Low- and high-volume blood-flow restriction treadmill walking both improve maximal aerobic capacity independently of blood volume.

AIM: Assess the effect of low- and high-volume blood flow restriction training (BFR) on maximal aerobic capacity (VO2 max) and determine if alteration in VO2 max is mediated through changes in hemoglobin mass (Hbmass) and blood volume. METHODS: Participants' Hbmass (CO-rebreathe), single, and double-leg VO2 max and blood volume regulating hormonal responses (renin and copeptin) were measured before and after BFR training. Training consisted of treadmill walking either (1) twice-daily for 4week (CON and BFRHV ) or (2) twice-weekly for 6week (BFRLV ). Each session consisted of five intervals (3 min, 5% incline, 5 km/h, 100% of lowest occlusion pressure), with 1 min of standing rest between sets. RESULTS: VO2 max increased using both training exposures, in as quickly as 2-weeks (BFRLV baseline to 4week: +315 ± 241 mL (8.7%), p = 0.02; BFRHV baseline to 2week: +360 ± 261 mL (7.9%), p < 0.01), for the BFRLV and BFRHV groups, with no change in CON. Single- and double-leg VO2 max improved proportionately (single/double-leg VO2 max ratio: BFRLV 78 ± 4.9-78 ± 5.8%, BFRHV 79 ± 6.5-77 ± 6.5%), suggesting that the mechanism for increased VO2 max is not solely limited to central or peripheral adaptations. Hbmass remained unchanged across groups (CON: +10.2 ± 34 g, BFRLV : +6.6 ± 42 g, BFRHV : +3.2 ± 44 g; p = 0.9), despite a significant release of blood volume regulating hormones after initial BFR exposure (renin +20.8 ± 21.9 ng/L, p < 0.01; copeptin +22.0 ± 23.8 pmol/L, p < 0.01), which was blunted following BFRHV training (renin: +13.4 ± 12.4 ng/L, p = 0.09; copeptin: +1.9 ± 1.7 pmol/L, p = 0.98). CONCLUSION: BFR treadmill walking increases VO2 max irrespective of changes in Hbmass or blood volume despite a large release of blood volume regulating hormones in response to BFR treadmill walking.

Physical Frailty and Cognitive Function among Older Chinese Adults: The Mediating Roles of Activities of Daily Living Limitations and Depression.

BACKGROUND: Physical frailty and cognitive impairment are prevalent globally, particularly in China, which is experiencing an unprecedented aging of its large population. OBJECTIVES: Examine the association between physical frailty and the level and rate of change of cognitive function, globally and by domain, among community-dwelling Chinese older adults, and quantify the mediation effects from activities of daily living (ADL) limitations and depressive symptoms. DESIGN: Longitudinal. SETTING: China Health and Retirement Longitudinal Study (2011-2018). PARTICIPANTS: 5,431 eligible adults aged ≥ 60 years with valid information on physical frailty. MEASUREMENTS: Physical frailty, cognitive function, ADL limitations, and depressive symptoms were respectively assessed by frailty phenotypes, the Telephone Interview for Cognitive Status (episodic memory, executive function, and orientation), performance in six daily tasks, and the eight-item Center for Epidemiological Studies Depression Scale. Latent growth curve models were used to address the objectives. RESULTS: Compared to adults who were non-frail, those who were pre-frail (ß = -0.06) and frail (ß = -0.13) reported significantly worse global cognitive function and episodic memory (pre-frail: ß = -0.05; frail: ß = -0.14), executive function (pre-frail: ß = -0.04, frail: ß = -0.10), and orientation (pre-frail: ß = -0.06; frail: ß = -0.07) at baseline; those who were frail were more likely to experience faster decline in global cognitive function (ß = 0.12) and episodic memory (ß = 0.08). ADL limitations (ß = -0.07) and depressive symptoms (ß = -0.14) significantly mediated the association between physical frailty and the level of cognitive function, but not its rate of decline. CONCLUSIONS: Intervention strategies that help maintain cognitive function may benefit from early screening and assessment of physical frailty. For pre-frail and frail older Chinese adults, programs designed to help improve or maintain activities of daily living and reduce number of depressive symptoms may contribute to better cognitive performance.

Training response to 8 weeks of blood flow restricted training is not improved by preferentially altering tissue hypoxia or lactate accumulation when training to repetition failure.

