ≥140/90 mm Hg, provided healthcare providers were willing to pay up to £20 000 ($26 000)/quality-adjusted life year gained. Deterministic and probabilistic sensitivity analyses supported the base-case findings. The PROOF-BP algorithm seems to be cost-effective compared with the conventional BP diagnostic options in primary care. Its use in clinical practice is likely to lead to reduced cardiovascular disease, death, and disability

Evaluation of a new model of care for people with complications of diabetic retinopathy : The EMERALD Study

Objectives The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent and life-long follow-up, have markedly increased hospital demands. Resulting delays in the evaluation/treatment of patients are leading to sight loss. Strategies to increase capacity of medical retina clinics are urgently needed. EMERALD tested diagnostic accuracy, acceptability and costs of a new health care pathway for people with previously treated DME/PDR. Design Prospective, multicentric, case-referent, cross-sectional, diagnostic accuracy study, undertaken in 13 hospitals in the United Kingdom. Participants Adults with type 1 or 2 diabetes and previously successfully treated DME/PDR who, at the time of enrolment, had active or inactive disease. Methods A new health care pathway entailing multimodal imaging (spectral domain optical coherence tomography [SD-OCT] for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-wide-field fundus images [UWF] for PDR) interpreted by trained non-medical staff (ophthalmic graders) to detect re-activation of disease was compared with the current standard care (ophthalmologists face-to-face examination). Main outcome measures Primary outcome: sensitivity of the new pathway. Secondary outcomes: specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, with inadequate images/indeterminate findings. Results The new pathway had sensitivity of 97% (95% confidence interval [CI] 92-99%) and specificity of 31% (95% CI 23-40%) to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS (85%, 95% CI 77-91%; 48%; 95% CI 41-56%, respectively) or UWF (83%, 95% CI 75-89%; 54%; 95% CI 46-61%, respectively) were comparable. For detection of high risk PDR sensitivity and specificity were higher when using UWF images (87%, 95% CI 78-93%; 49% 95% CI 42-56%, respectively for UWF, versus 80%, 95% CI 69-88%; 40% CI 34-47%, respectively, for 7-field ETDRS). Participants preferred ophthalmologist’s assessments; in their absence, wished immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard care, the new pathway could save £1,390/100 DME visits and between £461-£1,189/100 PDR visits. Conclusion The new ophthalmic grader pathway has acceptable sensitivity and would release resources. Users’ suggestions should guide implementatio

Systematic KMTNet planetary anomaly search. VIII. Complete sample of 2019 subprime field planets

We complete the publication of all microlensing planets (and “possible planets”) identified by the uniform approach of the KMT AnomalyFinder system in the 21 KMT subprime fields during the 2019 observing season, namely, KMT-2019-BLG-0298, KMT-2019-BLG-1216, KMT-2019-BLG-2783, OGLE-2019-BLG-0249, and OGLE-2019-BLG-0679 (planets), as well as OGLE-2019-BLG-0344 and KMT-2019-BLG-0304 (possible planets). The five planets have mean log mass ratio measurements of (−2.6, −3.6, −2.5, −2.2, −2.3), median mass estimates of (1.81, 0.094, 1.16, 7.12, 3.34) M Jup, and median distance estimates of (6.7, 2.7, 5.9, 6.4, 5.6) kpc, respectively. The main scientific interest of these planets is that they complete the AnomalyFinder sample for 2019, which has a total of 25 planets that are likely to enter the statistical sample. We find statistical consistency with the previously published 33 planets from the 2018 AnomalyFinder analysis according to an ensemble of five tests. Of the 58 planets from 2018–2019, 23 were newly discovered by AnomalyFinder. Within statistical precision, half of the planets have caustic crossings, while half do not; an equal number of detected planets result from major- and minor-image light-curve perturbations; and an equal number come from KMT prime fields versus subprime fields