Interior Health

BACKGROUND: Scoping studies are increasingly common for broadly searching the literature on a specific topic, yet researchers lack an agreed-upon definition of and framework for the methodology. In 2005, Arksey and O'Malley offered a methodological framework for conducting scoping studies. In their subsequent work, Levac et al. responded to Arksey and O'Malley's call for advances to their framework. Our paper builds on this collective work to further enhance the methodology. DISCUSSION: This paper begins with a background on what constitutes a scoping study, followed by a discussion about four primary subjects: (1) the types of questions for which Arksey and O'Malley's framework is most appropriate, (2) a contribution to the discussion aimed at enhancing the six steps of Arskey and O'Malley's framework, (3) the strengths and challenges of our experience working with Arksey and O'Malley's framework as a large, inter-professional team, and (4) lessons learned. Our goal in this paper is to add to the discussion encouraged by Arksey and O'Malley to further enhance this methodology. SUMMARY: Performing a scoping study using Arksey and O'Malley's framework was a valuable process for our research team even if how it was useful was unexpected. Based on our experience, we recommend researchers be aware of their expectations for how Arksey and O'Malley's framework might be useful in relation to their research question, and remain flexible to clarify concepts and to revise the research question as the team becomes familiar with the literature. Questions portraying comparisons such as between interventions, programs, or approaches seem to be the most suitable to scoping studies. We also suggest assessing the quality of studies and conducting a trial of the method before fully embarking on the charting process in order to ensure consistency. The benefits of engaging a large, inter-professional team such as ours throughout every stage of Arksey and O'Malley's framework far exceed the challenges and we recommend researchers consider the value of such a team. The strengths include breadth and depth of knowledge each team member brings to the study and time efficiencies. In our experience, the most significant challenges presented to our team were those related to consensus and resource limitations. Effective communication is key to the success of a large group. We propose that by clarifying the framework, the purposes of scoping studies are attainable and the definition is enriched.

Abstract Primary resistance to androgen receptor (AR)–directed therapies in metastatic castration-resistant prostate cancer (mCRPC) is poorly understood. We randomized 202 patients with treatment-naïve mCRPC to abiraterone or enzalutamide and performed whole-exome and deep targeted 72-gene sequencing of plasma cell-free DNA prior to therapy. For these agents, which have never been directly compared, time to progression was similar. Defects in BRCA2 and ATM were strongly associated with poor clinical outcomes independently of clinical prognostic factors and circulating tumor DNA abundance. Somatic alterations in TP53, previously linked to reduced tumor dependency on AR signaling, were also independently associated with rapid resistance. Although detection of AR amplifications did not outperform standard prognostic biomarkers, AR gene structural rearrangements truncating the ligand binding domain were identified in several patients with primary resistance. These findings establish genomic drivers of resistance to first-line AR-directed therapy in mCRPC and identify potential minimally invasive biomarkers. Significance: Leveraging plasma specimens collected in a large randomized phase II trial, we report the relative impact of common circulating tumor DNA alterations on patient response to the most widely used therapies for advanced prostate cancer. Our findings suggest that liquid biopsy analysis can guide the use of AR-targeted therapy in general practice. Cancer Discov; 8(4); 444–57. ©2018 AACR. See related commentary by Jayaram et al., p. 392. This article is highlighted in the In This Issue feature, p. 371

OBJECTIVES: To describe the process and outcomes of using a new evidence base to develop scientific guidelines that specify the type and minimum dose of exercise necessary to improve fitness and cardiometabolic health in adults with spinal cord injury (SCI). SETTING: International. METHODS: Using Appraisal of Guidelines, Research and Evaluation (AGREE) II reporting criteria, steps included (a) determining the guidelines' scope; (b) conducting a systematic review of relevant literature; (c) holding three consensus panel meetings (European, Canadian and International) to formulate the guidelines; (d) obtaining stakeholder feedback; and (e) process evaluation by an AGREE II consultant. Stakeholders were actively involved in steps (c) and (d). RESULTS: For cardiorespiratory fitness and muscle strength benefits, adults with a SCI should engage in at least 20 min of moderate to vigorous intensity aerobic exercise 2 times per week AND 3 sets of strength exercises for each major functioning muscle group, at a moderate to vigorous intensity, 2 times per week (strong recommendation). For cardiometabolic health benefits, adults with a SCI are suggested to engage in at least 30 min of moderate to vigorous intensity aerobic exercise 3 times per week (conditional recommendation). CONCLUSIONS: Through a systematic, rigorous, and participatory process involving international scientists and stakeholders, a new exercise guideline was formulated for cardiometabolic health benefits. A previously published SCI guideline was endorsed for achieving fitness benefits. These guidelines represent an important step toward international harmonization of exercise guidelines for adults with SCI, and a foundation for developing exercise policies and programs for people with SCI around the world.

