Publications by authors named "Ian Porter"

30 Publications

  • Page 1 of 1

Evaluation of Lung Aeration and Respiratory System Mechanics in Obese Dogs Ventilated With Tidal Volumes Based on Ideal vs. Current Body Weight.

Front Vet Sci 2021 1;8:704863. Epub 2021 Oct 1.

Section of Veterinary Clinics and Animal Production, Department of Emergency and Organ Transplantation D.E.O.T., "Aldo Moro" University of Bari, Bari, Italy.

We describe the respiratory mechanics and lung aeration in anesthetized obese dogs ventilated with tidal volumes (VT) based on ideal (VTi) vs. current (VTc) body weight. Six dogs with body condition scores ≥ 8/9 were included. End-expiratory respiratory mechanics and end-expiratory CT-scan were obtained at baseline for each dog. Thereafter, dogs were ventilated with VT 15 ml kg based on VTi and VTc, applied randomly. Respiratory mechanics and CT-scan were repeated at end-inspiration during VTi and VTc. Data analyzed with linear mixed models and reported as mean ± SD or median [range]. Statistical significance < 0.05. The elastance of the lung, chest wall and respiratory system indexed by ideal body weight (IBW) were positively correlated with body fat percentage, whereas the functional residual capacity indexed by IBW was negatively correlated with body fat percentage. At end-expiration, aeration (%) was: hyperaeration 0.03 [0.00-3.35], normoaeration 69.7 [44.6-82.2], hypoaeration 29.3 [13.6-49.4] and nonaeration (1.06% [0.37-6.02]). Next to the diaphragm, normoaeration dropped to 12 ± 11% and hypoaeration increased to 90 ± 8%. No differences in aeration between groups were found at end-inspiration. Airway driving pressure (cm HO) was higher ( = 0.002) during VTc (9.8 ± 0.7) compared with VTi (7.6 ± 0.4). Lung strain was higher ( = 0.014) during VTc (55 ± 21%) than VTi (38 ± 10%). The stress index was higher ( = 0.012) during VTc (SI = 1.07 [0.14]) compared with VTi (SI = 0.93 [0.18]). This study indicates that body fat percentage influences the magnitude of lung, chest wall, and total respiratory system elastance and resistance, as well as functional residual capacity. Further, these results indicate that obese dogs have extensive areas of hypoaerated lungs, especially in caudodorsal regions. Finally, lung strain and airway driving pressure, surrogates of lung deformation, are higher during VTc than during VTi, suggesting that in obese anesthetized dogs, ventilation protocols based on IBW may be advantageous.
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http://dx.doi.org/10.3389/fvets.2021.704863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517180PMC
October 2021

Routine provision of feedback from patient-reported outcome measurements to healthcare providers and patients in clinical practice.

Cochrane Database Syst Rev 2021 Oct 12;10:CD011589. Epub 2021 Oct 12.

Health Services & Policy Research, Exeter Collaboration for Academic Primary Care (APEx), NIHR School for Primary Care Research, NIHR ARC South West Peninsula (PenARC), University of Exeter, Exeter, UK.

Background: Patient-reported outcomes measures (PROMs) assess a patient's subjective appraisal of health outcomes from their own perspective. Despite hypothesised benefits that feedback  on PROMs can support decision-making in clinical practice and improve outcomes, there is uncertainty surrounding the effectiveness of PROMs feedback.

Objectives: To assess the effects of PROMs feedback to patients, or healthcare workers, or both on patient-reported health outcomes and processes of care.

Search Methods: We searched MEDLINE, Embase, CENTRAL, two other databases and two clinical trial registries on 5 October 2020. We searched grey literature and consulted experts in the field.

Selection Criteria: Two review authors independently screened and selected studies for inclusion. We included randomised trials directly comparing the effects on outcomes and processes of care of PROMs feedback to healthcare professionals and patients, or both with the impact of not providing such information.

Data Collection And Analysis: Two groups of two authors independently extracted data from the included studies and evaluated study quality. We followed standard methodological procedures expected by Cochrane and EPOC. We used the GRADE approach to assess the certainty of the evidence. We conducted meta-analyses of the results where possible.

Main Results: We identified 116 randomised trials which assessed the effectiveness of PROMs feedback in improving processes or outcomes of care, or both in a broad range of disciplines including psychiatry, primary care, and oncology. Studies were conducted across diverse ambulatory primary and secondary care settings in North America, Europe and Australasia. A total of 49,785 patients were included across all the studies. The certainty of the evidence varied between very low and moderate. Many of the studies included in the review were at risk of performance and detection bias. The evidence suggests moderate certainty that PROMs feedback probably improves quality of life (standardised mean difference (SMD) 0.15, 95% confidence interval (CI) 0.05 to 0.26; 11 studies; 2687 participants), and leads to an increase in patient-physician communication (SMD 0.36, 95% CI 0.21 to 0.52; 5 studies; 658 participants), diagnosis and notation (risk ratio (RR) 1.73, 95% CI 1.44 to 2.08; 21 studies; 7223 participants), and disease control (RR 1.25, 95% CI 1.10 to 1.41; 14 studies; 2806 participants). The intervention probably makes little or no difference for general health perceptions (SMD 0.04, 95% CI -0.17 to 0.24; 2 studies, 552 participants; low-certainty evidence), social functioning (SMD 0.02, 95% CI -0.06 to 0.09; 15 studies; 2632 participants; moderate-certainty evidence), and pain (SMD 0.00, 95% CI -0.09 to 0.08; 9 studies; 2386 participants; moderate-certainty evidence). We are uncertain about the effect of PROMs feedback on physical functioning (14 studies; 2788 participants) and mental functioning (34 studies; 7782 participants), as well as fatigue (4 studies; 741 participants), as the certainty of the evidence was very low. We did not find studies reporting on adverse effects defined as distress following or related to PROM completion.

Authors' Conclusions: PROM feedback probably produces moderate improvements in communication between healthcare professionals and patients as well as in diagnosis and notation, and disease control, and small improvements to quality of life. Our confidence in the effects is limited by the risk of bias, heterogeneity and small number of trials conducted to assess outcomes of interest. It is unclear whether   many of these improvements are clinically meaningful or sustainable in the long term. There is a need for more high-quality studies in this area, particularly studies which employ cluster designs and utilise techniques to maintain allocation concealment.
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http://dx.doi.org/10.1002/14651858.CD011589.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509115PMC
October 2021

Osteogenesis Imperfecta in Two Finnish Lapphund Puppies.

Vet Med (Auckl) 2021 17;12:177-185. Epub 2021 Jun 17.

Cornell University College of Veterinary Medicine, Department of Biomedical Sciences, Section of Anatomic Pathology, Ithaca, NY, 14853, USA.