Despite compelling muscular structure and function changes resulting from blood flow restricted (BFR) resistance training, mechanisms of action remain poorly characterized. Alterations in tissue O2 saturation (TSI%) and metabolites are potential drivers of observed changes, but their relationships with degree of occlusion pressure are unclear. We examined local TSI% and blood lactate (BL) concentration during BFR training to failure using different occlusion pressures on strength, hypertrophy, and muscular endurance over an 8-week training period. Twenty participants (11 males/9 females) trained 3/wk for 8 wk using high pressure (100% resting limb occlusion pressure, LOP; 20% one-repetition maximum (1RM)), moderate pressure (50% LOP, 20%1RM), or traditional resistance training (TRT; 70%1RM). Strength, size, and muscular endurance were measured pre/post training. TSI% and BL were quantified during a training session. Despite overall increases, no group preferentially increased strength, hypertrophy, or muscular endurance (p > 0.05). Neither TSI% nor BL concentration differed between groups (p > 0.05). Moderate pressure resulted in greater accumulated deoxygenation stress (TSI% × time) (-6352 ± 3081, -3939 ± 1835, -2532 ± 1349 au for moderate pressure, high pressure, and TRT, p = 0.018). We demonstrate that BFR training to task-failure elicits similar strength, hypertrophy, and muscular endurance changes to TRT. Further, varied occlusion pressure does not impact these outcomes or elicit changes in TSI% or BL concentrations. Novelty: Training to task failure with low-load blood flow restriction elicits similar improvements to traditional resistance training, regardless of occlusion pressure. During blood flow restriction, altering occlusion pressure does not proportionally impact tissue O2 saturation nor blood lactate concentrations.

An examination of individual responses to ischemic preconditioning and the effect of repeated ischemic preconditioning on cycling performance.

PURPOSE: To use repeated control trials to measure within-subject variability and assess the existence of responders to ischemic preconditioning (IPC). Secondly, to determine whether repeated IPC can evoke a dosed ergogenic response. METHODS: Twelve aerobically fit individuals each completed three control and three IPC 5-km cycling time trials. IPC trials included: (i) IPC 15-min preceding the trial (traditional IPC), (ii) IPC 24-h and 15-min preceding (IPC × 2), (iii) IPC 48-h, 24-h, and 15-min preceding (IPC × 3). IPC consisted of 3 × 5-min cycles of occlusion and reperfusion at the upper thighs. To assess the existence of a true response to IPC, individual performance following traditional IPC was compared to each individual's own 5-km TT coefficient of variation. In individuals who responded to IPC, all three IPC conditions were compared to the mean of the three control trials (CONavg) to determine whether repeated IPC can evoke a dosed ergogenic response. RESULTS: 9 of 12 (75%) participants improved 5-km time (-1.8 ± 1.7%) following traditional IPC, however, only 7 of 12 (58%) improved greater than their own variability between repeated controls (true responders). In true responders only, we observed a significant mean improvement in 5-km TT completion following traditional IPC (478 ± 50 s), IPC × 2 (481 ± 51 s), and IPC × 3 (480.5 ± 49 s) compared to mean CONavg (488 ± 51s; p < 0.006), with no differences between various IPC trials (p > 0.05). CONCLUSION: A majority of participants responded to IPC, providing support for a meaningful IPC-mediated performance benefit. However, repeated bouts of IPC on consecutive days do not enhance the ergogenic effect of a single bout of IPC.

Barriers to and enablers of diabetic retinopathy screening attendance: a systematic review of published and grey literature.

AIMS: To identify and synthesize studies reporting modifiable barriers/enablers associated with retinopathy screening attendance in people with Type 1 or Type 2 diabetes, and to identify those most likely to influence attendance. METHODS: We searched MEDLINE, EMBASE, PsycINFO, Cochrane Library and the 'grey literature' for quantitative and qualitative studies to February 2017. Data (i.e. participant quotations, interpretive summaries, survey results) reporting barriers/enablers were extracted and deductively coded into domains from the Theoretical Domains Framework; with domains representing categories of theoretical barriers/enablers proposed to mediate behaviour change. Inductive thematic analysis was conducted within domains to describe the role each domain plays in facilitating or hindering screening attendance. Domains that were more frequently coded and for which more themes were generated were judged more likely to influence attendance. RESULTS: Sixty-nine primary studies were included. We identified six theoretical domains ['environmental context and resources' (75% of included studies), 'social influences' (51%), 'knowledge' (51%), 'memory, attention, decision processes' (50%), 'beliefs about consequences' (38%) and 'emotions' (33%)] as the key mediators of diabetic retinopathy screening attendance. Examples of barriers populating these domains included inaccurate diabetic registers and confusion between routine eye care and retinopathy screening. Recommendations by healthcare professionals and community-level media coverage acted as enablers. CONCLUSIONS: Across a variety of contexts, we found common barriers to and enablers of retinopathy screening that could be targeted in interventions aiming to increase screening attendance.