Coronary artery disease (CAD) is the most common health problem worldwide and remains the leading cause of morbidity and mortality. Over the past decade, it has become clear that the inhabitants of our gut, the gut microbiota, play a vital role in human metabolism, immunity, and reactions to diseases, including CAD. Although correlations have been shown between CAD and the gut microbiota, demonstration of potential causal relationships is much more complex and challenging. In this review, we will discuss the potential direct and indirect causal roots between gut microbiota and CAD development via microbial metabolites and interaction with the immune system. Uncovering the causal relationship of gut microbiota and CAD development can lead to novel microbiome-based preventative and therapeutic interventions. However, an interdisciplinary approach is required to shed light on gut bacterial-mediated mechanisms (e.g., using advanced nanomedicine technologies and incorporation of demographic factors such as age, sex, and ethnicity) to enable efficacious and high-precision preventative and therapeutic strategies for CAD.

The 2018 update of the Canadian Stroke Best Practice Recommendations for Acute Stroke Management, 6th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by healthcare providers and system planners caring for persons with very recent symptoms of acute stroke or transient ischemic attack. The recommendations are intended for use by a interdisciplinary team of clinicians across a wide range of settings and highlight key elements involved in prehospital and Emergency Department care, acute treatments for ischemic stroke, and acute inpatient care. The most notable changes included in this 6th edition are the renaming of the module and its integration of the formerly separate modules on prehospital and emergency care and acute inpatient stroke care. The new module, Acute Stroke Management: Prehospital, Emergency Department, and Acute Inpatient Stroke Care is now a single, comprehensive module addressing the most important aspects of acute stroke care delivery. Other notable changes include the removal of two sections related to the emergency management of intracerebral hemorrhage and subarachnoid hemorrhage. These topics are covered in a new, dedicated module, to be released later this year. The most significant recommendation updates are for neuroimaging; the extension of the time window for endovascular thrombectomy treatment out to 24 h; considerations for treating a highly selected group of people with stroke of unknown time of onset; and recommendations for dual antiplatelet therapy for a limited duration after acute minor ischemic stroke and transient ischemic attack. This module also emphasizes the need for increased public and healthcare provider's recognition of the signs of stroke and immediate actions to take; the important expanding role of paramedics and all emergency medical services personnel; arriving at a stroke-enabled Emergency Department without delay; and launching local healthcare institution code stroke protocols. Revisions have also been made to the recommendations for the triage and assessment of risk of recurrent stroke after transient ischemic attack/minor stroke and suggested urgency levels for investigations and initiation of management strategies. The goal of this updated guideline is to optimize stroke care across Canada, by reducing practice variations and reducing the gap between current knowledge and clinical practice.

PURPOSE: To evaluate the safety and efficacy of oral everolimus, a mammalian target of rapamycin (mTOR) inhibitor, in two different schedules in minimally pretreated patients with metastatic breast cancer and to explore for possible biologic correlates of response. PATIENTS AND METHODS: Patients who received no or one prior chemotherapy regimen for metastatic breast cancer were entered onto this multicenter, noncomparative, randomized phase II study of everolimus 10 mg daily versus 70 mg weekly; the multinomial end points of response and progression were evaluated at 8 weeks. A two-stage accrual design was used, with 15 evaluable patients in each schedule in stage 1. Only daily therapy met criteria for continuing, and another 15 patients were added. pAKT, PTEN, carbonic anhydrase 9, estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were evaluated for possible correlation with response. RESULTS: The most common drug-related toxicities were fatigue, rash, anorexia, diarrhea, stomatitis, cough, and pneumonitis. Pneumonitis occurred at higher than expected rates and seemed to be schedule dependent, with the highest incidence on the daily schedule. Response rate with daily therapy was 12% (95% CI, 3.4% to 28.2%) compared with 0% (95% CI, 0.0% to 20.6%) for weekly therapy. Twenty-seven percent of patients on daily therapy discontinued treatment compared with 13% on weekly therapy (16% v 6% with pneumonitis, respectively). No biologic correlates of response could be identified, although there were trends favoring benefit in ER-positive and HER2-negative metastatic breast cancer. CONCLUSION: Oral everolimus has activity in metastatic breast cancer that is schedule dependent. Daily therapy with 10 mg is worthy of further study in this patient population.