Two 8-week-old Finnish Lapphund dogs presented with pain on manipulation, abnormal long bone conformation, retrognathism, and stunted growth compared to their litter mates. Multiple long bone fractures were evident on radiographs. Clinical pathology showed an atypically normal serum alkaline phosphatase activity for dogs this age. Due to poor quality of life, the dogs were humanely euthanized and subjected to a complete necropsy. On necropsy, all bones were soft and easily broken. Histologic examination revealed that the secondary spongiosa was diminished with abnormal bony trabeculae embedded in abundant loose vascular stroma. No Haversian canals were observed and the cortices contained abundant woven bone separated by fibrovascular tissue consistent with the diagnosis of osteogenesis imperfecta (OI). Inbreeding of the sire and female offspring led to a suspicion of recessive inheritance and the particular genetic collagen disorder remains to be identified in this breed.
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http://dx.doi.org/10.2147/VMRR.S308418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216744PMC
June 2021

Integrating Patient Reported Outcome Measures (PROMs) into routine nurse-led primary care for patients with multimorbidity: a feasibility and acceptability study.

Health Qual Life Outcomes 2021 Apr 26;19(1):133. Epub 2021 Apr 26.

Health Services and Policy Research, Exeter Collaboration for Academic Primary Care (APEx), University of Exeter, Magdalen Campus, Smeall Building, Room JS02, Exeter, EX1 2LU, UK.

Background: The use of Patient Reported Outcome Measures (PROMS) in clinical practice has the potential to promote patient-centred care and improve patients' quality of life. Individualized PROMs may be particularly helpful in identifying, prioritizing and monitoring health problems of patients with multimorbidity. We aimed to develop an intervention centred around PROMs feedback as part of Primary Care annual reviews for patients with multimorbidity and evaluate its feasibility and acceptability.

Methods: We developed a nurse-oriented intervention including (a) training of nurses on PROMs; (b) administration to patients with multimorbidity of individualized and standardized PROMS; and (c) feedback to both patients and nurses of PROMs scores and interpretation guidance. We then tailored the intervention to patients with two or more highly prevalent conditions (asthma, COPD, diabetes, heart failure, depression, and hip/knee osteoarthritis) and designed a non-controlled feasibility and acceptability evaluation in a convenience sample of primary care practices (5). PROMs were administered and scores fed back immediately ahead of scheduled annual reviews with nurses. Patients and nurses rated the acceptability of the intervention using with a brief survey including optional free comments. Thematic analysis of qualitative interviews with a sample of participating patients (10) and nurses (4) and of survey free comments was conducted for further in-depth evaluation of acceptability. Feasibility was estimated based on rates of participation and completion.

Results: Out of 68 recruited patients (mean age 70; 47% female), 68 completed the PROMs (100%), received feedback (100%) and confirmed nurse awareness of their scores (100%). Most patients (83%) "agreed"/"strongly agreed" that the PROMs feedback had been useful, a view supported by nurses in 89% of reviews. Thematic analysis of rich qualitative data on PROMS administration, feedback and role in annual reviews indicated that both patients and nurses perceived the intervention as acceptable and promising, emphasizing its comprehensiveness and patient-centredness.

Conclusions: We have developed and tested an intervention focusing on routine PROM assessment of patients with multimorbidity in Primary Care. Preliminary findings support its feasibility and a high degree of acceptability from both patients and nurses. The next step is to conduct a full-scale trial for evaluating the effectiveness of the proposed intervention.
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http://dx.doi.org/10.1186/s12955-021-01748-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074460PMC
April 2021

Evidence That Microorganisms at the Animal-Water Interface Drive Sea Star Wasting Disease.

Front Microbiol 2020 6;11:610009. Epub 2021 Jan 6.

Department of Microbiology, Cornell University, Ithaca, NY, United States.

Sea star wasting (SSW) disease describes a condition affecting asteroids that resulted in significant Northeastern Pacific population decline following a mass mortality event in 2013. The etiology of SSW is unresolved. We hypothesized that SSW is a sequela of microbial organic matter remineralization near respiratory surfaces, one consequence of which may be limited O availability at the animal-water interface. Microbial assemblages inhabiting tissues and at the asteroid-water interface bore signatures of copiotroph proliferation before SSW onset, followed by the appearance of putatively facultative and strictly anaerobic taxa at the time of lesion genesis and as animals died. SSW lesions were induced in by enrichment with a variety of organic matter (OM) sources. These results together illustrate that depleted O conditions at the animal-water interface may be established by heterotrophic microbial activity in response to organic matter loading. SSW was also induced by modestly (∼39%) depleted O conditions in aquaria, suggesting that small perturbations in dissolved O may exacerbate the condition. SSW susceptibility between species was significantly and positively correlated with surface rugosity, a key determinant of diffusive boundary layer thickness. Tissues of SSW-affected individuals collected in 2013-2014 bore δN signatures reflecting anaerobic processes, which suggests that this phenomenon may have affected asteroids during mass mortality at the time. The impacts of enhanced microbial activity and subsequent O diffusion limitation may be more pronounced under higher temperatures due to lower O solubility, in more rugose asteroid species due to restricted hydrodynamic flow, and in larger specimens due to their lower surface area to volume ratios which affects diffusive respiratory potential.
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http://dx.doi.org/10.3389/fmicb.2020.610009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815596PMC
January 2021

Orbital apex syndrome secondary to an orbital sarcoma in a dog.

Can Vet J 2021 01;62(1):27-31

Cornell University - College of Veterinary Medicine, Ithaca, New York, USA.

A 12-year-old castrated male cocker spaniel dog was presented with a 4-week history of left episcleral injection and pawing at the face. Clinical examination findings included left internal and external ophthalmoplegia, left dorsal strabismus, pain opening the mouth, and intermittent amaurosis. Imaging studies revealed a left orbital apex mass with adjacent sphenoid bone lysis and extension into the cranial cavity. A left exenteration was performed and histopathology confirmed an orbital soft tissue sarcoma. Key clinical message: This report describes an orbital tumor causing orbital apex syndrome. This condition should be differentiated from cavernous sinus syndrome as the latter does not course with optic neuropathy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739388PMC
January 2021

Questioning COVID-19 Surface Stability and Fomite Spreading in Three Aeromedical Cases: A Case Series.

Mil Med 2021 07;186(7-8):e832-e835

Department of Aviation Medicine, Navy Medicine Readiness and Training Unit Jacksonville, Jacksonville, FL 32212, USA.

