Improvement In Pain-free Walking Distance Research Articles

Impact of BMI on Recovery and Quality of Life Post-Revascularization in Peripheral Arterial Disease Patients.

This study included 107 patients with peripheral arterial disease (PAD) undergoing revascularization and aimed to evaluate the effects of body mass index (BMI) on outcomes of quality of life (intermittent claudication questionnaire - ICQ), pain-free walking distance (PFWD), and maximum claudication distance (MCD). The study included 107 patients aged 18-80 years with PAD undergoing revascularization (average age 66±6.7 years; 82% men and 18% women, average BMI 28.02±4.35). The diagnosis of PAD was made based on medical opinion and an ankle-brachial index (ABI) value of <0.9. Methods used were BMI assessment, PFWD and MCD distances assessment (treadmill test using the Gardner-Skinner protocol), and quality of life assessment (ICQ). The examination was performed twice - at 1-5 days before the planned revascularization (classical surgery, angioplasty, or hybrid) and 3 months after the procedure. A statistically significant correlation was demonstrated between the improvement of PFWD, MCD, ICQ, and patients' BMI (P<0.01). The worst results were achieved by patients with II-degree obesity (PFWD improvement by an average 10.33±0.87, MCD of 21.67±3.25, ICQ of 14.01±0.60), while the best results were obtained by those with normal body weight (PFWD improvement by an average of 52.57±2.42, MCD of 137.20±22.30, ICQ of 21.18±0.54). Patients with a higher BMI have worse PFWD and MCD distances and quality of life 3 months after revascularization, which indicates the need to consider obesity when planning therapy. Further studies are needed to better understand the impact of BMI on the effectiveness of treatment and rehabilitation of patients with PAD.

Improvement of Pain-Free Walking Distance with Implementation of Treadmill Protocol

Peripheral arterial disease (PAD) may cause lower extremity pain that can impair activities of daily living. At a vascular clinic in rural New Mexico, peripheral arterial disease patients are managed but their symptoms continue to worsen so an evidence- based solution was sought. The purpose of this quantitative, quasi-experimental project was to determine if or to what degree the translation of McDermott et al.’s published research on the Gardner-Skinner Protocol will impact the pain-free walking distance when compared to current practice among peripheral arterial disease patients with intermittent claudication in a university activity center in rural New Mexico over four weeks. Dorothea Orem's self-care theory and Kurt Lewin's change theory provided the project's theoretical foundations. Data on walking distance was measured using the Six-Minute Walk Test in PAD patients (n = 12) and were compared at baseline and four weeks post-implementation of the intervention. A paired t-test showed no statistically significant difference in pain-free walking distance from baseline (M = 267.85, SD = 244.05) to post-intervention (M= 339.58, SD= 191.42), t (11) = -1.27, p= .23. Despite the lack of statistical significance, there was clinical significance in that the mean increase in pain-free walking distance increased by 70.83 feet. Therefore, the implementation of the Gardner-Skinner Protocol may improve walking distance in this population of patients. Recommendations are to continue the implementation and continue to analyze data for six months prior to dissemination.

Application of deep oscillation therapy in the treatment of peripheral arterial diseases

Intermittent claudication is a common symptom of peripheral arterial disease, affecting up to 50% of patients over the age of 50, which is characterized by pain, discomfort, and cramping in the leg muscles during physical activity. Intermittent claudication is a common symptom of lower extremity arterial disease (LEAD), which significantly impacts patients’ quality of life and drives healthcare costs. Current treatments for intermittent claudication are often inadequate, leading to a need for more effective treatments. Developing new treatments is critical to improve outcomes for patients and address the public health implications of LEAD. This study’s aim was to present the impact of comprehensive physiotherapy, conducted independently, with the supervision of a physiotherapist, for 14 weeks, on a patient with intermittent claudication caused by peripheral arterial disease. The therapy included bicycle training in a form of physical therapy at home, combined with deep oscillation therapy. Deep oscillation therapy involved the use of an electrostatic field with a frequency of 5 to 250 Hz. The field was applied following the lymphatic drainage methodology. In the discussed case, a statistically significant and favourable increase in the measured variables was observed, such as the increase of bone-brachial index from 0.65 to 0.8, the increase of tissue perfusion, measured by laser Doppler flowmetry, from 12.3% to 61%, depending on the measurement site, and the increase in pain-free walking distance by 451%. TcPO2 measurement in the affected leg increased from 31 to 48 mmHg. The use of physical therapy at home combined with deep oscillation showed improvements in pain-free walking distance, Ankle Brachial Index, and other measures in patients with peripheral arterial disease. Deep oscillation therapy demonstrated potential analgesic effects but also raised concerns about possible nerve damage. The study indicated that physical therapy at home might serve as an alternative to supervised exercise therapy, but it had limitations like a small sample size and lack of direct comparisons.

