Impact of walk advice alone or in combination with supervised or home-based structured exercise on patient-reported physical function and generic and disease-specific health related quality of life in patients with intermittent claudication, a secondary analysis in a randomized clinical trial.

BACKGROUND: Supervised exercise is an integral part of the recommended first-line treatment for patients with intermittent claudication (IC). By reflecting the patients' perspectives, patient-reported outcome measurements provide additional knowledge to the biomedical endpoints and are important outcomes to include when evaluating exercise interventions in patients with IC. We aimed to evaluate the one-year impact of three strategies: unsupervised Nordic pole walk advice (WA), WA + six months of home-based structured exercise (HSEP) or WA + six months of hospital-based supervised exercise (SEP) on health-related quality of life and patient-reported physical function in patients with IC. METHODS: This secondary exploratory analysis of a multi-center, randomized clinical trial compared three exercise strategies. The primary outcome of the secondary analysis was the one-year change in the 36-Item Short-Form (SF-36). Secondary outcomes were three- and six-months SF-36 changes alongside three, six- and 12-months changes in the disease-specific Vascular Quality of Life instrument (VascuQoL) and the Patient-Specific Functional Scale (PSFS). The Kruskal-Wallis test with Bonferroni-adjusted post-hoc tests were used for between-group comparisons. Effect size calculations were used to describe the size of observed treatment effects, and the clinical meaningfulness of observed changes in the VascuQoL summary score at one year was studied using established minimally important difference (MID) thresholds. RESULTS: A total of 166 patients with IC, mean age: 72.1 (SD 7.4) years, 41% women, were randomized. No significant between-group differences were observed over time for the SF-36 or the PSFS scores whereas some significant between-group differences were observed in the VascuQoL domain and summary scores over time, favoring SEP and/or HSEP over WA. The observed SF-36 and VascuQoL domain and summary score effect sizes were small to moderate, and many domain score effect sizes also remained unchanged over time. A significantly higher proportion of the patients in the SEP group reached the VascuQoL summary score MID of improvement in one year. CONCLUSION: Clinically important improvements were observed in SEP using the VascuQoL, while we did not observe any significant between-group differences using the SF-36. Whereas effect sizes for the observed changes over time were generally small, a significantly higher proportion of patients in SEP reached the VascuQoL MID of improvement. TRIAL REGISTRATION: NCT02341716, January 19, 2015 (retrospectively registered).

Cost-Effectiveness of Exercise Therapy in Patients with Intermittent Claudication-A Comparison of Supervised Exercise, Home-Based Structured Exercise, and Walk Advice from the SUNFIT Trial.

Hospital-based supervised exercise (SEP) is a guideline-recommended intervention for patients with intermittent claudication (IC). However, due to the limited availability of SEP, home-based structured exercise programs (HSEP) have become increasingly popular alongside the "go home and walk" advice. We evaluated the cost-effectiveness of walk advice (WA) with Nordic pole walking vs. SEP combined with WA or HSEP combined with WA. We used data from the SUNFIT RCT (NCT02341716) to measure quality-adjusted life-years (QALYs) over a 12-month follow-up, and economic costs were obtained from a hospital cost-per-patient accounting system. Incremental cost-effectiveness ratios (ICERs) were calculated, and uncertainty was assessed using nonparametric bootstrapping. The average health-care-cost per patient was similar in the WA (EUR 1781, n = 51) and HSEP (EUR 1820, n = 48) groups but higher in the SEP group (EUR 4619, n = 50, p-value < 0.01). Mean QALYs per patient during the follow-up were similar with no statistically significant differences. The findings do not support SEP as a cost-effective treatment for IC, as it incurred significantly higher costs without providing additional health improvements over WA with or without HSEP during the one-year observation period. The analysis also suggested that HSEP may be cost-effective compared to WA, but only with a 64% probability.

The Impact of Nordic Pole Walk Advice Alone or in Combination With Exercise Strategies on Daily Physical Activity in Patients With Intermittent Claudication: A Randomized Clinical Trial.