It is well established that coronavirus disease 2019 is primarily transmitted through respiratory droplets, and there is mounting research speculation that it may also be transmitted via fomites. Several studies have shown that the virus can persist on both porous and nonporous surfaces for hours to days, depending upon the material. This article examines three cases of polymerase chain reaction-proven severe acute respiratory syndrome coronavirus 2 infection with several additional individuals meeting CDC close contact criteria. In 1 case, 195 downstream contacts were all tested to prevent a mass outbreak in a deployment posture. Analysis of these contacts yielded only a single positive test, which could be reasonably ascribed to respiratory droplet transmission. While these cases and their contacts ultimately represent a small sample size, we suggest fomite spread may not be a significant means of transmission for severe acute respiratory syndrome coronavirus 2 in real-world operational scenarios.
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http://dx.doi.org/10.1093/milmed/usaa548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798875PMC
July 2021

What Is Your Diagnosis?

J Am Vet Med Assoc 2020 Oct;257(7):697-700

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http://dx.doi.org/10.2460/javma.257.7.697DOI Listing
October 2020

Case Report: COVID-19 Patient With Chief Complaint of Anosmia and Ageusia; a Unique Perspective on Atypical Symptomatology and Management in the Military.

Mil Med 2020 12;185(11-12):e2176-e2179

Department of Aviation Medicine, Navy Medicine Readiness and Training Unit Jacksonville, Building #964 Enterprise Road, Jacksonville FL 32212.

A novel corona virus, severe acute respiratory syndrome coronavirus-2, found in Wuhan, China in December 2019 has since spread to multiple continents and has been implicated in thousands of deaths. This pandemic-causing virus has been initially described (corona virus disease 2019 [COVID-19]) with the presentation of fever, cough, and shortness of breath. The majority of studies published have been conducted on inpatient cases and a shortage of tests has encouraged screening only of patients with classic presentation. A positive COVID-19 case of a healthy military male, with the chief complaint of anosmia and ageusia, instigated local re-evaluation of the screening protocol for possible COVID-19 patients. Multiple studies in Europe have implicated anosmia and ageusia as symptoms associated with COVID-19, and subsequently, anosmia and ageusia have been added to Centers for Disease Control and Prevention screening guidelines as well. There should be a higher index of suspicion when evaluating a patient with high-risk activities, travel, and atypical symptoms. More studies need to be conducted with a healthy outpatient population to further understand this disease and decrease its impact.
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http://dx.doi.org/10.1093/milmed/usaa196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454777PMC
December 2020

Transorbital postcaruncular endoscopic surgery as an alternative to orbital exploratory surgery: A cadaveric study and case report in a dog with an orbital sarcoma.

Vet Surg 2020 Oct 3;49(7):1359-1366. Epub 2020 Jun 3.

Cornell University College of Veterinary Medicine, Ithaca, New York.

Objective: To describe a postcaruncular approach for transorbital endoscopy as an alternative, minimally invasive technique to access the orbital apex.

Study Design: Ex vivo and prospective clinical case report.

Animals: A 12-year-old male castrated cocker spaniel and three cadaver heads (one large breed dolichocephalic, one medium-sized breed mesocephalic, and one small breed brachycephalic).

Methods: Transorbital endoscopy was performed to obtain biopsies of an orbital apex mass by using a postcaruncular approach. A 2.7-mm 30° rigid endoscope fitted with a cystoscope working sheath was used with the aid of a blunt suction-dissector and fluid ingress. This procedure was first performed on three cadavers to assess feasibility and later performed in a clinical case.

Results: By using a transorbital postcaruncular approach, it was possible to visualize and obtain biopsies from structures within the orbital apex with minimal perioperative morbidity. Dissection and expansion of the working space was facilitated with the aid of fluid ingress; however, judicious use of fluids is recommended because secondary orbital edema and chemosis can occur.

Conclusion: Transorbital endoscopy via a postcaruncular approach is feasible.

Clinical Significance: This technique should be considered in cases in which a histological diagnosis is required prior to definitive treatment as a method to obtain biopsy samples of the orbital apex region without major surgical dissection.
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http://dx.doi.org/10.1111/vsu.13446DOI Listing
October 2020

Patient-centred outcomes in lateral elbow tendinopathy: A systematic review of available evidence in UK populations.

Shoulder Elbow 2019 Dec 16;11(6):440-449. Epub 2018 Aug 16.

Health Services and Policy Research Group, University of Exeter, Exeter, UK.

Background: For Patient-Reported Outcome Measures to be useful, they must have evidenced reliability, validity and responsiveness in both the condition and population of interest. The aim of this study is to systematically review the evidence for Patient-Reported Outcome Measures in UK patients with lateral elbow tendinopathy.

Methods: A systematic search was performed in Ovid MEDLINE, Embase and CINAHL. Studies were included if reporting administration of Patient-Reported Outcome Measures in UK populations with lateral elbow tendinopathy. Patient-Reported Outcome Measures characteristics and target populations were assessed using a structured classification system. Patient-Reported Outcome Measures reporting in randomised controlled trials was assessed against Consolidated Standards of Reporting Trials (CONSORT) standards (Patient-Reported Outcome extension).

Results: A total of 16 articles were included. Out of seven different Patient-Reported Outcome Measures, there was evidence of partial validation for five. The assessment of validity, reliability and responsiveness of all Patient-Reported Outcome Measures in lateral elbow tendinopathy UK populations extended to just 20 individual patients. No articles conformed to the CONSORT Patient-Reported Outcome extension standards.

Conclusion: There exists a paucity of data on the psychometrics of Patient-Reported Outcome Measures in UK lateral elbow tendinopathy populations. Without these data, trial design and interpretation are significantly hindered. The high prevalence of this condition and significant volume of studies being conducted into novel treatments highlight the need for this knowledge gap to be resolved.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094069PMC
December 2019

Human Papilloma Virus Vaccination Compliance in a Military Aviation Training Community.

Mil Med 2020 08;185(7-8):e1155-e1160

USS Gerald Ford (CVN 78), FPO AE 09523, VA.

Introduction: Human Papilloma Virus (HPV) vaccination compliance as reported by the CDC in 2011 falls short of a national goal to have 80% of adolescents vaccine-complete by 2020. The Naval Aviation Schools Command, Pensacola, Florida offers a single point of contact for military aviation trainees offering near-complete capture of an HPV vaccine target population. The purpose of this study is to identify baseline HPV vaccination rates among military aviation trainees and whether or not the provision of educational materials at the start of aviation training would increase future HPV vaccination compliance.