Cardiovascular (CV) issues after spinal cord injury (SCI) are of paramount importance considering they are the leading cause of death in this population. Disruption of autonomic pathways leads to a highly unstable CV system, with impaired blood pressure (BP) and heart rate regulation. In addition to low resting BP, on a daily basis the majority of those with SCI suffer from transient episodes of aberrantly low and high BP (termed orthostatic hypotension and autonomic dysreflexia, respectively). In fact, autonomic issues, including resolution of autonomic dysreflexia, are frequently ranked by individuals with high-level SCI to be of greater priority than walking again. Owing to a combination of these autonomic disturbances and a myriad of lifestyle factors, the pernicious process of CV disease is accelerated post-SCI. Unfortunately, these secondary consequences of SCI are only beginning to receive appropriate clinical attention. Immediately after high-level SCI, major CV abnormalities present in the form of neurogenic shock. After subsiding, new issues related to BP instability arise, including orthostatic hypotension and autonomic dysreflexia. This review describes autonomic control over the CV system before injury and the mechanisms underlying CV abnormalities post-SCI, while also detailing the end-organ consequences, including those of the heart, as well as the systemic and cerebral vasculature. The tertiary impact of CV dysfunction will also be discussed, such as the potential impediment of rehabilitation, and impaired cognitive function. In the recent past, our understanding of autonomic dysfunctions post-SCI has been greatly enhanced; however, it is vital to further develop our understanding of the long-term consequences of these conditions, which will equip us to better manage CV disease morbidity and mortality in this population.

OBJECTIVES: To review the diagnosis and management of overwhelming postsplenectomy infection and to discuss various preventative measures. DATA SOURCES: Data used to prepare this article were drawn from published articles and work in progress. STUDY SELECTION: Articles were selected for relevance to the subject after location by a MEDLINE key word search. DATA EXTRACTION: The literature was reviewed to summarize the etiology and pathophysiology of postsplenectomy sepsis. Preventative strategies were outlined with a particular emphasis on education, immunoprophylaxis, and chemoprophylaxis. DATA SYNTHESIS: Although physicians have become increasingly aware of overwhelming postsplenectomy infection in children, many remain unaware of the risk to asplenic or hyposplenic adults who may have no underlying medical problems. Recent studies have shown that many patients who have had splenectomies have had neither appropriate vaccinations nor teaching that would explain the lifelong nature of their risk. The increasing incidence of penicillin-resistant pneumococci represents a major area of therapeutic and prophylactic concern. The identification of Howell-Jolly bodies on a peripheral blood smear should alert physicians to the need for follow-up to document possible hyposplenism. Attention has focused on a three-pronged attack to this problem, including education, immunoprophylaxis, and chemoprophylaxis. CONCLUSIONS: Overwhelming postsplenectomy infection should be largely preventable if appropriate precautions are taken. Physicians need to know of the spectrum of diseases associated with hyposplenism and how patients noted to have Howell-Jolly bodies should be investigated. They should also be aware of appropriate guidelines for management of patients with asplenia or hyposplenism.