An evaluation of the relative safety of U.S. mining explosion-protected equipment approval requirements versus international standards.

This paper provides a determination of the equivalent level of protection of the international standards relative to similar criteria used by the U.S. Mine Safety and Health Administration (MSHA) to approve two-fault intrinsically safe (IS) stand-alone equipment. U.S. mining law requires such a determination for MSHA to use alternatives to existing standards. The primary issue is to demonstrate that the international standards for equipment evaluation will provide at least the same level of protection for miners as the document currently used by MSHA.

Monitoring ocular hypertension, how much and how often? A cost-effectiveness perspective.

OBJECTIVE: To assess the efficiency of alternative monitoring services for people with ocular hypertension (OHT), a glaucoma risk factor. DESIGN: Discrete event simulation model comparing five alternative care pathways: treatment at OHT diagnosis with minimal monitoring; biennial monitoring (primary and secondary care) with treatment if baseline predicted 5-year glaucoma risk is ≥6%; monitoring and treatment aligned to National Institute for Health and Care Excellence (NICE) glaucoma guidance (conservative and intensive). SETTING: UK health services perspective. PARTICIPANTS: Simulated cohort of 10 000 adults with OHT (mean intraocular pressure (IOP) 24.9 mm Hg (SD 2.4). MAIN OUTCOME MEASURES: Costs, glaucoma detected, quality-adjusted life years (QALYs). RESULTS: Treating at diagnosis was the least costly and least effective in avoiding glaucoma and progression. Intensive monitoring following NICE guidance was the most costly and effective. However, considering a wider cost-utility perspective, biennial monitoring was less costly and provided more QALYs than NICE pathways, but was unlikely to be cost-effective compared with treating at diagnosis (£86 717 per additional QALY gained). The findings were robust to risk thresholds for initiating monitoring but were sensitive to treatment threshold, National Health Service costs and treatment adherence. CONCLUSIONS: For confirmed OHT, glaucoma monitoring more frequently than every 2 years is unlikely to be efficient. Primary treatment and minimal monitoring (assessing treatment responsiveness (IOP)) could be considered; however, further data to refine glaucoma risk prediction models and value patient preferences for treatment are needed. Consideration to innovative and affordable service redesign focused on treatment responsiveness rather than more glaucoma testing is recommended.

Arterial stiffness results from eccentrically biased downhill running exercise.

OBJECTIVES: There is increasing evidence that select forms of exercise are associated with vascular changes that are in opposition to the well-accepted beneficial effects of moderate intensity aerobic exercise. To determine if alterations in arterial stiffness occur following eccentrically accentuated aerobic exercise, and if changes are associated with measures of muscle soreness. DESIGN: Repeated measures experimental cohort. METHODS: Twelve (m=8/f=4) moderately trained (VO2max=52.2 ± 7.4 ml kg(-1)min(-1)) participants performed a downhill run at -12° grade using a speed that elicited 60% VO2max for 40 min. Cardiovascular and muscle soreness measures were collected at baseline and up to 72 h post-running. RESULTS: Muscle soreness peaked at 48 h (p=<0.001). Arterial stiffness similarly peaked at 48 h (p=0.04) and remained significantly elevated above baseline through 72 h. CONCLUSIONS: Eccentrically accentuated downhill running is associated with arterial stiffening in the absence of an extremely prolonged duration or fast pace. The timing of alterations coincides with the well-documented inflammatory response that occurs from the muscular insult of downhill running, but whether the observed changes are a result of either systemic or local inflammation is yet unclear. These findings may help to explain evidence of arterial stiffening in long-term runners and following prolonged duration races wherein cumulative eccentric loading is high.

Cost-effectiveness of ultrasound-guided foam sclerotherapy, endovenous laser ablation or surgery as treatment for primary varicose veins from the randomized CLASS trial.