Materials And Methods: Approval to conduct this study was obtained from the Institutional Review Board of Naval Medical Center Portsmouth, Virginia. Our population of interest consisted of US Navy and Marine Corps student naval aviators, student naval flight officers (officers), and student enlisted air crew (enlisted) reporting for aviation related duty. A convenience sampling of officer and enlisted student classes checking in for training was performed over a period of 6 months. The first 3 months of students were assigned as the intervention group and the remaining 3 months of students were assigned to the control group. This study was conducted in two parts: (1) an anonymous survey captured cross-sectional data of self-reported HPV vaccine use, and (2) prospective analysis of service members' HPV vaccine rates before and after educational intervention as documented within the military's electronic health record system, Armed Forces Health Longitudinal Technology Application (AHLTA).

Results: AHLTA immunization status was evaluated for 1,164 personnel; 114 (9.8%) were excluded for missing basic vaccination information. Of the remaining 1,050, another 199 (19%) members were excluded as already vaccine complete (evidenced by three shots documented) prior to entry into the study. Within the 199 service members with documented baseline HPV vaccination completion, 197/199 (99%) were officers and 2/199 (0.1%) were enlisted. A total of 851 personnel were included for prospective analysis. Person-time of 100 person years was used and the vaccination rate translates to 16.62/100 person years (95% CI 11.29, 23.59) within intervention vs. 2.96/100 person years (95% CI 0.80, 7.58) within control groups and are significantly different (P = 0.0001). Comparing intervention and control groups, rate ratios = 5.61 (95% CI 2.14, 18.64) and rate differences = 13.66 (95% CI 7.13, 20.19). Among intervention group survey responders who previously reported nonvaccine use, 50.5% reported a change in opinion about obtaining the vaccination, with a higher proportion of enlisted members reporting a change in opinion (62.8% vs. 39.7%, P = 0.0053).

Conclusions: Electronic health records immunizations review noted a baseline vaccine completion rate of 19%. Our study showed a health inequity between enlisted and officers, with officers having 99% of the documented baseline completion rates per AHLTA data. Our prospective analysis noted statistically significant rate differences of 13.66% and rate ratios of 5.61 between intervention and control groups. This analysis of AHLTA data combined with survey response of 50.5% indicating a change in opinion about HPV vaccine use among those who had not yet started vaccine series suggests targeted education would be a low-cost intervention to improve HPV vaccine use rates.
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http://dx.doi.org/10.1093/milmed/usaa024DOI Listing
August 2020

Mandibular Carnassial Tooth Malformations in 6 Dogs-Micro-Computed Tomography and Histology Findings.

Front Vet Sci 2019 17;6:464. Epub 2019 Dec 17.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.

To document the clinical, radiographic, and histological characteristics of mandibular first molar teeth with developmental abnormalities previously attributed to dens invaginatus and enamel pearls in dogs. Affected mandibular first molar teeth from dogs were evaluated grossly and via intraoral radiography. Endodontically and/or periodontally compromised teeth were extracted and subjected to some combination of micro-computed tomography, histopathology, and immunohistochemistry with anti-amelogenin antibody. Six dogs with developmental abnormalities of mandibular first molar teeth were identified, representing 11 affected teeth. The condition was bilateral in 5 dogs, while in 1 dog, only one mandibular first molar tooth was present. Patient weight ranged from 1.7 to 6 kg (median = 4.09 kg). On intraoral radiographs, root convergence or parallelism was noted in 6 of 11 teeth, and root dilaceration was noted in 3 of 11 teeth. Eight teeth required extraction due to periapical lucencies or periodontitis. On micro-CT, the abnormal teeth were characterized by the presence of abnormal, heterogenous hard tissue with beam attenuation characteristics midway between that of enamel and dentin. Enamel fissures were identified in 4 of 8 teeth, while ectopic radicular enamel was identified in 2 of 8 teeth. The abnormal tissue was traversed by channels measuring 20-40 μm in diameter. Channels communicated with the enamel fissures in 2/8 teeth, the furcation in 2/8 teeth and the pulp in 4/8 teeth. The abnormal tissue was frequently surrounded by disorganized dentin. Histologic features of enamel and dentin were absent from the abnormal tissue and immunohistochemistry to detect amelogenin in the abnormal tissue was negative in all samples. The dental abnormalities described here correspond to a previously unrecognized developmental abnormality involving the mandibular first molar teeth in dogs. The developmental origin of the abnormal tissue could not be ascertained, and further investigations are required to determine the mode of formation, origin of the abnormal tissue, and factors associated with development. These developmental abnormalities more closely resemble molar-incisor malformation, rather than dens invaginatus or enamel pearls as described in humans. The authors propose that affected mandibular first molar teeth simply be referred to as having carnassial tooth malformations.
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http://dx.doi.org/10.3389/fvets.2019.00464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951429PMC
December 2019

Soil greenhouse gas emissions from Australian sports fields.

Sci Total Environ 2020 Mar 12;707:134420. Epub 2019 Sep 12.

Applied Chemistry and Environmental Science, School of Science, RMIT University, Melbourne, Vic, Australia.

Managed turf is a potential net source of greenhouse gas (GHG) emissions. While most studies to date have focused on non-sports turf, sports turf may pose an even greater risk of high GHG emissions due to the generally more intensive fertiliser, irrigation and mowing regimes. This study used manual and automated chambers to measure nitrous oxide (NO) and methane (CH) emissions from three sports fields and an area of non-sports turf in southern Australia. Over 213 days (autumn to late spring), the average daily NO emission was 37.6 g N haday at a sports field monitored at least weekly and cumulative NO emission was 2.5 times higher than the adjacent non-sports turf. Less frequent seasonal sampling at two other sports fields showed average NO daily emission ranging from 26 to 90 g N ha day. Management practices associated with periods of relatively high NO emissions were surface renovation and herbicide application. CH emissions at all of the sports fields were generally negligible with the exception of brief periods when soil was waterlogged following heavy rainfall where emissions of up to 1.3 kg C ha day were recorded. Controlled release and nitrification inhibitor containing fertilisers didn't reduce NO, CH or CO emissions relative to urea in a short term experiment. The NO emissions from the sports fields, and even the lower emissions from the non-sports turf, were relatively high compared to other land uses in Australia highlighting the importance of accounting for these emissions at a national level and investigating mitigation practices.
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http://dx.doi.org/10.1016/j.scitotenv.2019.134420DOI Listing
March 2020

A feasibility and acceptability study of an adaptation of the Mindful Self-Compassion program for adult cancer patients.

Palliat Support Care 2020 04;18(2):130-140

Szalmuk Family Psycho-Oncology Research Unit, Cabrini Health, 154 Wattletree Road, Malvern3144, Australia.

Objectives: Psychosocial interventions that mitigate psychosocial distress in cancer patients are important. The primary aim of this study was to examine the feasibility and acceptability of an adaptation of the Mindful Self-Compassion (MSC) program among adult cancer patients. A secondary aim was to examine pre-post-program changes in psychosocial wellbeing.