OBJECTIVE: Childhood obesity is associated with risk factors for cardiovascular disease. Arterial stiffness is considered one of the earliest detectable measures of vascular damage. There is controversy in the literature regarding the effects of childhood obesity on arterial stiffness. The objective of this study is to systematically review the literature and to conduct a meta-analysis comparing measures of central arterial stiffness in children and adolescents with obesity to healthy body mass index controls. APPROACH AND RESULTS: Literature searches were conducted using databases (eg, MEDLINE, EMBASE) and citations cross-referenced. Studies assessing central pulse wave velocity or β-stiffness index were included. A random effects meta-analysis of the standardized mean difference and 95% confidence intervals in arterial stiffness between children with obesity and control children was performed for each arterial stiffness measure. A total of 523 studies were identified. Fifteen case-control studies were included, with 2237 children/adolescents (1281 with obesity, 956 healthy body mass index controls) between 5 and 24 years of age. All studies measuring carotid and aortic β-stiffness index and 10/12 studies measuring central pulse wave velocity reported greater arterial stiffness in children/adolescents with obesity compared with controls. A random effects meta-analysis was performed revealing a significant effect of obesity on pulse wave velocity (standardized mean difference=0.718; 95% confidence interval=0.291-1.415), carotid β-stiffness index (0.862; 0.323-1.402), and aortic β stiffness index (1.017; 0.419-1.615). CONCLUSION: These findings indicate that child/adolescent obesity is associated with greater arterial stiffness. However, further research is needed to address confounders, such as pubertal status, that may affect this relationship in children. In the future, these techniques may be useful in risk stratification and guiding clinical management of obese children to optimize cardiovascular outcomes.

AIMS AND OBJECTIVES: To examine hospital nurses' attitudes towards caring for older adults and delineate associated factors contributing to their attitudes. BACKGROUND: Population ageing is of international significance. A nursing workforce able to care for the ageing population is critical for ensuring quality older adult care. A synthesis of research related to nurses' attitudes towards older adult care is important for informing care quality and the nursing workforce issues. METHODS: A systematic integrative review process guided the review. Cumulative Index of Nursing and Allied Health Literature and Medline databases were searched for primary research published between 2005-2017. A total of 1,690 papers were screened with 67 papers read in-depth and eight selected for this review that met the inclusion/exclusion criteria. RESULTS: Nurses' held coexisting positive and negative attitudes towards generic and specific aspects of older adult care. Negative attitudes, in particular, were directed at the characteristics of older adults, their care demands or reflected in nurses' approaches to care. Across jurisdictions, work environment, education, experience and demographics emerged as influences on nurses' attitudes. CONCLUSION: There is a paucity of research examining nurses' attitudes towards older adult care. The limited evidence indicates that attitudes towards older people care are complex and contradictory. Influences on nurses' attitudes need further study individually and collectively to build a strong evidence base. Interventional studies are needed as are the development of valid and reliable instruments for measuring nurses' attitudes towards older adult care. RELEVANCE TO CLINICAL PRACTICE: Bolstering postgraduate gerontological preparation is critical for promoting nurses' attitudes towards older adult care. Creating age-friendly work environments, including appropriate resource allocation, is important to support older people care and facilitate positive nursing attitudes.

OBJECTIVE: To determine if hearing loss, vision loss, and dual sensory loss were associated with social network diversity, social participation, availability of social support, and loneliness, respectively, in a population-based sample of older Canadians and to determine whether age or sex modified the associations. DESIGN: Cross-sectional population-based study. SETTING: Canada. PARTICIPANTS: The sample included 21 241 participants in the Canadian Longitudinal Study on Aging tracking cohort. The sample was nationally representative of English- and French-speaking, non-institutionalized 45- to 89-year-old Canadians who did not live on First Nations reserves and who had normal cognition. Participants with missing data for any of the variables in the multivariable regression models were excluded from analysis. MAIN OUTCOME MEASURES: was defined as reporting both hearing and vision loss. Univariate analyses were performed to assess cross-sectional associations between hearing, vision, and dual sensory loss, and social, demographic, and medical variables. Multivariable regression models were used to analyze cross-sectional associations between each type of sensory loss and social network diversity, social participation, availability of social support, and loneliness. RESULTS: Vision loss (in men) and dual sensory loss (in 65- to 85-year-olds) were independently associated with reduced social network diversity. Vision loss and dual sensory loss (in 65- to 85-year-olds) were each independently associated with reduced social participation. All forms of sensory loss were associated with both low availability of social support and loneliness. CONCLUSION: Sensory impairment is associated with reduced social function in older Canadians. Interventions and research that address the social needs of older individuals with sensory loss are needed.