OBJECTIVE: The impact of exercise interventions on physical activity (PA) remains undetermined in intermittent claudication, which is why it is important to include objectively measured PA as an additional endpoint. The aim of this prespecified secondary analysis of a randomized clinical trial was to investigate the impact of unsupervised Nordic pole walk advice (WA) alone or in combination with hospital-based supervised exercise (SEP) or home-based structured exercise (HSEP) on PA in patients with intermittent claudication. METHODS: In total, 166 patients with intermittent claudication (mean age = 72 [SD = 7.4] y; 41% women) were randomized to 3 intermittent claudication-treatment strategies: WA, WA + SEP, or WA + HSEP. All patients received Nordic poles and standardized WA (≥30 min, 3 times weekly). Patients randomized to HSEP and SEP accepted participation in an additional 6-months exercise program. PA was measured with an accelerometer-based activPAL3 monitor for 7 days at baseline and at 3, 6, and 12 months. PA outcomes were steps per day, time spent within a stepping cadence ≥100 steps per minute, time spent upright, number of body transitions from sitting to standing, and number of sitting bouts of >30 minutes and >60 minutes. RESULTS: At 1 year, no intergroup differences were observed in any of the PA variables, whereas significant intergroup differences were observed at 3 months regarding time spent within a stepping time cadence ≥100 steps per minute. The mean change for HSEP (2.47 [SD = 10.85] min) was significantly different from the mean change for WA (-3.20 [SD = 6.24] min). At 6 months, the number of sitting bouts (>60 min) for SEP was significantly different from WA (mean change = 0.24 [SD = 0.69] vs -0.23 [SD = 0.81]). CONCLUSION: This study indicates that the addition of 6 months of HSEP or SEP does not improve PA at 1 year, as compared to unsupervised WA alone. Factors of importance for increasing PA in patients with intermittent claudication require further investigation. IMPACT: At the 1-year follow-up, the addition of intermittent claudication-tailored additional exercise strategies did not improve daily PA in patients with intermittent claudication compared with unsupervised Nordic pole WA alone. Future studies may explore the role of behavior change techniques to increase PA in this patient group.

Effectiveness of supervised exercise, home-based exercise, or walk advice strategies on walking performance and muscle endurance in patients with intermittent claudication (SUNFIT trial): a randomized clinical trial.

AIMS: Supervised exercise is a guideline-recommended treatment in intermittent claudication (IC). Hospital-based supervised exercise programmes (SEPs) are underutilized, while home-based structured exercise programmes (HSEPs) have attracted interest. The results from HSEP in IC are inconsistent and may confer no benefit over walk advice (WA) and be less effective than SEP. The aim of the study was to compare the effectiveness of best medical treatment, including Nordic pole WA alone, or WA + SEP or WA + HSEP for patients with IC. METHODS AND RESULTS: This three-armed, multicentre randomized clinical trial enrolled patients with IC; all patients received best medical treatment including walking poles and the advice of regular Nordic pole walking (WA). For HSEP and SEP, additional exercise programmes were provided. The primarily investigated hypothesis was a non-inferiority analysis of SEP vs. HSEP regarding the 6-min walk test (6MWT) maximum distance, with a pre-defined non-inferiority margin of 50 m. Supporting outcomes included muscle endurance tests and the walking impairment questionnaire. Outcomes were assessed at baseline, 3, 6, and 12 months by a blinded evaluator. Altogether 166 patients (mean age 72 years; 59% males) were randomized. In HSEP and SEP, 24 and 26% patients, respectively, were fully exercise adherent. All three groups improved pain-free walking distance over time, but there were no significant intergroup differences. The intergroup 6MWT difference between SEP and HSEP from 0 to 12 months was -11.6 m, 95% confidence interval: -36.4 to 13.0 m (i.e. within the pre-specified non-inferiority margin). CONCLUSION: The HSEP was non-inferior to SEP in patients with IC. There were no significant differences observed between the three groups at 1 year. REGISTRATION: ClinicialTrials.gov: NCT02341716.

