Durability of bioprosthetic aortic valves in patients under the age of 60 years - Rationale and design of the international INDURE registry

Background: There is an ever-growing number of patients requiring aortic valve replacement (AVR). Limited data is available on the long-term outcomes and structural integrity of bioprosthetic valves in younger patients undergoing surgical AVR. Methods: The INSPIRIS RESILIA Durability Registry (INDURE) is a prospective, open-label, multicentre, international registry with a follow-up of 5 years to assess clinical outcomes of patients younger than 60 years who undergo surgical AVR using the INSPIRIS RESILIA aortic valve. INDURE will be conducted across 20-22 sites in Europe and Canada and intends to enrol minimum of 400 patients. Patients will be included if they are scheduled to undergo AVR with or without concomitant root replacement and/or coronary bypass surgery. The primary objectives are to 1) determine VARC-2 defined time-related valve safety at one-year (depicted as freedom from events) and 2) determine freedom from stage 3 structural valve degeneration (SVD) presenting as morphological abnormalities and severe haemodynamic valve degeneration at 5 years. Secondary objectives include the assessment of the haemodynamic performance of the valve, all stages of SVD, potential valve-in-valve procedures, clinical outcomes (in terms of New York Heart Association [NYHA] function class and freedom from valve-related rehospitalisation) and change in patient quality-of-life. Discussion: INDURE is a prospective, multicentre registry in Europe and Canada, which will provide much needed data on the long-term performance of bioprosthetic valves in general and the INSPIRIS RESILIA valve in particular. The data may help to gather a deeper understanding of the longevity of bioprosthetic valves and may expand the use of bioprosthetic valves in patients under the age of 60 years. Trial registration: ClinicalTrials.gov identifier: NCT03666741 (registration received September, 12th, 2018)

Does inter-vertebral range of motion increase after spinal manipulation? A prospective cohort study.

Background: Spinal manipulation for nonspecific neck pain is thought to work in part by improving inter-vertebral range of motion (IV-RoM), but it is difficult to measure this or determine whether it is related to clinical outcomes. Objectives: This study undertook to determine whether cervical spine flexion and extension IV-RoM increases after a course of spinal manipulation, to explore relationships between any IV-RoM increases and clinical outcomes and to compare palpation with objective measurement in the detection of hypo-mobile segments. Method: Thirty patients with nonspecific neck pain and 30 healthy controls matched for age and gender received quantitative fluoroscopy (QF) screenings to measure flexion and extension IV-RoM (C1-C6) at baseline and 4-week follow-up between September 2012-13. Patients received up to 12 neck manipulations and completed NRS, NDI and Euroqol 5D-5L at baseline, plus PGIC and satisfaction questionnaires at follow-up. IV-RoM accuracy, repeatability and hypo-mobility cut-offs were determined. Minimal detectable changes (MDC) over 4 weeks were calculated from controls. Patients and control IV-RoMs were compared at baseline as well as changes in patients over 4 weeks. Correlations between outcomes and the number of manipulations received and the agreement (Kappa) between palpated and QF-detected of hypo-mobile segments were calculated. Results: QF had high accuracy (worst RMS error 0.5o) and repeatability (highest SEM 1.1o, lowest ICC 0.90) for IV-RoM measurement. Hypo-mobility cut offs ranged from 0.8o to 3.5o. No outcome was significantly correlated with increased IV-RoM above MDC and there was no significant difference between the number of hypo-mobile segments in patients and controls at baseline or significant increases in IV-RoMs in patients. However, there was a modest and significant correlation between the number of manipulations received and the number of levels and directions whose IV-RoM increased beyond MDC (Rho=0.39, p=0.043). There was also no agreement between palpation and QF in identifying hypo-mobile segments (Kappa 0.04-0.06). Conclusions: This study found no differences in cervical sagittal IV-RoM between patients with non-specific neck pain and matched controls. There was a modest dose-response relationship between the number of manipulations given and number of levels increasing IV-RoM - providing evidence that neck manipulation has a mechanical effect at segmental levels. However, patient-reported outcomes were not related to this

Research on nonlinear optical materials: an assessment

The seven papers making up this assessment are based on the Workshop on Nonlinear Optical Materials held in April 1986

Systematically missing confounders in individual participant data meta-analysis of observational cohort studies.

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohort

Improving the content validity of the mixed methods appraisal tool: a modified e-Delphi study

Objective The mixed methods appraisal tool (MMAT) was developed for critically appraising different study designs. This study aimed to improve the content validity of three of the five categories of studies in the MMAT by identifying relevant methodological criteria for appraising the quality of qualitative, survey, and mixed methods studies. Study Design and Setting First, we performed a literature review to identify critical appraisal tools and extract methodological criteria. Second, we conducted a two-round modified e-Delphi technique. We asked three method-specific panels of experts to rate the relevance of each criterion on a five-point Likert scale. Results A total of 383 criteria were extracted from 18 critical appraisal tools and a literature review on the quality of mixed methods studies, and 60 were retained. In the first and second rounds of the e-Delphi, 73 and 56 experts participated, respectively. Consensus was reached for six qualitative criteria, eight survey criteria, and seven mixed methods criteria. These results led to modifications of eight of the 11 MMAT (version 2011) criteria. Specifically, we reformulated two criteria, replaced four, and removed two. Moreover, we added six new criteria. Conclusion Results of this study led to improve the content validity of this tool, revise it, and propose a new version (MMAT version 2018)