Abstract Background: Access to integrated, palliative care regardless of location of residence is a palliative care standard yet we know such access is limited for those living in rural and remote settings. As a beginning step in the development of research aimed at informing policy and program development, a comprehensive review of the state of knowledge regarding palliative care in rural contexts is required. Purpose: To identify, evaluate and synthesize the published literature on rural palliative care. Design: Comprehensive review. Methods: Computer searches were conducted on PubBMed, ISI Web of Science, PsycInfo, CINAHL, and Ageline using the search terms palliative care, hospice, terminal care, end-of-life care, end-of-life, and rural or remote. Results: One hundred fifty-eight studies were retrieved. After screening using relevance and quality criteria, 79 studies were included in the review. Studies were grouped by subject matter into one of three categories: patient and caregiver perspectives; professional attitudes, knowledge and practice issues; and health care services. Conclusion: The body of research literature is small and eclectic, which means there is little strong evidence to inform palliative policy and service development in rural settings. Coordinated programs of research are clearly required to develop a body of knowledge that is adequate to support effective service and policy development.

ABSTRACT: The 2022 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Acute Stroke Management , 7 th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by an interdisciplinary team of healthcare providers and system planners caring for persons with an acute stroke or transient ischemic attack. These recommendations are a timely opportunity to reassess current processes to ensure efficient access to acute stroke diagnostics, treatments, and management strategies, proven to reduce mortality and morbidity. The topics covered include prehospital care, emergency department care, intravenous thrombolysis and endovascular thrombectomy (EVT), prevention and management of inhospital complications, vascular risk factor reduction, early rehabilitation, and end-of-life care. These recommendations pertain primarily to an acute ischemic vascular event. Notable changes in the 7 th edition include recommendations pertaining the use of tenecteplase, thrombolysis as a bridging therapy prior to mechanical thrombectomy, dual antiplatelet therapy for stroke prevention, 1 the management of symptomatic intracerebral hemorrhage following thrombolysis, acute stroke imaging, care of patients undergoing EVT, medical assistance in dying, and virtual stroke care. An explicit effort was made to address sex and gender differences wherever possible. The theme of the 7 th edition of the CSBPR is building connections to optimize individual outcomes, recognizing that many people who present with acute stroke often also have multiple comorbid conditions, are medically more complex, and require a coordinated interdisciplinary approach for optimal recovery. Additional materials to support timely implementation and quality monitoring of these recommendations are available at www.strokebestpractices.ca .

OBJECTIVE: It has been reported that Oppositional Defiant Disorder (ODD) can be differentiated into distinct subtypes associated with different outcomes in adulthood. We examined whether ODD is conceptually independent and coherent, and whether ODD and Conduct Disorder (CD) are expressions of the same core deficit. METHOD: The data come from a sample of 4,380 children for whom SNAP rating scales were available. Parallel analysis was performed on the eight-item ODD diagnostic items and on the SNAP-90 scale. These were factor analyzed and the components were correlated. RESULTS: ODD has one underlying factor, whereas the parent-rated SNAP has nine underlying factors. ODD items grouped together with emotional lability and irritability items, which did not group with CD. Confirmatory factor analysis supported the separation of ODD and CD but not ODD and emotion dysregulation. CONCLUSION: The expanded ODD factor more likely captures a disorder of emotion regulation, rather than a disruptive behavior disorder.

Endothelial function, assessed using brachial artery flow-mediated dilation (FMD), predicts future cardiovascular disease (CVD) risk. This study established age- and sex-specific reference intervals for brachial artery FMD in healthy individuals and examined the relation with CVD risk factors. In a retrospective study design, we pooled brachial artery FMD (acquired according to expert-consensus guidelines for FMD protocol and analysis) and participant characteristics/medical history from 5362 individuals (4–84 years; 2076 females). Healthy individuals (n=1403 [582 females]) were used to generate age-/sex-specific percentile curves. Subsequently, we included individuals with CVD risk factors, without overt disease (unmedicated n=3167 [1247 females] and medicated n=792 [247 females]). Multiple linear regression tested the relation of CVD risk factors (body mass index, blood pressure, cholesterol, diabetes, dyslipidemia, and smoking) with FMD. Healthy males showed a negative, curvilinear relation between FMD and age, while females revealed a negative linear relation that started higher but declined at a faster rate than males. Age- and sex-specific differences in FMD relate, at least partly, to baseline artery diameter. FMD was related to CVD risk factors in unmedicated (eg, systolic/diastolic blood pressure) and medicated individuals (eg, diabetes/dyslipidemia). Sex mediated some of these effects ( P <0.05), with normalization of FMD in medicated men, but not women with dyslipidemia. In conclusion, sex alters the age-related decline in FMD, which may partly be explained through differences in baseline diameter. Sex also alters the influence of some CVD risk factors and medication on FMD. This work improves interpretation and future use of the FMD technique.