A systematic review and meta-analysis of risks and benefits with breast reduction in the public healthcare system: priorities for further research.

BACKGROUND: There is no consensus for when publicly funded breast reduction is indicated and recommendations in guidelines vary greatly, indicating a lack of evidence and unequal access. The primary aim of this review was to examine risks and benefits of breast reduction to treat breast hypertrophy. Secondary aims were to examine how the studies defined breast hypertrophy and indications for a breast reduction. METHODS: A systematic literature search was conducted in PubMed, MEDLINE All, Embase, the Cochrane Library, and PsycInfo. The included articles were critically appraised, and certainty of evidence was assessed using the GRADE approach. Meta-analyses were performed when possible. RESULTS: Fifteen articles were included; eight reporting findings from four randomised controlled trials, three non-randomised controlled studies, three case series, and one qualitative study. Most studies had serious study limitations and problems with directness. Few of the studies defined breast hypertrophy. The studies showed significantly improved health-related quality of life and sexuality-related outcomes in patients who had undergone breast reduction compared with controls, as well as reduced depressive symptoms, levels of anxiety and pain. Most effect sizes exceeded the reported minimal important difference for the scale. Certainty of evidence for the outcomes above is low (GRADE ⊕ ⊕). Although four studies reported significantly improved physical function, the effect is uncertain (very low certainty of evidence, GRADE ⊕). None of the included studies reported data regarding work ability or sick leave. Three case series reported a 30-day mortality of zero. Reported major complications after breast reduction ranged from 2.4 to 14% and minor complications from 2.4 to 69%. CONCLUSION: There is a lack of high-quality studies evaluating the results of breast reduction. A breast reduction may have positive psychological and physical effects for women, but it is unclear which women benefit the most and which women should be offered a breast reduction in the public healthcare system. Several priorities for further research have been identified. PRE-REGISTRATION: The study is based on a Health Technology Assessment report, pre-registered and then published on the website of The Regional HTA Centre of Region Västra Götaland, Sweden.

Amputation-free survival, limb symptom alleviation, and reintervention rates after open and endovascular revascularization of femoropopliteal lesions in patients with chronic limb-threatening ischemia.

BACKGROUND: The optimal strategy for revascularization in chronic limb-threatening ischemia (CLTI) is not yet completely known and is still under debate. Endovascular treatment methods predominate despite limited evidence for their advantage. In this concurrent, prospective observational cohort study, we investigated outcomes after open and endovascular revascularization in the femoropopliteal segment for CLTI. METHODS: Between March 2011 and January 2015, there were 190 patients presenting with CLTI with the principal target lesion in the superficial femoral or popliteal segment who underwent endovascular intervention (n = 117) or bypass surgery (n = 73) and were observed prospectively. The choice of revascularization technique was based on international and local guidelines. All patients were observed for 2 years. The primary end point was amputation-free survival (AFS) assessed with Kaplan-Meier estimates; secondary end points included CLTI symptom alleviation rates and reintervention rates. A Cox proportional hazards regression model was used to investigate risk factors for amputation and death. RESULTS: AFS at 2 years was 59% in the endovascular group and 76% in the bypass group (P = .020). Kaplan-Meier survival analysis confirmed a significant difference in AFS, with mortality rate as the main driver for the observed intergroup AFS difference. In sequential multivariable regression analysis, the observed difference in AFS between the groups favored bypass surgery and remained significant after controlling for covariates of known prognostic importance (hazard ratio, 2.38; 95% confidence interval, 1.14-4.96). At 2 years, a higher proportion of patients subjected to bypass surgery remained free from ischemic rest pain, wounds, and gangrene (65% vs 45%; P = .009). The proportions of patients who underwent reintervention within 2 years were similar in the two groups (38% vs 39%; P = .90), but repeated reinterventions were more frequent in the bypass group. CONCLUSIONS: At 2 years, bypass surgery was associated with higher AFS than endovascular intervention, a finding that could not be explained only by differences in case mix. More patients who had bypass surgery were free from CLTI symptoms at both 1 year and 2 years after revascularization. Reinterventions to maintain patency were equally common after bypass and endovascular intervention.