Chronic elevation of pulmonary microvascular pressure in chronic heart failure reduces bi-directional pulmonary fluid flux

Aims. Chronic heart failure leads to pulmonary vascular remodelling and thickening of the alveolar–capillary barrier. We examined whether this protective effect may slow resolution of pulmonary oedema consistent with decreased bi-directional fluid flux. Methods and results. Seven weeks following left coronary artery ligation, we measured both fluid flux during an acute rise in left atrial pressure (n = 29) and intrinsic alveolar fluid clearance (n = 45) in the isolated rat lung. Chronic elevation of pulmonary microvascular pressure prevented pulmonary oedema and decreased lung compliance when left atrial pressure was raised to 20 cmH2O, and was associated with reduced expression of endothelial aquaporin 1 (P = 0.03). However, no other changes were found in mediators of fluid flux or cellular fluid channels. In isolated rat lungs, chronic LV dysfunction (LV end-diastolic pressure and infarct circumference) was also inversely related to alveolar fluid clearance (P ≤ 0.001). The rate of pulmonary oedema reabsorption was estimated by plasma volume expansion in eight patients with a previous clinical history of chronic heart failure and eight without, who presented with acute pulmonary oedema. Plasma volume expansion was reduced at 24 h in those with chronic heart failure (P = 0.03). Conclusions. Chronic elevation of pulmonary microvascular pressure in CHF leads to decreased intrinsic bi-directional fluid flux at the alveolar–capillary barrier. This adaptive response defends against alveolar flooding, but may delay resolution of alveolar oedema.A National Health and Medical Research Council (NHMRC) grant (#375129); Australian and New Zealand College of Anaesthetists (ANZCA) grant (#08/020); the Flinders Medical Centre Foundation

Durability of bioprosthetic aortic valves in patients under the age of 60 years - Rationale and design of the international INDURE registry

Background: There is an ever-growing number of patients requiring aortic valve replacement (AVR). Limited data is available on the long-term outcomes and structural integrity of bioprosthetic valves in younger patients undergoing surgical AVR. Methods: The INSPIRIS RESILIA Durability Registry (INDURE) is a prospective, open-label, multicentre, international registry with a follow-up of 5 years to assess clinical outcomes of patients younger than 60 years who undergo surgical AVR using the INS

Cost-effectiveness of general practice care for low back pain: a systematic review

Care from a general practitioner (GP) is one of the most frequently utilised healthcare services for people with low back pain and only a small proportion of those with low back pain who seek care from a GP are referred to other services. The aim of this systematic review was to evaluate the evidence on cost-effectiveness of GP care in non-specific low back pain. We searched clinical and economic electronic databases, and the reference list of relevant systematic reviews and included studies to June 2010. Economic evaluations conducted alongside randomised controlled trials with at least one GP care arm were eligible for inclusion. Two reviewers independently screened search results and extracted data. Eleven studies were included; the majority of which conducted a cost-effectiveness or cost-utility analysis. Most studies investigated the cost-effectiveness of usual GP care. Adding advice, education and exercise, or exercise and behavioural counselling, to usual GP care was more cost-effective than usual GP care alone. Clinical rehabilitation and/or occupational intervention, and acupuncture were more cost-effective than usual GP care. One study investigated the cost-effectiveness of guideline-based GP care, and found that adding exercise and/or spinal manipulation was more cost-effective than guideline-based GP care alone. In conclusion, GP care alone did not appear to be the most cost-effective treatment option for low back pain. GPs can improve the cost-effectiveness of their treatment by referring their patients for additional services, such as advice and exercise, or by providing the services themselves

Help-seeking behaviour among people living with chronic hip or knee pain in the community

<p>Abstract</p> <p>Background</p> <p>A large proportion of people living with hip or knee pain do not consult health care professionals. Pain severity is often believed to be the main reason for help seeking in this population; however the evidence for this is contradictory. This study explores the importance of several potential risk factors on help seeking across different practitioner groups, among adults living with chronic hip or knee pain in a large community sample.</p> <p>Methods</p> <p>Health care utilization, defined as having seen a family doctor (GP) during the past 12 months; or an allied health professional (AHP) or alternative therapist during the past 3 months, was assessed in a community based sample aged 35 or over and reporting pain in hip or knee. Adjusted odds ratios were determined for social deprivation, rurality, pain severity, mobility, anxiety/depression, co-morbidities, and body mass index.</p> <p>Results</p> <p>Of 1119 persons reporting hip or knee pain, 52% had pain in both sites.</p> <p>Twenty-five percent of them had seen a doctor only, 3% an AHP only, and 4% an alternative therapist only. Thirteen percent had seen more than one category of health care professionals, and 55% had not seen any health care professional. In the multivariate model, factors associated with consulting a GP were mobility problems (OR 2.62 (1.64-4.17)), urban living (OR 2.40 (1.14-5.04) and pain severity (1.28 (1.13-1.44)). There was also some evidence that obesity was associated with increased consultation (OR 1.72 (1.00-2.93)). Factors were similar for consultation with a combination of several health care professionals. In contrast, seeing an alternative therapist was negatively associated with pain severity, anxiety and mobility problems (adjusting for age and sex).</p> <p>Conclusion</p> <p>Disability appears to be a more important determinant of help-seeking than pain severity or anxiety and depression, for adults with chronic pain in hip or knee. The determinants of seeking help from alternative practitioners are different from determinants of consulting GPs, AHPs or a combination of different health care providers.</p