BACKGROUND: Patients with T-cell lymphomas face a poorer prognosis compared with patients with B-cell lymphomas. New therapeutic approaches need to be developed to improve outcomes for these patients. METHODS: Forty patients with recurrent and refractory T-cell lymphomas other than mycosis fungoides and patients with untreated T-cell lymphoma who were not candidates for combination chemotherapy were prescribed oral lenalidomide at a dose of 25 mg daily on days 1 to 21 of each 28-day cycle, with standardized dose reductions for toxicity. The primary endpoint was overall response rate (ORR), and secondary endpoints were complete and partial response rates, progression-free survival (PFS), overall survival (OS), and safety. The authors also determined duration of response (DoR). RESULTS: A total of 40 patients were enrolled in the current study; 1 patient was subsequently deemed ineligible. The ORR was 10 of 39 patients (26%); 3 patients (8%) achieved complete responses and 7 patients achieved partial responses. Three patients had stable disease for ≥5 cycles. The median OS was 12 months (range <1 month to ≥69 months), the median PFS was 4 months (range, <1 month to ≥50 months), and the median DoR was 13 months (range 2 months to ≥37 months), including 5 responses that lasted >1 year. Toxicity was in keeping with the known safety profile of lenalidomide. Among the patients who had recurrent/refractory peripheral T-cell lymphoma (29 patients), the ORR was 24%, the median OS was 12 months, the median PFS was 4 months, and the median DoR was 5 months (range, 2 months to ≥37 months). CONCLUSIONS: In the current study, the use of oral lenalidomide monotherapy demonstrated clinically relevant efficacy among patients with systemic T-cell lymphomas. It appears to have excellent potential as an agent in combination therapy for patients with T-cell lymphoma.

BACKGROUND: Key performance indicators (KPIs) are quantifiable measures of quality. There are no published, systematically derived clinical pharmacy KPIs (cpKPIs). OBJECTIVE: A group of hospital pharmacists aimed to develop national cpKPIs to advance clinical pharmacy practice and improve patient care. METHODS: A cpKPI working group established a cpKPI definition, 8 evidence-derived cpKPI critical activity areas, 26 candidate cpKPIs, and 11 cpKPI ideal attributes in addition to 1 overall consensus criterion. Twenty-six clinical pharmacists and hospital pharmacy leaders participated in an internet-based 3-round modified Delphi survey. Panelists rated 26 candidate cpKPIs using 11 cpKPI ideal attributes and 1 overall consensus criterion on a 9-point Likert scale. A meeting was facilitated between rounds 2 and 3 to debate the merits and wording of candidate cpKPIs. Consensus was reached if 75% or more of panelists assigned a score of 7 to 9 on the consensus criterion during the third Delphi round. RESULTS: All panelists completed the 3 Delphi rounds, and 25/26 (96%) attended the meeting. Eight candidate cpKPIs met the consensus definition: (1) performing admission medication reconciliation (including best-possible medication history), (2) participating in interprofessional patient care rounds, (3) completing pharmaceutical care plans, (4) resolving drug therapy problems, (5) providing in-person disease and medication education to patients, (6) providing discharge patient medication education, (7) performing discharge medication reconciliation, and (8) providing bundled, proactive direct patient care activities. CONCLUSIONS: A Delphi panel of hospital pharmacists was successful in determining 8 consensus cpKPIs. Measurement and assessment of these cpKPIs will serve to advance clinical pharmacy practice and improve patient care.