Absence of Long-Term Benefit of Revascularization in Patients With Intermittent Claudication: Five-Year Results From the IRONIC Randomized Controlled Trial.

BACKGROUND: The long-term benefit of revascularization for intermittent claudication is poorly understood. The aim of this study was to investigate the long-term effectiveness and cost-effectiveness compared with a noninvasive approach. METHODS: The IRONIC trial (Invasive Revascularization or Not in Intermittent Claudication) randomized patients with mild-to-severe intermittent claudication to either revascularization + best medical therapy + structured exercise therapy (the revascularization group) or best medical therapy + structured exercise therapy (the nonrevascularization group). The health-related quality of life short form 36 questionnaire was primary outcome and disease-specific health-related quality of life (vascular quality of life questionnaire) and treadmill walking distances were secondary end points. Health-related quality of life has previously been reported superior in the revascularization group at 1- and 2-year follow-up. In this study, the 5-year results were determined. The cost-effectiveness of the treatment options was analyzed from a payer/healthcare standpoint. RESULTS: Altogether, 158 patients were randomized in a 1:1 ratio. Regarding the primary end point, no intergroup differences were observed for the short form 36 sum or domain scores from baseline to 5 years, except for the short form 36 role emotional domain score, with greater improvement in the nonrevascularization group (n=116, P=0.007). No intergroup differences were observed in the vascular quality of life questionnaire total and domain scores (n=116, NS) or in treadmill walking distances (n=91, NS). A revascularization strategy resulted in almost twice the cost per patient compared with a noninvasive treatment approach ($13 098 versus $6965, P=0.02). CONCLUSIONS: After 5 years of follow-up, a revascularization strategy had lost its early benefit and did not result in any long-term improvement in health-related quality of life or walking capacity compared to a noninvasive treatment strategy. Revascularization was not a cost-effective treatment option from a payer/healthcare point of view. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01219842.

Test-retest reliability, agreement, and minimal detectable change in the 6-minute walk test in patients with intermittent claudication.

OBJECTIVE: Standardized walk tests are important for objective assessment of walking distance in patients with intermittent claudication (IC). The 6-minute walk test (6MWT) has been suggested to correlate more closely than testing on a treadmill with everyday ambulatory function, but its measurement properties have hardly been studied in IC. The aim of this study was to determine the test-retest reliability, agreement, standard error of measurement (SEM), and minimal detectable change of the 6MWT in patients with IC. METHODS: This reliability and agreement study recruited 102 patients with stable IC (mean age, 72 ± 7.4 years; 43 women) from the vascular surgery outpatient clinic at Sahlgrenska University Hospital in Sweden. The patients performed the 6MWT twice, with at least 30 minutes of rest between tests. To determine test-retest reliability, the intraclass correlation coefficient was calculated. Bland-Altman plots were used to measure agreement. RESULTS: The mean walking distance in both test and retest was 397.8 m (standard deviation, 81.2 m; N = 100), and the individual walking distance varied from 175 to 600 m. Excellent test-retest reliability for the 6MWT (intraclass correlation coefficient, 0.95; 95% confidence interval, 0.9-0.97) was observed. The SEM was 16.6 m (95% confidence interval, 14.6-19.3), the SEM percentage was 4.2%, and the minimal detectable change was 46 m. Five observations (5%) were positioned outside the limits of agreement; there was a small proportional bias, and the scatter of values for differences decreased as the average values increased. CONCLUSIONS: The excellent test-retest reliability implies that it is sufficient for a patient with IC to perform the 6MWT once, at every test occasion. For the individual, an improvement or deterioration in maximum walking distance of >46 m after an intervention would be required to be 95% confident that the change is significant. Being a simple and clinically useful test, the 6MWT can be widely used to evaluate the effects of different interventions in patients with IC.