BACKGROUND: The treatment of patients with varicose veins constitutes a considerable workload and financial burden to the National Health Service. This study aimed to assess the cost-effectiveness of ultrasound-guided foam sclerotherapy (UGFS) and endovenous laser ablation (EVLA) compared with conventional surgery as treatment for primary varicose veins. METHODS: Participant cost and utility data were collected alongside the UK CLASS multicentre randomized clinical trial, which compared EVLA, surgery and UGFS. Regression methods were used to estimate the effects of the alternative treatments on costs to the health service and quality-adjusted life-years (QALYs) at 6 months. A Markov model, incorporating available evidence on clinical recurrence rates, was developed to extrapolate the trial data over a 5-year time horizon. RESULTS: Compared with surgery at 6 months, UGFS and EVLA reduced mean costs to the health service by £655 and £160 respectively. When additional overhead costs associated with theatre use were included, these cost savings increased to £902 and £392 respectively. UGFS produced 0·005 fewer QALYs, whereas EVLA produced 0·011 additional QALYs. Extrapolating to 5 years, EVLA was associated with increased costs and QALYs compared with UGFS (costing £3640 per QALY gained), and generated a cost saving (£206-439) and QALY gain (0·078) compared with surgery. Applying a ceiling willingness-to-pay ratio of £20 000 per QALY gained, EVLA had the highest probability (78·7 per cent) of being cost-effective. CONCLUSION: The results suggest, for patients considered eligible for all three treatment options, that EVLA has the highest probability of being cost-effective at accepted thresholds of willingness to pay per QALY.

Optical coherence tomography for the diagnosis of neovascular age-related macular degeneration: a systematic review.

UNLABELLED: The purpose is to study the diagnostic performance of optical coherence tomography (OCT) and alternative diagnostic tests for neovascular age-related macular degeneration (nAMD). Methods employed are as follows:systematic review and meta-analysis; INDEX TEST: OCT including time-domain (TD-OCT) and the most recently developed spectral domain (SD-OCT); comparator tests: visual acuity, clinical evaluation (slit lamp), Amsler chart, colour fundus photographs, infra-red reflectance, red-free images/blue reflectance, fundus autofluorescence imaging (FAF), indocyanine green angiography (ICGA), preferential hyperacuity perimetry (PHP), and microperimetry; reference standard: fundus fluorescein angiography. Databases searched included MEDLINE, MEDLINE In Process, EMBASE, Biosis, SCI, the Cochrane Library, DARE, MEDION, and HTA database. Last literature searches: March 2013. Risk of bias assessed using QUADAS-2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic (HSROC) curves. Twenty-two studies (2 abstracts and 20 articles) enrolling 2124 participants were identified, reporting TD-OCT (12 studies), SD-OCT (1 study), ICGA (8 studies), PHP (3 studies), Amsler grid, colour fundus photography and FAF (1 study each). Most studies were considered to have a high risk of bias in the patient selection (55%, 11/20), and flow and timing (40%, 8/20) domains. In a meta-analysis of TD-OCT studies, sensitivity and specificity (95% CI) were 88% (46-98%) and 78% (64-88%), respectively. There was insufficient information to undertake meta-analysis for other tests. TD-OCT is a sensitive test for detecting nAMD, although specificity was only moderate. Data on SD-OCT are sparse. Diagnosis of nAMD should not rely solely on OCT.

An introduction to patient-reported outcome measures in ophthalmic research.

Clinical outcomes, such as quantifying the extent of visual field loss by automated perimetry, are valued highly by health professionals, but such measures do not capture the impact of the condition on a patient's life. Patient-reported outcomes describe any report or measure of health reported by the patient, without external interpretation by a clinician or researcher. In this review, we discuss the value of the measures that capture this information (patient-reported outcome measures; PROMs), and why they are important to both the clinician and the researcher. We also consider issues around developing or selecting a PROM for ophthalmic research, the emerging challenges around conducting and reporting PROMs in clinical trials and highlight best practice for their use. Search terms for this review comprised: (1) (patient-reported outcomes OR patient-reported outcome measures) AND (2) randomised controlled trials AND (3) limited to ophthalmic conditions. These terms were expanded as follows: ((('patients'(MeSH Terms) OR 'patients'(All Fields) OR 'patient'(All Fields)) AND ('research report'(MeSH Terms) OR ('research'(All Fields) AND 'report'(All Fields)) OR 'research report'(All Fields) OR 'reported'(All Fields)) AND outcomes(All Fields)) OR (('patients'(MeSH Terms) OR 'patients'(All Fields) OR 'patient'(All Fields)) AND ('research report'(MeSH Terms) OR ('research'(All Fields) AND 'report'(All Fields)) OR 'research report'(All Fields) OR 'reported'(All Fields) AND ('outcome assessment (health care)'(MeSH Terms) OR ('outcome'(All Fields) AND 'assessment'(All Fields) AND '(health'(All Fields) AND 'care)'(All Fields)) OR 'outcome assessment (health care)'(All Fields) OR ('outcome'(All Fields) AND 'measures'(All Fields)) OR 'outcome measures'(All Fields)))) AND ('randomized controlled trial'(Publication Type) OR 'randomized controlled trials as topic'(MeSH Terms) OR 'randomised controlled trials'(All Fields) OR 'randomized controlled trials'(All Fields)) AND (ophth*(All Fields)). The authors also utilised the extensive non-ophthalmic literature and online resources relating to PROs and PROMs to inform this review.