Outcome of posterior decompression for spinal epidural lipomatosis

BackgroundIn contrast to osteoligamentous lumbar stenosis (LSS), outcome of surgical treatment for spinal epidural lipomatosis (SEL) is still not well defined. We present risk factors for SEL and clinical long-term outcome data after surgical treatment for patients with pure SEL and a mixed-type pathology with combined SEL and LSS (SEL+LSS) compared to patients with pure LSS.MethodsFrom our prospective institutional database, we identified all consecutive patients who were surgically treated for newly diagnosed SEL (n = 31) and SEL+LSS (n = 26) between 2018 and 2022. In addition, a matched control group of patients with pure LSS (n = 30) was compared. Microsurgical treatment aimed for posterior decompression of the spinal canal. Study endpoints were outcome data including clinical symptoms at presentation, MR-morphological analysis, evaluation of pain-free walking distance, pain perception by VAS-N/-R scales, and patient’s satisfaction by determination of the Odom score.ResultsPatients with osteoligamentous SEL were significantly more likely to suffer from obesity (body mass index (BMI) of 30.2 ± 5.5 kg/m2, p = 0.03), lumbar pain (p = 0.006), and to have received long-term steroid therapy (p = 0.01) compared to patients with SEL+LSS and LSS. In all three groups, posterior decompression of the spinal canal resulted in significant improvement of these symptoms. Patients with SEL had a significant increase in pain-free walking distance during the postoperative course, at discharge, and last follow-up (FU) (p < 0.0001), similar to patients with SEL+LSS and pure LSS. In addition, patients with pure SEL and SEL+LSS had a significant reduction in pain perception, represented by smaller values of VAS-N and -R postoperatively and at FU, similar to patients with pure LSS. In uni- and multivariate analysis, domination of lumbar pain and steroid long-term therapy were significant characteristic risk factors for SEL.ConclusionsSurgical treatment of pure SEL and SEL+LSS allows significant improvement in pain-free walking distance and pain perception immediately postoperatively and in long-term FU, similar to patients with pure LSS.

Supervised exercise training improves cardiorespiratory fitness and reduces perioperative risk in peripheral artery disease patients with intermittent claudication.

This study examined to what extent supervised aerobic and resistance exercise combined with continued unsupervised exercise training improves cardiorespiratory fitness and corresponding perioperative risk in peripheral artery disease (PAD) patients with intermittent claudication. A total of 106 patients (77% male) were enrolled into the study, alongside 155 healthy non-PAD control participants. Patients completed supervised exercise therapy (aerobic and resistance exercises of the upper and lower limbs) twice a week for 10 weeks. Thereafter, 52 patients completed 12 weeks of an unsupervised tailored home-based exercise. Pain-free walking distance (PWD), maximum walking distance (MWD), peak oxygen uptake ([Formula: see text]) and perioperative risk were assessed before and after both exercise interventions. Patients were highly unconditioned relative to healthy controls ([Formula: see text]=11.9 vs 24.2ml/kg/min, p=<0.001) with 91% classified as high perioperative risk (peak oxygen uptake <15ml/kg/min). Supervised exercise increased PWD (+44±81m, p=<0.001), MWD (+44±71m, p=<0.001) and [Formula: see text] (+1.01±1.63ml/kg/min, p=<0.001) and lowered perioperative risk (91% to 85%, p=<0.001). When compared with supervised exercise, the improvements in PWD were maintained following unsupervised exercise (+11±91m vs supervised exercise, p=0.572); however, MWD and [Formula: see text] decreased (-15±48m, p=0.030 and -0.34±1.11ml/kg/min, p=0.030, respectively) and perioperative risk increased (+3%, p=<0.001) although still below baseline (p=<0.001). Supervised aerobic and resistance exercise training and, to a lesser extent, unsupervised tailored exercise improves walking capacity and cardiorespiratory fitness and reduces perioperative risk in PAD patients with intermittent claudication.