Method: The research design was a feasibility and acceptability study, with an examination of pre- to post-intervention changes in psychosocial measures. A study information pack was posted to 173 adult cancer patients 6 months-5 years post-diagnosis, with an invitation to attend an eight-week group-based adaptation of the MSC program.

Results: Thirty-two (19%) consented to the program, with 30 commencing. Twenty-seven completed the program (mean age: 62.93 years, SD 14.04; 17 [63%] female), attending a mean 6.93 (SD 1.11) group sessions. There were no significant differences in medico-demographic factors between program-completers and those who did not consent. However, there was a trend toward shorter time since diagnosis in the program-completers group. Program-completers rated the program highly regarding content, relevance to the concerns of cancer patients, and the likelihood of recommending the program to other cancer patients. Sixty-three percent perceived that their mental wellbeing had improved from pre- to post-program; none perceived a deterioration in mental wellbeing. Small-to-medium effects were observed for depressive symptoms, fear of cancer recurrence, stress, loneliness, body image satisfaction, mindfulness, and self-compassion.

Significance Of Results: The MSC program appears feasible and acceptable to adults diagnosed with non-advanced cancer. The preliminary estimates of effect sizes in this sample suggest that participation in the program was associated with improvements in psychosocial wellbeing. Collectively, these findings suggest that there may be value in conducting an adequately powered randomized controlled trial to determine the efficacy of the MSC program in enhancing the psychosocial wellbeing of cancer patients.
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http://dx.doi.org/10.1017/S1478951519000737DOI Listing
April 2020

The Upper Gastrointestinal Cancer Registry (UGICR): a clinical quality registry to monitor and improve care in upper gastrointestinal cancers.

BMJ Open 2019 09 30;9(9):e031434. Epub 2019 Sep 30.

Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Purpose: The Upper Gastrointestinal Cancer Registry (UGICR) was developed to monitor and improve the quality of care provided to patients with upper gastrointestinal cancers in Australia.

Participants: It supports four cancer modules: pancreatic, oesophagogastric, biliary and primary liver cancer. The pancreatic cancer (PC) module was the first module to be implemented, with others being established in a staged approach. Individuals are recruited to the registry if they are aged 18 years or older, have received care for their cancer at a participating public/private hospital or private clinic in Australia and do not opt out of participation.

Findings To Date: The UGICR is governed by a multidisciplinary steering committee that provides clinical governance and oversees clinical working parties. The role of the working parties is to develop quality indicators based on best practice for each registry module, develop the minimum datasets and provide guidance in analysing and reporting of results. Data are captured from existing data sources (population-based cancer incidence registries, pathology databases and hospital-coded data) and manually from clinical records. Data collectors directly enter information into a secure web-based Research Electronic Data Capture (REDCap) data collection platform. The PC module began with a pilot phase, and subsequently, we used a formal modified Delphi consensus process to establish a core set of quality indicators for PC. The second module developed was the oesophagogastric cancer (OGC) module. Results of the 1 year pilot phases for PC and OGC modules are included in this cohort profile.

Future Plans: The UGICR will provide regular reports of risk-adjusted, benchmarked performance on a range of quality indicators that will highlight variations in care and clinical outcomes at a health service level. The registry has also been developed with the view to collect patient-reported outcomes (PROs), which will further add to our understanding of the care of patients with these cancers.
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http://dx.doi.org/10.1136/bmjopen-2019-031434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773358PMC
September 2019

Severe (grade IV) hypersensitivity to iodinated contrast agent in an anesthetized dog.

Can Vet J 2019 Jul;60(7):766-769

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.

An 8-year-old female Labrador dog was anesthetized for contrast-enhanced computed tomography. The dog was sedated with dexmedetomidine and butorphanol and anesthetized with propofol and isoflurane. Upon IV injection of iohexol 350 mg/mL (72 mL), tachycardia, hypotension, and lower airway obstruction developed. Severe hypersensitivity to the contrast agent was suspected. Bronchospasm was treated successfully with epinephrine. Phenylephrine was used for pressure support. While rare, severe hypersensitivity to iodinated contrast agents can occur without evidence of prior exposure.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563883PMC
July 2019

Assessing Patient-Centred Outcomes in Lateral Elbow Tendinopathy: A Systematic Review and Standardised Comparison of English Language Clinical Rating Systems.

Sports Med Open 2019 Mar 20;5(1):10. Epub 2019 Mar 20.

Health Services and Policy Research Group, University of Exeter Medical School, Exeter, UK.

Background: Lateral elbow tendinopathy (LET) is a common condition affecting adults. Although a lack of treatment consensus continues to prompt numerous effectiveness studies, there is a paucity of clear guidance on the choice of outcome measure. Our aim was to undertake a standardised evaluation of the available clinical rating systems that report patient-centred outcomes in LET.

Methods: A systematic review of studies reporting the development, assessment of metric properties and/or use of instruments aiming to quantify LET-specific patient-centred outcome measures was conducted in MEDLINE, Embase and CINAHL (inception-2017) adhering to PRISMA guidance. The evidence for each instrument was independently assessed by two reviewers using the standardised evaluating measures of patient-reported outcomes (EMPRO) method evaluating overall and attribute-specific instrument performance (metric properties and usability). EMPRO scores > 50/100 were considered indicative of high performance.

Results: Out of 7261 references, we identified 105 articles reporting on 15 instruments for EMPRO analysis. Median performance score was 41.6 (range 21.6-72.5), with four instruments meeting high-performance criteria: quick Disabilities of the Arm Shoulder and Hand score (qDASH) (72.5), DASH (66.9), Oxford Elbow Score (OES) (66.6) and Patient-Rated Tennis Elbow Evaluation (PRTEE) (57.0). One hundred seventy-nine articles reported instrument use internationally with DASH as the most frequent (29.7% articles) followed by PRTEE (25.6%), MEPS (15.1%) and qDASH (8.1%). The correlation between frequency of use and performance was r = 0.35 (95%CI - 0.11; 0.83).

Conclusions: This is the first study to provide standardised guidance on the choice of measures for LET. A large number of clinical rating systems are both available and being used for patients with LETs. Robust evidence is available for four measures, the DASH, QDASH, PRTEE and OES. The use of instruments in the literature is only in part explained by instrument performance.
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http://dx.doi.org/10.1186/s40798-019-0183-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426924PMC
March 2019

Nonarticular osseous cyst-like lesions of the intermedioradial carpal bone may be incidental magnetic resonance imaging findings in dogs.

Vet Radiol Ultrasound 2018 Nov 25;59(6):715-720. Epub 2018 Jun 25.

Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853.

As magnetic resonance imaging (MRI) becomes more readily available and more frequently utilized in the assessment of canine carpal lameness, both normal variations and early pathologic conditions must be recognized to optimize patient care and provide accurate diagnosis. On cross sectional studies of the canine carpus, cyst-like lesions have been detected at the dorsolateral aspect of the intermedioradial carpal bone. The cross-sectional imaging and histologic properties of these lesions have not been described. The purpose of this observational study is to evaluate the MRI and histologic features of these cyst-like lesions in a cohort of clinically sound dogs. It was hypothesized that the lesions would show features similar to intraosseous ganglion cysts of the human wrist. Twenty-five cadaveric canine carpi were obtained and a total of 13 lesions were detected on MRI. Based on MRI, six carpi with lesions of varying size and one normal carpus were submitted for histological evaluation. Five of the abnormal carpi had nonarticular cyst-like lesions; one specimen with a positive magnetic resonance image for a cyst-like lesion had no cyst-like lesion on histology. Conspicuity of a medium-size lesion as evaluated on radiographs was poor. Given the presence of these nonarticular cyst-like lesions in a population of clinically sound patients, their clinical importance is uncertain. The development of these lesions may relate to altered mechanics or genetic predispositions, requiring additional study.
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http://dx.doi.org/10.1111/vru.12658DOI Listing
November 2018

Predicting Incident Multimorbidity.

Ann Fam Med 2018 07;16(4):322-329

University of Exeter Medical School, St Luke's Campus, Exeter, Devon, United Kingdom

Purpose: Multimorbidity is associated with adverse outcomes, yet research on the determinants of its incidence is lacking. We investigated which sociodemographic, health, and individual lifestyle (eg, physical activity, smoking behavior, body mass index) characteristics predict new cases of multimorbidity.

Methods: We used data from 4,564 participants aged 50 years and older in the English Longitudinal Study of Aging that included a 10-year follow-up period. Discrete time-to-event (complementary log-log) models were constructed for exploring the associations of baseline characteristics with outcomes between 2002-2003 and 2012-2013 separately for participants with no initial conditions (n = 1,377) developing multimorbidity, any increase in conditions within 10 years regardless of initial conditions, and the impact of individual conditions on incident multimorbidity.

Results: The risks of developing multimorbidity were positively associated with age, and they were greater for the least wealthy, for participants who were obese, and for those who reported the lowest levels of physical activity or an external locus of control (believing that life events are outside of one's control) for all groups regardless of baseline conditions (all linear trends <.05). No significant associations were observed for sex, educational attainment, or social detachment. For participants with any increase in conditions (n = 4,564), a history of smoking was the only additional predictor. For participants with a single baseline condition (n = 1,534), chronic obstructive pulmonary disease (COPD), asthma, and arrhythmia showed the strongest associations with subsequent multimorbidity.

Conclusions: Our findings support the development and implementation of a strategy targeting the prevention of multimorbidity for susceptible groups. This approach should incorporate behavior change addressing lifestyle factors and target health-related locus of control.
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http://dx.doi.org/10.1370/afm.2271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037507PMC
July 2018

Clinical rating systems in elbow research-a systematic review exploring trends and distributions of use.

J Shoulder Elbow Surg 2018 Apr 12;27(4):e98-e106. Epub 2018 Feb 12.

Health Services and Policy Research Group, University of Exeter, Exeter, UK.

Background: Clinical rating systems are used as outcome measures in clinical trials and attempt to gauge the patient's view of his or her own health. The choice of clinical rating system should be supported by its performance against established quality standards.

Methods: A search strategy was developed to identify all studies that reported the use of clinical rating systems in the elbow literature. The strategy was run from inception in Medline Embase and CINHAL. Data extraction identified the date of publication, country of data collection, pathology assessed, and the outcome measure used.

Results: We identified 980 studies that reported clinical rating system use. Seventy-two separate rating systems were identified. Forty-one percent of studies used ≥2 separate measures. Overall, 54% of studies used the Mayo Elbow Performance Score (MEPS). For arthroplasty, 82% used MEPS, 17% used Disabilities of Arm, Shoulder and Hand (DASH), and 7% used QuickDASH. For trauma, 66.7% used MEPS, 32% used DASH, and 23% used the Morrey Score. For tendinopathy, 31% used DASH, 23% used Patient-Rated Tennis Elbow Evaluation (PRTEE), and 13% used MEPS. Over time, there was an increased proportional use of the MEPS, DASH, QuickDASH, PRTEE, and the Oxford Elbow Score.

Conclusions: This study identified a wide choice and usage of clinical rating systems in the elbow literature. Numerous studies reported measures without a history of either a specific pathology or cross-cultural validation. Interpretability and comparison of outcomes is dependent on the unification of outcome measure choice. This was not demonstrated currently.
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http://dx.doi.org/10.1016/j.jse.2017.12.027DOI Listing
April 2018

General practitioner contributions to achieving sustained healthcare for offenders: a qualitative study.

BMC Fam Pract 2018 02 2;19(1):22. Epub 2018 Feb 2.

Plymouth University, Drake Circus, Plymouth, Devon, PL4 8AA, UK.

Background: Offenders frequently have substantial healthcare needs and, like many other socially marginalised groups, often receive healthcare in inverse proportion to their needs. Improved continuity of healthcare over time could contribute to addressing these needs. General Practitioners need to be able to support people with complex social and medical problems, even in systems that are not specifically designed to manage individuals with such degrees of complexity. We aimed to examine offenders' perspectives on factors that contributed to, or worked against, creating and sustaining their access to healthcare.

Methods: From a sample of 200 participants serving community or prison sentences in South West (SW) and South East (SE) England, who were interviewed about their health care experiences as part of the Care for Offenders: Continuity of Access (COCOA) study, we purposively sampled 22 participants for this sub-study, based on service use. These interviews were transcribed verbatim. A thematic analytic approach initially applied 5 a priori codes based on access and different components of continuity. Data were then examined for factors that contributed to achieving and disrupting access and continuity.

Results: Participants described how their own life situations and behaviours contributed to their problems in accessing healthcare and also identified barriers created by existing access arrangements. They also highlighted how some General Practitioners used their initiative and skills to 'workaround' the system, and build positive relationships with them; feeling listened to and building trust were particularly valued, as was clear communication. Limitations faced by General Practitioners included a lack of appropriate services to refer people to, where the offender patients would meet the access criteria, and disagreements regarding medication prescriptions.