Validation of a short questionnaire for estimating dietary calcium intakes.

UNLABELLED: Concern about calcium supplements, and mainly minor side effects (e.g. constipation) impacting on compliance, means that assessing dietary calcium intake is important. There is no suitable biomarker. Compared to food diaries, a short questionnaire was an efficient way of confirming that patients had adequate calcium intakes (>700 or >1,000 mg) INTRODUCTION: Calcium is usually given alongside treatments for osteoporosis, but recent concerns about potential side effects have led to questioning whether supplements are always necessary. It is difficult to assess calcium intake in a clinical setting and be certain that the patient is getting enough calcium. The aim of this study was to determine whether a short questionnaire for estimating dietary calcium intakes in a clinical setting was fit for purpose. METHODS: We assessed dietary calcium intakes using a short questionnaire (CaQ) in patients attending an osteoporosis clinic (n = 117) and compared them with calcium intakes obtained from a 7-day food diary (n = 72) and a food frequency questionnaire (FFQ) (n = 33). RESULTS: Mean (SD) daily calcium intakes from the CaQ were 836 (348) mg; from the diaries, 949 (384) mg; and from the FFQ, 1,141 (387) mg. The positive predictive value (PPV) was >80% for calcium cut-offs > 700 mg and 70% for cut-offs > 1,000 mg. The calcium intakes for the false positives results were not far below the cut-off. For 1,200 mg, the PPV was 67% or less. CONCLUSION: The CaQ is an adequate tool for assessing whether a patient has daily calcium intakes above 700 or 1,000 mg; if below these cut-offs, it is possible that the patient still has enough calcium in the diet, which could be clarified by questioning the patient further. As there were few patients with calcium intakes above 1,200 mg a day, the CaQ cannot be recommended as a tool for confirming higher dietary calcium intakes.

Temporal response of arterial stiffness to ultra-marathon.

The purpose of this investigation was to characterize the arterial stiffness of male ultra-marathon runners (n = 9) using pulse wave velocity (cfPWV) and radial tonometry over the course of an ultra-marathon and during recovery. Measures were collected at rest, immediately following 45 km/75 km of running, then following 60 and 90 min of recovery. No statistical difference was found between baseline cfPWV and normative values. The cfPWV of ultra-endurance runners decreased at 45 km (3.4 ± 1.6 m/s, p=0.006), followed by an increase (1.6 ± 1.8 m/s, p = 0.04) toward baseline levels at the 75 km mark. Radial tonometry measures also indicated small artery stiffness was transiently increased after 75 km. The amount of training time (r = 0.82, p = 0.007) and the duration of a typical training session (r = 0.73, p = 0.03) were correlated strongly with persisting decrements in large artery compliance at 60 min of recovery. The finding that arterial stiffness decreased at the 45 km distance and then reverted back toward baseline levels with prolonged running, may indicate a role of exercise duration or accumulated stress for affecting vascular compliance. At present, it is premature to suggest that athletes should alter training or racing practices to protect vascular health.

Types of urethral catheter for reducing symptomatic urinary tract infections in hospitalised adults requiring short-term catheterisation: multicentre randomised controlled trial and economic evaluation of antimicrobial- and antiseptic-impregnated urethral catheters (the CATHETER trial).