Supervised physical activity in patients with symptomatic peripheral arterial disease: protocol for a randomized clinical trial (ARTPERfit Study)

IntroductionPeripheral arterial disease (PAD) is a marker of cardiovascular morbidity, causing disability, loss of mobility and poor quality of life, manifesting clinically in the form of intermittent claudication (IC). Physical...

Propionyl-L-carnitine for intermittent claudication.

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis. Intermittent claudication is a symptomatic form of PAD that is characterized by pain in the lower limbs caused by chronic occlusive arterial disease. This pain develops in a limb during exercise and is relieved with rest. Propionyl-L-carnitine (PLC) is a drug that may alleviate the symptoms of PAD through a metabolic pathway, thereby improving exercise performance. The objective of this review is to determine whether propionyl-L-carnitine is efficacious compared with placebo, other drugs, or other interventions used for treatment of intermittent claudication (e.g. exercise, endovascular intervention, surgery) in increasing pain-free and maximum walking distance for people with stable intermittent claudication, Fontaine stage II. The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trials register to July 7, 2021. We undertook reference checking and contact with study authors and pharmaceutical companies to identify additional unpublished and ongoing studies. Double-blind randomized controlled trials (RCTs) in people with intermittent claudication (Fontaine stage II) receiving PLC compared with placebo or another intervention. Outcomes included pain-free walking performance (initial claudication distance - ICD) and maximal walking performance (absolute claudication distance - ACD), analyzed by standardized treadmill exercise test, as well as ankle brachial index (ABI), quality of life, progression of disease, and adverse events. Two review authors independently selected trials, extracted data, and evaluated trials for risk of bias. We contacted study authors for additional information. We resolved any disagreements by consensus. We performed fixed-effect model meta-analyses with mean differences (MDs) and 95% confidence intervals (CIs). We graded the certainty of evidence according to GRADE. We included 12 studies in this review with a total number of 1423 randomized participants. A majority of the included studies assessed PLC versus placebo (11 studies, 1395 participants), and one study assessed PLC versus L-carnitine (1 study, 26 participants). We identified no RCTs that assessed PLC versus any other medication, exercise, endovascular intervention, or surgery. Participants received PLC 1 grams to 2 grams orally (9 studies) or intravenously (3 studies) per day or placebo. For the comparison PLC versus placebo, there was a high level of both clinical and statistical heterogeneity due to study size, participants coming from different countries and centres, the combination of participants with and without diabetes, and use of different treadmill protocols. We found a high proportion of drug company-backed studies. The overall certainty of the evidence was moderate. For PLC compared with placebo, improvement in maximal walking performance (ACD) was greater for PLC than for placebo, with a mean difference in absolute improvement of 50.86 meters (95% CI 50.34 to 51.38; 9 studies, 1121 participants), or a 26% relative improvement (95% CI 23% to 28%). Improvement in pain-free walking distance (ICD) was also greater for PLC than for placebo, with a mean difference in absolute improvement of 32.98 meters (95% CI 32.60 to 33.37; 9 studies, 1151 participants), or a 31% relative improvement (95% CI 28% to 34%). Improvement in ABI was greater for PLC than for placebo, with a mean difference in improvement of 0.09 (95% CI 0.08 to 0.09; 4 studies, 369 participants). Quality of life improvement was greater with PLC (MD 0.06, 95% CI 0.05 to 0.07; 1 study, 126 participants). Progression of disease and adverse events including nausea, gastric intolerance, and flu-like symptoms did not differ greatly between PLC and placebo. For the comparison of PLC with L-carnitine, the certainty of evidence was low because this included a single, very small, cross-over study. Mean improvement in ACD was slightly greater for PLC compared to L-carnitine, with a mean difference in absolute improvement of 20.00 meters (95% CI 0.47 to 39.53; 1 study, 14 participants) or a 16% relative improvement (95% CI 0.4% to 31.6%). We found no evidence of a clear difference in the ICD (absolute improvement 4.00 meters, 95% CI -9.86 to 17.86; 1 study, 14 participants); or a 3% relative improvement (95% CI -7.4% to 13.4%). None of the other outcomes of this review were reported in this study. When PLC was compared with placebo, improvement in walking distance was mild to moderate and safety profiles were similar, with moderate overall certainty of evidence. Although In clinical practice, PLC might be considered as an alternative or an adjuvant to standard treatment when such therapies are found to be contraindicated or ineffective, we found no RCT evidence comparing PLC with standard treatment to directly support such use.