Echocardiographic assessment at rest and during stress in patients with intermittent claudication.

Objective. Skeletal muscle perfusion during walking relies on complex interactions between cardiac activity and vascular control mechanisms, why cardiac dysfunction may contribute to intermittent claudication (IC) symptoms. The study aims were to describe cardiac function at rest and during stress in consecutive IC patients, to explore the relations between cardiac function parameters and treadmill performance, and to test the hypothesis that clinically silent myocardial ischemia during stress may contribute to IC limb symptomatology. Design. Patients with mild to severe IC (n = 111, mean age 67 y, 52% females, mean treadmill distance 195 m) underwent standard echocardiography, dobutamine stress echocardiography (SE) and treadmill testing. The patient cohort was separated in two groups based on treadmill performance (HIGH and LOW performance). Results. Ten patients (9%) had regional wall motion abnormalities of which three had left ventricular ejection fraction <50% at standard echocardiography. A majority had lower than expected systolic- and diastolic ventricular volumes. LOW performers had smaller diastolic left ventricular volumes and lower global peak systolic velocity during dobutamine stress. No patient demonstrated significant cardiac dysfunction during dobutamine provocation that was not also evident at standard echocardiography. Conclusions. Most IC patients were without signs of ischemic heart disease or cardiac failure. The majority had small left ventricular volumes. The hypothesis that clinically silent myocardial ischemia impairing left ventricular function during stress may contribute to IC limb symptomatology was not supported.

Physical activity on prescription in accordance with the Swedish model increases physical activity: a systematic review.

OBJECTIVES: This study investigates the effects of the core elements of the Swedish model for physical activity on prescription (PAP) by evaluating studies that compared adults who received PAP with adults who did not receive PAP. All participants were adults identified by a healthcare professional as in need of increased physical activity. Primary outcome was level of physical activity. DESIGN: Systematic review. ELIGIBILITY CRITERIA: (1) Published 1999. (2) Systematic review, randomised controlled trial (RCT), non-RCT or case series (for adverse events). (3) ≥12 weeks' follow-up. (4) Performed in the Nordic countries. (5) Presented in English, Swedish, Norwegian or Danish. DATA SOURCES: Systematic searches in PubMed, Embase, the Cochrane Library, AMED, CINAHL and SweMed+ in September 2017. Included articles were evaluated using checklists to determine risk of bias. RESULTS: Nine relevant articles were included: seven RCTs, one cohort study and one case series. Primary outcome was reported in seven articles from six studies (five RCTs, one cohort study, 642 participants). Positive results were reported from three of the five RCTs and from the cohort study. No study reported any negative results. Swedish PAP probably results in an increased level of physical activity (GRADE⊕⊕⊕Ο). CONCLUSIONS: Although the number of the reviewed articles was relatively modest, this systematic review shows that PAP in accordance with the Swedish model probably increases the level of physical activity. As a model for exercise prescription, Swedish PAP may be considered as part of regular healthcare to increase physical activity in patients.

Home-based supervised exercise versus hospital-based supervised exercise or unsupervised walk advice as treatment for intermittent claudication: a systematic review.

OBJECTIVE: To evaluate the effects of home-based supervised exercise vs hospital-based supervised exercise, and the effects of home-based supervised exercise vs unsupervised "go home and walk advice" on daily life and corridor-walking capacity, health-related quality of life and patient-reported functional walking capacity in patients with intermittent claudication. DATA SOURCES: Systematic literature searches were conducted in PubMed, EMBASE, ProQuest, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), the Cochrane Library, and a number of Health Technology Assessment (HTA)-databases in October 2014. STUDY SELECTION: Randomized controlled trials and non-randomized controlled trials (> 100 patients) were considered for inclusion. DATA EXTRACTION: Data extraction and risk of bias assessment was performed independently and discussed in meetings. DATA SYNTHESIS: Seven randomized controlled trials and 2 non-randomized controlled studies fulfilled the inclusion criteria. The included studies had some, or major, limitations. CONCLUSION: Based on a low quality of evidence, home-based supervised exercise may lead to less improvement in maximum and pain-free walking distance, and in more improvement in daily life walking capacity, compared with hospital-based supervised exercise. Home-based supervised exercise may improve maximum and pain-free walking distance compared with "go home and walk advice" and result in little or no difference in health-related quality of life and functional walking capacity compared with hospital-based supervised exercise or "go home and walk advice". Further research is needed to establish the optimal exercise modality for these patients.