OBJECTIVE: To determine whether physical exercise constitutes a benefit or a risk in the development and progression of knee osteoarthritis. QUALITY OF EVIDENCE: MEDLINE, EMBASE, DARE, ACP Journal Club, and Cochrane databases were searched from registry inception to January 2009 using MeSH headings or text words, including osteoarthritis, arthritis and knee and exercise, physical training, and run. Reference lists from retrieved articles, citation listings when available, and related articles suggested in PubMed were also evaluated. For individuals without osteoarthritis, strong level II evidence was found (limited by problems with blinding and randomization); for those with pre-existing knee osteoarthritis, robust level I evidence was available. MAIN MESSAGE: Knee osteoarthritis is a major contributor to disability in seniors, and patients have expressed concern that continued exercise might lead to knee symptoms in later years. Studies done on subjects self-selected for exercise and followed for substantial periods of time show no evidence of accelerated development of osteoarthritis, provided injury is avoided. Further, there is good evidence for reduced pain and disability with exercise in this cohort compared with controls. Patients with established osteoarthritis are shown to derive uniform benefit to physical functioning, with reduction of pain and disability, using aerobic, muscle strengthening, aquatic, or physiotherapy-based exercise modalities. CONCLUSION: Provided trauma is avoided, moderate exercise does not lead to acceleration of knee osteoarthritis, whether or not there is evidence of pre-existing disease. In either case there appears to be improved physical functioning and reduction of pain and disability in those who exercise. It is likely that exercise interventions are underused in the management of established knee osteoarthritis symptoms.

NEW FINDINGS: What is the topic of this review? This review provides an up-to-date assessment of the physiology involved with extreme static dry-land breath holding in trained apneists. What advances does it highlight? We specifically highlight the recent findings involved with the cardiovascular, cerebrovascular and metabolic function during a maximal breath hold in elite apneists. ABSTRACT: Breath-hold-related activities have been performed for centuries, but only recently, within the last ∼30 years, has it emerged as an increasingly popular competitive sport. In apnoea sport, competition relates to underwater distances or simply maximal breath-hold duration, with the current (oxygen-unsupplemented) static breath-hold record at 11 min 35 s. Remarkably, many ultra-elite apneists are able to suppress respiratory urges to the point where consciousness fundamentally limits a breath-hold duration. Here, arterial oxygen saturations as low as ∼50% have been reported. In such cases, oxygen conservation to maintain cerebral functioning is critical, where responses ascribed to the mammalian dive reflex, e.g. sympathetically mediated peripheral vasoconstriction and vagally mediated bradycardia, are central. In defence of maintaining global cerebral oxygen delivery during prolonged breath holds, the cerebral blood flow may increase by ∼100% from resting values. Interestingly, near the termination of prolonged dry static breath holds, recent studies also indicate that reductions in the cerebral oxidative metabolism can occur, probably attributable to the extreme hypercapnia and irrespective of the hypoxaemia. In this review, we highlight and discuss the recent data on the cardiovascular, metabolic and, particularly, cerebrovascular function in competitive apneists performing maximal static breath holds. The physiological adaptation and maladaptation with regular breath-hold training are also summarized, and future research areas in this unique physiological field are highlighted; particularly, the need to determine the potential long-term health impacts of extreme breath holding.

A previous study showed that measurements of total-body bone mineral changes made with a Hologic QDR 1000W were unreliable when the subjects underwent weight change. The study has been extended to dual energy X-ray absorptiometry (DXA) apparatus from other manufacturers. Re-analysis of published results during weight loss using a Lunar DPX showed that they varied with the software used. Using the Extended mode, there was a 1% loss of bone mineral areal density (BMD), but no significant change in bone mineral content (BMC) or bone area (BA) following a weight loss of 16 kg, whereas the use of the Standard mode led to a larger fall of BMC and BMD. Similar findings arose from the consideration of two studies using Norland XR 26 HS absorptiometers. On the other hand, separation of two groups with similar weight changes from the population studied with a Hologic QDR 1000W confirmed that BMC changed directly with weight, but there was an inverse relationship for BMD, owing to an inappropriate change of BA. The use of Hologic Enhanced and Standard software modes led to significant differences in initial readings and measured changes. With each instrument there was a strong correlation between changes in BA and changes in BMC. When 6 kg of lard was wrapped around the limbs of volunteers or a semi-anthropomorphic phantom to simulate weight change, there were spurious increases of measured BMC and BA by about 5% with each instrument. There were no changes of BMD with Lunar, variable results with Norland, but decreases with Hologic. The results observed in vivo could be explained by the effects of fat changes, without there being any real change of bone mineral. Changes of BMD in the skeleton of the phantom were underestimated with all three brands. The anomaly observed with the Hologic QDR 1000W is less apparent with a Lunar DPX or a Norland XR 26, but there are sufficient uncertainties for all total-body measurements during weight change to be treated with suspicion.