Conclusions: General Practitioners can make a positive contribution to supporting access to healthcare for an under-served population by facilitating more flexible and less formal access arrangements, by using their relationship skills, and by problem-solving. General Practitioners should recognise their potential to transform people's experience of healthcare whilst working in imperfect systems, particularly with vulnerable and marginalised groups who have complex medical and social needs.
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http://dx.doi.org/10.1186/s12875-018-0708-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796354PMC
February 2018

Personal well-being networks, social capital and severe mental illness: exploratory study.

Br J Psychiatry 2018 05;212(5):308-317

McPin Foundation,London,UK.

Background: Connectedness is a central dimension of personal recovery from severe mental illness (SMI). Research reports that people with SMI have lower social capital and poorer-quality social networks compared to the general population.AimsTo identify personal well-being network (PWN) types and explore additional insights from mapping connections to places and activities alongside social ties.

Method: We carried out 150 interviews with individuals with SMI and mapped social ties, places and activities and their impact on well-being. PWN types were developed using social network analysis and hierarchical k-means clustering of this data.

Results: Three PWN types were identified: formal and sparse; family and stable; and diverse and active. Well-being and social capital varied within and among types. Place and activity data indicated important contextual differences within social connections that were not found by mapping social networks alone.

Conclusions: Place locations and meaningful activities are important aspects of people's social worlds. Mapped alongside social networks, PWNs have important implications for person-centred recovery approaches through providing a broader understanding of individual's lives and resources.Declaration of interestNone.
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http://dx.doi.org/10.1192/bjp.bp.117.203950DOI Listing
May 2018

Nitrification inhibitors can increase post-harvest nitrous oxide emissions in an intensive vegetable production system.

Sci Rep 2017 03 7;7:43677. Epub 2017 Mar 7.

Institute for Future Environments, Queensland University of Technology, Brisbane, QLD 4000, Australia.

To investigate the effect of nitrification inhibitors (NIs) 3,4-dimethylpyrazole phosphate (DMPP) and 3-methylpyrazole 1,2,4-triazole (3MP + TZ), on NO emissions and yield from a typical vegetable rotation in sub-tropical Australia we monitored soil NO fluxes continuously over an entire year using an automated greenhouse gas measurement system. The temporal variation of NO fluxes showed only low emissions over the vegetable cropping phases, but significantly higher emissions were observed post-harvest accounting for 50-70% of the annual emissions. NIs reduced NO emissions by 20-60% over the vegetable cropping phases; however, this mitigation was offset by elevated NO emissions from the NIs treatments over the post-harvest fallow period. Annual NO emissions from the conventional fertiliser, the DMPP treatment, and the 3MP + TZ treatment were 1.3, 1.1 and 1.6 (sem = 0.2) kg-N ha year, respectively. This study highlights that the use of NIs in vegetable systems can lead to elevated NO emissions by storing N in the soil profile that is available to soil microbes during the decomposition of the vegetable residues. Hence the use of NIs in vegetable systems has to be treated carefully and fertiliser rates need to be adjusted to avoid an oversupply of N during the post-harvest phase.
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http://dx.doi.org/10.1038/srep43677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339787PMC
March 2017

Pathologic response to neoadjuvant treatment in locally advanced rectal cancer and impact on outcome.

J Gastrointest Oncol 2016 Aug;7(4):603-8

Department of Colorectal Surgery, Alfred hospital, 55 Commercial Road, Melbourne, Victoria 3004, Australia.

Background: Downstaging and pathologic complete response (pCR) after chemoradiotherapy (CRT) may improve progression-free survival and overall survival (OS) after curative therapy of locally advanced adenocarcinoma of rectum. The purpose of this study is to evaluate the pathologic response subsequent to neoadjuvant chemoradiation in locally advanced rectal adenocarcinoma and any impact of response on oncological outcome [disease-free survival (DFS), OS].

Methods: A total of 127 patients with histologically-proven rectal adenocarcinoma, locally advanced, were treated with preoperative radiotherapy and concurrent 5-fluorouracil (5 FU), and followed by curative surgery. Pathologic response to neoadjuvant treatment was evaluated by comparing pathologic TN (tumour and nodal) staging (yp) with pre-treatment clinical staging. DFS and OS were compared in patients with: pCR, partial pathologic response and no response to neoadjuvant therapy.

Results: 14.96% (19 patients) had a pCR, 58.27% [74] showed downstaging and 26.77% [34] had no change in staging. At follow-up (range, 4-9 years, median 6 years 2 months or 74 months), 17.32% [22] showed recurrence: 15.74% [20] distant metastasis, 1.57% [2] pelvic failure. 10.5% [2] of the patients with pCR showed distant metastasis, none showed local recurrence. In the downstaged group, nine developed distant failure and two had local recurrence (14.86%). Distant failure was seen in 26.47% [9] of those with no response to neoadjuvant treatment. DFS and OS rates for all groups were 82.67% and 88.97% respectively. Patients with pCR showed 89.47% DFS and 94.7% OS. In partial responders, DFS was 85.1% and OS was 90.5%. In non-responders, DFS and OS were 73.5% and 82.3% respectively. Patients with pCR had a significantly greater probability of DFS and OS than non-responders. Rectal cancer-related death was 11.02% [14]: one patient (5.26%) with pCR, 9.47% [7] in the downstaged group and 17.64% [6] of non-responders.

Conclusions: The majority of patients showed some response to neoadjuvant treatment. Findings of this study indicate tumour response to neoadjuvant CRT improves the long-term outcome, with a better result in patients with pCR.
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http://dx.doi.org/10.21037/jgo.2016.05.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963368PMC
August 2016

Framework and guidance for implementing patient-reported outcomes in clinical practice: evidence, challenges and opportunities.

J Comp Eff Res 2016 08 18;5(5):507-19. Epub 2016 Jul 18.

Health Services & Policy Research Group, Exeter Collaboration for Academic Primary Care (APEx) (Person centerd Care), University of Exeter Medical School, University of Exeter, Exeter, UK.

Patient-reported outcomes (PROs) are reports of the status of a patient's health condition that come directly from the patient. While PRO measures are a well-developed technology with robust standards in research, their use for informing healthcare decisions is still poorly understood. We review relevant examples of their application in the provision of healthcare and examine the challenges associated with implementing PROs in clinical settings. We evaluate evidence for their use and examine barriers to their uptake, and present an evidence-based framework for the successful implementation of PROs in clinical practice. We discuss current and future developments for the use of PROs in clinical practice, such as individualized measurement and computer-adaptive testing.
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http://dx.doi.org/10.2217/cer-2015-0014DOI Listing
August 2016

Complete Pathological Response After Neoadjuvant Long-Course Chemoradiotherapy for Rectal Cancer and Its Relationship to the Degree of T3 Mesorectal Invasion.