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is a major preventable cause of harm for patients in hospital and incurs significant costs for health-care providers such as the UK NHS. Many preventative strategies and measures have been introduced to minimise CAUTI risk, including the use of antimicrobial catheters. However, there is considerable uncertainty regarding their usefulness in terms of reducing symptomatic CAUTI, and whether or not they are cost-effective. OBJECTIVES: Do antimicrobial catheters reduce the rate of symptomatic urinary tract infection (UTI) during short-term hospital use and is their use cost-effective for the UK NHS? DESIGN: A pragmatic multicentre UK randomised controlled trial comparing three catheters as they would be used in the UK NHS: antimicrobial-impregnated (nitrofurazone) and antiseptic-coated (silver alloy) catheters with the standard polytetrafluoroethylene (PTFE)-coated catheters. Economic evaluation used a decision model populated with data from the trial. Sensitivity analysis was used to explore uncertainty. SETTING: Relevant clinical departments in 24 NHS hospitals throughout the UK. PARTICIPANTS: Adults requiring temporary urethral catheterisation for a period of between 1 and 14 days as part of their care, predominantly as a result of elective surgery. INTERVENTIONS: Eligible participants were randomised 1 : 1 : 1 to one of three types of urethral catheter in order to make the following pragmatic comparisons: nitrofurazone-impregnated silicone catheter compared with standard PTFE-coated latex catheter; and silver alloy-coated hydrogel latex catheter compared with standard PTFE-coated latex catheter. MAIN OUTCOME MEASURES: The primary outcome for clinical effectiveness was the incidence of UTI at any time up to 6 weeks post randomisation. This was defined as any symptom reported during catheterisation, up to 3 days or 1 or 2 weeks post catheter removal or 6 weeks post randomisation combined with a prescription of antibiotics, at any of these times, for presumed symptomatic UTI. The primary economic outcome was incremental cost per quality-adjusted life-year (QALY). Health-care costs were estimated from NHS sources with QALYs calculated from participant completion of the European Quality of Life-5 Dimensions (EQ-5D). RESULTS: Outcome analyses encompassed 6394 (90%) of 7102 participants randomised. The rate of symptomatic UTI within 6 weeks of randomisation was 10.6% in the nitrofurazone group (n = 2153; -2.1% absolute risk difference), 12.5% in the silver alloy group (n = 2097; -0.1% absolute risk difference) and 12.6% in the PTFE group (n = 2144). The effect size {odds ratio (OR) [97.5% confidence interval (CI)]} was 0.82 (97.5% CI 0.66 to 1.01) for nitrofurazone (p = 0.037) and 0.99 (97.5% CI 0.81 to 1.22) for silver alloy (p = 0.92) catheters. The nitrofurazone catheters were more likely to cause discomfort during use and on removal. The primary economic analysis suggested that nitrofurazone-impregnated catheters would be, on average, the least costly (> £7 less than PTFE) and most effective option at current NHS prices. There was a 73% chance that nitrofurazone would be cost saving and an 84% chance that the incremental cost per QALY would be < £30,000. At the trial price (£6.46), silver alloy catheters were very unlikely to be cost-effective. These results were unchanged in sensitivity analyses, although when the length of stay cost was excluded the incremental cost per QALY for nitrofurazone against PTFE was £28,602. CONCLUSIONS: The trial estimate of clinical effectiveness for nitrofurazone-impregnated catheters was less than the pre-specified minimum absolute risk difference that we considered important (-3.3%), and the surrounding CI included zero, indicating that any reduction in catheter-associated UTI was uncertain. Economic analysis, although associated with uncertainty, suggested that nitrofurazone-impregnated catheters may be cost-effective for the NHS. The trial ruled out the possibility that silver alloy-coated catheters might reach the pre-set degree of clinical effectiveness and that their use was unlikely to be cost-effective. These findings should be considered by patients, clinicians and health-care policy-makers to determine whether or not a change in practice is worthwhile. Future research should be aimed at determining the minimum clinically important difference in terms of CAUTI prevention in comparative trials, and to identify reliable methods which can detect the impact of the intervention on quality of life and other drivers of cost, when the intervention is a subsidiary part of overall treatment plans.

Surveillance for ocular hypertension: an evidence synthesis and economic evaluation.