Improved quality of life after 1 year with an invasive versus a noninvasive treatment strategy in claudicants: one-year results of the Invasive Revascularization or Not in Intermittent Claudication (IRONIC) Trial.

BACKGROUND: The quality of evidence for invasive revascularization in intermittent claudication is low or very low. This prospective, randomized, controlled study tested the hypothesis that an invasive treatment strategy versus continued noninvasive treatment improves health-related quality of life after 1 year in unselected patients with intermittent claudication. METHODS AND RESULTS: After clinical and duplex ultrasound assessment, unselected patients with intermittent claudication requesting treatment for claudication were randomly assigned to invasive (n=79) or noninvasive (n=79) treatment groups. Primary end point was health-related quality of life after 1 year, assessed with Medical Outcomes Study Short Form 36 version 1 and Vascular Quality of Life Questionnaire, and secondary end points included walking distances on a graded treadmill. The Medical Outcomes Study Short Form 36 version 1 physical component summary (P<0.001) and 2 Medical Outcomes Study Short Form 36 version 1 physical subscales improved significantly more in the invasive versus the noninvasive treatment group. Overall, Vascular Quality of Life Questionnaire score (P<0.01) and 3 of 5 domain scores improved significantly more in the invasive versus the noninvasive treatment group. Intermittent claudication distance improved significantly in the invasive (+124 m) versus the noninvasive (+50 m) group (P=0.003), whereas the change in maximum walking distance was not significantly different between groups. CONCLUSIONS: An invasive treatment strategy improves health-related quality of life and intermittent claudication distance after 1 year in patients with stable lifestyle-limiting claudication receiving current medical management. Long-term follow-up data and health-economic assessments are warranted to further establish the role for revascularization in intermittent claudication.

Six-minute walk test closely correlates to "real-life" outdoor walking capacity and quality of life in patients with intermittent claudication.

OBJECTIVE: We used outdoor walking distance measured during 40 minutes as "real-life" outdoor walking capacity in 49 patients with intermittent claudication (IC). The outdoor walking distance was measured by a global positioning system application for a smartphone. The relationships of self-reported maximum walking distance (SR-MWD), the MWD on a graded treadmill test, and the 6-minute maximum walk distance (6MWD) vs outdoors walking capacity were investigated. Also studied were the associations of SR-MWD, MWD, and 6MWD with health-related quality of life assessed with the disease-specific instrument the Vascular Quality of Life Questionnaire (VascuQoL). METHODS: In this prospective observational cohort study, 49 IC patients underwent an outdoor walking capacity test for 40 minutes, and MWD and 6MWD were measured. SR-MWD was recorded, and all subjects completed the VascuQoL questionnaire. Associations between the different walk estimates and outdoor walking capacity and health-related quality of life were investigated by correlation analysis (Spearman ρ). RESULTS: Outdoor walking distance during 40 minutes was a median 2495 m (range, 1110-3300 m). SR-MWD correlated moderately and MWD correlated strongly to outdoor walking capacity (r = 0.56 and r = 0.65; P < .001, respectively). The 6MWD test showed the largest correlation to the outdoor walking capacity (r = 0.78; P < .001). The 6MWD was the only test that showed correlations with the VascuQoL sum score (r = 0.53; P < .01) and all of the domain scores, whereas SR-MWD and MWD showed weak correlations to the VascuQoL. CONCLUSIONS: The distance walked during the 6-minute walk test is closely correlated to outdoor walking capacity and health-related quality of life in IC patients. Our data support the use of 6MWD for routine clinical evaluation of walking capacity in IC patients.