Dis Colon Rectum 2016 May;59(5):361-8

1 Cabrini Monash University Department of Surgery, Cabrini Hospital, Malvern, Victoria, Australia 2 Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Victoria, Australia 3 William Buckland Radiotherapy Centre, The Alfred Hospital, Department of Surgery, Monash University Central Clinical School, Melbourne, Victoria, Australia 4 Monash Department of Clinical Epidemiology, Cabrini Hospital, Malvern, Victoria, Australia.

Background: Many studies have shown significantly improved outcomes (reduced local recurrence and improved overall survival) for patients achieving a complete pathological response from neoadjuvant chemoradiotherapy.

Objective: This study aimed to document the complete pathological response rate and outcomes in patients receiving preoperative long-course chemoradiotherapy stratified for the extent of T3 mesorectal invasion measured on preoperative imaging.

Design: This is a retrospective study of prospectively collected data, of patients with rectal cancer in the Cabrini Monash University Department of Surgery colorectal neoplasia database, incorporating data from Cabrini Hospital and The Alfred Hospital, identifying patients entered between January 2010 and June 2014.

Patients And Settings: One hundred eighteen patients with T3 rectal cancer met the selection criteria for the study; 26 achieved complete pathological response (22%).

Main Outcome Measures: Outcomes in terms of complete pathological response and oncological outcomes such as disease-free and overall survival were analyzed.

Results: Patients with complete pathological response had significantly less preoperative invasion than those with no complete pathological response (p < 0.001). Depth of invasion was the only variable associated with complete pathological response (p < 0.002), and the likelihood of complete pathological response decreased by 35% for every millimeter of invasion. Complete pathological response was associated with increased disease-free survival (p = 0.018) and a lower risk of cancer progression (p = 0.046). Depth of invasion was associated with an increased risk of death after surgery; HR increased by 1.07 (95% CI, 1.00-1.15) for each 1-mm increase in invasion.

Limitations: This was a retrospective study with the usual limitations, although these were minimized through the use of a clinician-driven prospective database.

Conclusions: The smaller the degree of T3 invasion, the higher the chance of achieving complete pathological response (up to 35%), which is associated with improved disease-free and overall survival. A higher complete pathological response rate is observed in early T3 disease in comparison with more extensive T3 invasion.
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http://dx.doi.org/10.1097/DCR.0000000000000564DOI Listing
May 2016

Identification of an anchor residue for CheA-CheY interactions in the chemotaxis system of Escherichia coli.

J Bacteriol 2011 Aug 3;193(15):3894-903. Epub 2011 Jun 3.

Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.

Transfer of a phosphoryl group from autophosphorylated CheA (P-CheA) to CheY is an important step in the bacterial chemotaxis signal transduction pathway. This reaction involves CheY (i) binding to the P2 domain of P-CheA and then (ii) acquiring the phosphoryl group from the P1 domain. Crystal structures indicated numerous side chain interactions at the CheY-P2 binding interface. To investigate the individual contributions of the P2 side chains involved in these contacts, we analyzed the effects of eight alanine substitution mutations on CheA-CheY binding interactions. An F214A substitution in P2 caused ∼1,000-fold reduction in CheA-CheY binding affinity, while Ala substitutions at other P2 positions had small effects (E171A, E178A, and I216A) or no detectable effects (H181A, D202A, D207A, and C213A) on binding affinity. These results are discussed in relation to previous in silico predictions of hot-spot and anchor positions at the CheA-CheY interface. We also investigated the consequences of these mutations for chemotaxis signal transduction in living cells. CheA(F214A) was defective in mediating localization of CheY-YFP to the large clusters of signaling proteins that form at the poles of Escherichia coli cells, while the other CheA variants did not differ from wild-type (wt) CheA (CheA(wt)) in this regard. In our set of mutants, only CheA(F214A) exhibited a markedly diminished ability to support chemotaxis in motility agar assays. Surprisingly, however, in FRET assays that monitored receptor-regulated production of phospho-CheY, CheA(F214A) (and each of the other Ala substitution mutants) performed just as well as CheA(wt). Overall, our findings indicate that F214 serves as an anchor residue at the CheA-CheY interface and makes an important contribution to the binding energy in vitro and in vivo; however, loss of this contribution does not have a large negative effect on the overall ability of the signaling pathway to modulate P-CheY levels in response to chemoattractants.
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http://dx.doi.org/10.1128/JB.00426-11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3147499PMC
August 2011

Does chemotherapy improve survival in high-risk stage I and II Merkel cell carcinoma of the skin?

Int J Radiat Oncol Biol Phys 2006 Jan 25;64(1):114-9. Epub 2005 Aug 25.

University of Queensland, Southern Zone Radiation Oncology, Raymond Tce, South Brisbane, QLD, Australia.

Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy in improving survival was evaluated by comparison of a matched set of historic control subjects with patients treated in a prospective Phase II study that used synchronous chemotherapy and radiation and adjuvant chemotherapy.

Patients And Methods: Patients were included in the analysis if they had disease localized to the primary site and nodes, and they were required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, or gross residual disease after surgery. All patients who received chemotherapy were treated in a standardized fashion as part of a Phase II study (Trans-Tasman Radiation Oncology Group TROG 96:07) from 1997 to 2001. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (AUC 4.5) and etoposide, 80 mg/m(2) i.v. on Days 1 to 3, were given in Weeks 1, 4, 7, and 10. The historic group represents a single institution's experience from 1988 to 1996 and was treated with surgery and radiation alone, and patients were included if they fulfilled the eligibility criteria of TROG 96:07. Patients with occult cutaneous disease were not included for the purpose of this analysis. Because of imbalances in the prognostic variables between the two treatment groups, comparisons were made by application of Cox's proportional hazard modeling. Overall survival, disease-specific survival, locoregional control, and distant control were used as endpoints for the study.

Results: Of the 102 patients who had high-risk Stage I and II disease, 40 were treated with chemotherapy (TROG 96:07) and 62 were treated without chemotherapy (historic control subjects). When Cox's proportional hazards modeling was applied, the only significant factors for overall survival were recurrent disease, age, and the presence of residual disease. For disease-specific survival, recurrent disease was the only significant factor. Primary site on the lower limb had an adverse effect on locoregional control. For distant control, the only significant factor was residual disease.

Conclusions: The multivariate analysis suggests chemotherapy has no effect on survival, but because of the wide confidence limits, a chemotherapy effect cannot be excluded. A study of this size is inadequately powered to detect small improvements in survival, and a larger randomized study remains the only way to truly confirm whether chemotherapy improves the results in high-risk MCC.
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http://dx.doi.org/10.1016/j.ijrobp.2005.04.042DOI Listing
January 2006
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