OBJECTIVES: To determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of glaucoma risk prediction models; and (ii) development of models to determine optimal surveillance pathways. DESIGN: A discrete event simulation economic modelling evaluation. Data from systematic reviews of risk prediction models and agreement between tonometers, secondary analyses of existing datasets (to validate identified risk models and determine optimal monitoring criteria) and public preferences were used to structure and populate the economic model. SETTING: Primary and secondary care. PARTICIPANTS: Adults with ocular hypertension (IOP > 21 mmHg) and the public (surveillance preferences). INTERVENTIONS: We compared five pathways: two based on National Institute for Health and Clinical Excellence (NICE) guidelines with monitoring interval and treatment depending on initial risk stratification, 'NICE intensive' (4-monthly to annual monitoring) and 'NICE conservative' (6-monthly to biennial monitoring); two pathways, differing in location (hospital and community), with monitoring biennially and treatment initiated for a ≥ 6% 5-year glaucoma risk; and a 'treat all' pathway involving treatment with a prostaglandin analogue if IOP > 21 mmHg and IOP measured annually in the community. MAIN OUTCOME MEASURES: Glaucoma cases detected; tonometer agreement; public preferences; costs; willingness to pay and quality-adjusted life-years (QALYs). RESULTS: The best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors (IOP, central corneal thickness, optic nerve damage and index of visual field status). Taking the average of two IOP readings, by tonometry, true change was detected at two years. Sizeable measurement variability was noted between tonometers. There was a general public preference for monitoring; good communication and understanding of the process predicted service value. 'Treat all' was the least costly and 'NICE intensive' the most costly pathway. Biennial monitoring reduced the number of cases of glaucoma conversion compared with a 'treat all' pathway and provided more QALYs, but the incremental cost-effectiveness ratio (ICER) was considerably more than £30,000. The 'NICE intensive' pathway also avoided glaucoma conversion, but NICE-based pathways were either dominated (more costly and less effective) by biennial hospital monitoring or had a ICERs > £30,000. Results were not sensitive to the risk threshold for initiating surveillance but were sensitive to the risk threshold for initiating treatment, NHS costs and treatment adherence. LIMITATIONS: Optimal monitoring intervals were based on IOP data. There were insufficient data to determine the optimal frequency of measurement of the visual field or optic nerve head for identification of glaucoma. The economic modelling took a 20-year time horizon which may be insufficient to capture long-term benefits. Sensitivity analyses may not fully capture the uncertainty surrounding parameter estimates. CONCLUSIONS: For confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring. Consideration of the patient experience is important. A cohort study is recommended to provide data to refine the glaucoma risk prediction model, determine the optimum type and frequency of serial glaucoma tests and estimate costs and patient preferences for monitoring and treatment. FUNDING: The National Institute for Health Research Health Technology Assessment Programme.

Systemic arterial compliance following ultra-marathon.

There is a growing interest in training for and competing in race distances that exceed the marathon; however, little is known regarding the vascular effects of participation in such prolonged events, which last multiple consecutive hours. There exists some evidence that cardiovascular function may be impaired following extreme prolonged exercise, but at present, only cardiac function has been specifically examined following exposure to this nature of exercise. The primary purpose of this study was to characterize the acute effects of participation in an ultra-marathon on resting systemic arterial compliance. Arterial compliance and various resting cardiovascular indices were collected at rest from 26 healthy ultra-marathon competitors using applanation tonometry (HDI CR-2000) before and after participation in a mountain trail running foot race ranging from 120-195 km which required between 20-40 continuous hours (31.2±6.8 h) to complete. There was no significant change in small artery compliance from baseline to post race follow-up (8.5±3.4-7.7±8.2 mL/mmHgx100, p=0.65), but large artery compliance decreased from 16.1±4.4 to 13.5±3.8 mL/mmHgx10 (p=0.003). Participation in extreme endurance exercise of prolonged duration was associated with acute reductions in large artery compliance, but the time course of this effect remains to be elucidated.

Comparing the Finapres and Caretaker systems for measuring pulse transit time before and after exercise.

We aimed to compare the Finapres system, which is designed for accurate intra-arterial amplitude measurement, to the Caretaker system, which is designed for temporal accuracy of intra-arterial measurement, in regard to measurement of pulse transit time (PTT) at baseline and following an endurance exercise session. Pulse transit time was evaluated between the R-wave of the ECG and the foot of the arterial waveform using either the Finapres (fpPTT) or Caretaker (ctPTT). 23 participants were measured before and after completion of endurance exercise. When comparing PTT values before and after an exercise intervention within devices, ctPTT was significantly different following exercise (P=0.03); however, the Finapres obtained values did not differ significantly. Before exercise, there was no significant relationship between devices, however, after exercise a significant moderate correlation was observed (r=0.45, P=0.02). Significant differences existed between ctPTT and fpPTT (P< 0.001). The Caretaker system appears to be more accurate at detecting changes in PTT occurring as a result of a single aerobic exercise session. This may be due to the servo-controller feedback loop in the waveform contour predicting algorithm within the Finapres system, which is not present in the Caretaker unit. The Finapres system also appears to have an inherent delay in pulse contour reporting.

Foam preparations for the treatment of ulcerative colitis.

Patients with ulcerative colitis uniformly have disease involving the distal colon. When patients have disease limited to the left colon or symptoms suggestive of active rectal inflammation, guidelines recommend topical rectal therapies as first-line agents either as monotherapy or in conjunction with oral products. Rectal delivery modalities offer the advantage of delivering high local concentrations of active medication to the site of maximal inflammation with minimization of systemic side effects. Methods of rectal administration include suppositories, liquid enemas and foams. Suppositories are limited to the treatment of rectal disease, and patients often have difficulty retaining the liquid enema secondary to its high volume and consistency. Rectal foams reliability extend to the descending and sigmoid colon with application. Foams are further characterized by increased viscosity, lower volumes, finer dispersion on the colonic mucosa, and increased adhesiveness to the colonic mucosa compared with liquid enemas. Additionally, rectal foam agents demonstrate equal efficacy to their liquid enema counterparts yet consistently yield better patient tolerance, lower incidence of side effects, and increased patient acceptability. Currently available agents include 5-aminosalicylic acid and corticosteroids, both first and newer generation. This review focuses on clinical trials assessing efficacy, tolerability, and patient preferences for these agents as well as describing the currently available rectal foam products.

Physiological fitness and health adaptations from purposeful training using off-road vehicles.

The purpose of this study was to evaluate fitness and health adaptations from a training program riding all-terrain vehicles (ATV) and off-road motorcycles (ORM) as the exercise stimulus. Participants (n = 58) were randomized to a control group (n = 12) or one of four experimental groups; 2 days/week ATV (n = 11), 2 days/week ORM (n = 12), 4 days/week ATV (n = 11), or 4 days/week ORM (n = 12). Aerobic fitness, musculoskeletal fitness, body composition, clinical health, and quality of life (QOL) were compared at baseline and following 6 weeks of training. In all riding groups, there were improvements in blood pressure (SBP = 9.4 ± 10.1, DBP = 5.8 ± 6.2 mmHg), fasting glucose (0.5 ± 0.7 mmol/l), subcutaneous adiposity (0.9 ± 1.1%), body mass (0.7 ± 2.7 kg), waist circumference (1.3 ± 2.5 cm), and isometric leg endurance (26 ± 44 s). All changes were of moderate to large magnitude (Cohen's d 0.52-0.94) with the exception of a small loss of body mass (Cohen's d = 0.27). Although changes occurred in the riding groups for aerobic power (2.9 ± 4.6 ml kg(-1) min(-1)), leg power (172 ± 486 w), and curl-ups (13.2 ± 22.7), these changes were not significantly different from the control group. No significant alterations occurred in resting heart rate, trunk flexibility, back endurance, hand grip strength, long jump, pull/push strength, or push-up ability as a result of training. Physical domain QOL increased in all 2 days/week riders but mental domain QOL increased in all ORM, but not ATV riders regardless of volume. Ambient carbon monoxide levels while riding (<30 ppm) were within safe exposure guidelines. Positive adaptations can be gained from a training program using off-road vehicle riding as the exercise stimulus.

Comparative performance of uncoated, self-expanding metal biliary stents of different designs in 2 diameters: final results of an international multicenter, randomized, controlled trial.

BACKGROUND: The Wallstent has remained the industry standard for biliary self-expanding metal stents (SEMSs). Recently, stents of differing designs, compositions, and diameters have been developed. OBJECTIVE: To compare the new nitinol 6-mm and 10-mm Zilver stents with the 10-mm stainless steel Wallstent and determine the mechanism of obstruction. DESIGN: Randomized, prospective, controlled study. SETTING: Nine centers experienced in SEMS placement during ERCP. PATIENTS: A total of 241 patients presenting between September 2003 and December 2005 with unresectable malignant biliary strictures at least 2 cm distal to the bifurcation. MAIN OUTCOME MEASUREMENT: Stent occlusions requiring reintervention and death. RESULTS: At interim analysis, a significant increase in occlusions was noted in the 6-mm Zilver group at the P = .04 level, resulting in arm closure but continued follow-up. Final study arms were 64, 88, and 89 patients receiving a 6-mm Zilver, 10-mm Zilver, and 10-mm Wallstent, respectively. Stent occlusions occurred in 25 (39.1%) of the patients in the 6-mm Zilver arm, 21 (23.9%) of the patients in the 10-mm Zilver arm, and 19 (21.4%) of the patients in the 10-mm Wallstent arm (P = .02). The mean number of days of stent patency were 142.9, 185.8, and 186.7, respectively (P = .057). No differences were noted in secondary endpoints, and the study was ended at the 95% censored study endpoints. Biopsy specimens of ingrowth occlusive tissue revealed that 56% were caused by benign epithelial hyperplasia. CONCLUSIONS: SEMS occlusions were much more frequent with a 6-mm diameter SEMS and equivalent in the two 10-mm arms despite major differences in stent design, material, and expansion, suggesting that diameter is the critical feature. Malignant tumor ingrowth produced only a minority of the documented occlusions.