Lower Extremity Intermittent Negative Pressure for Intermittent Claudication. Follow-Up after 24 Weeks of Treatment

Treatment with lower extremity intermittent negative pressure (INP) of -40 mm Hg for one hour twice daily for 12 weeks, increases walking capacity in patients with intermittent claudication (IC). However, the effects of INP treatment beyond 12 weeks have not been elucidated. The aim of the present study was to investigate the clinical effects of INP treatment after 24 weeks in patients with IC. This was a follow-up study after a randomized sham-controlled trial, where patients randomized to the active treatment group were offered to continue treatment for 12 additional weeks (24 weeks in total). Treatment with -40 mm Hg INP was applied in a pressure chamber sealed around the lower leg, and the patients were instructed to treat themselves at home one hour in the morning and one hour in the evening. Pain free walking distance (PWD), maximal walking distance (MWD), resting ankle-brachial index (ABI) and post exercise ABI were measured at baseline, after 12 and 24 weeks. Ten out of 32 patients (31%) from the active treatment group in the initial trial were included in this follow-up study. At baseline, PWD was (mean ±SD) 151 ± 91 m and MWD was 362 ±159 m. There was a significant increase in both PWD and MWD after 24 weeks of treatment, compared to baseline (ANOVA; P= 0.006 and P= 0.012, respectively). Post hoc tests revealed that PWD increased significantly from baseline to 12 weeks (mean 81 m; 95% CI [6, 156]; P = 0.032), and that MWD increased significantly from 12 to 24 weeks (mean 145 m; 95% CI [22, 268]; P = 0.018). There were no significant changes in resting ABI or post exercise ABI during the 24-week treatment period (ANOVA; P= 0.157 and P= 0.450, respectively). Both PWD and MWD improved after treatment with - 40 mm Hg INP for one hour twice daily for 24 weeks, compared to baseline. The main improvement in PWD occurred during the first 12 weeks of treatment, whereas the main improvement in MWD occurred between 12 and 24 weeks of treatment.

Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Safety and Therapeutic Efficacy of Angiogenesis Induced by Intraarterial Autologous Bone Marrow–Derived Stem Cells in Patients with Severe Peripheral Arterial Disease

PurposeTo evaluate safety and efficacy of angiogenesis induced by intraarterial autologous bone marrow–derived stem cell (BMSC) injection in patients with severe peripheral arterial disease (PAD). Materials and MethodsEighty-one patients with severe PAD (77 men), including 56 with critical limb ischemia (CLI) and 25 with severe claudication, were randomized to receive sham injection (group A) or intraarterial BMSC injection at the site of occlusion (group B). Primary endpoints included improvement in ankle–brachial index (ABI) of > 0.1 and transcutaneous pressure of oxygen (TcPO2) of > 15% at mid- and lower foot at 6 mo. Secondary endpoints included relief from rest pain, > 30% reduction in ulcer size, and reduction in major amputation in patients with CLI and > 50% improvement in pain-free walking distance in patients with severe claudication. ResultsTechnical success was achieved in all patients, without complications. At 6 mo, group B showed more improvements in ABI of > 0.1 (35 of 41 [85.37%] vs 13 of 40 [32.50%]; P < .0001) and TcPO2 of > 15% at the midfoot (35 of 41 [85.37%] vs 17 of 40 [42.50%]; P = .0001] and lower foot (37 of 41 [90.24%] vs 19 of 40 [47.50%]; P < .0001). No patients with CLI underwent major amputation in group B, compared with 4 in group A (P = .0390). No significant difference was observed in relief from rest pain or > 30% reduction in ulcer size among patients with CLI or in > 50% improvement in pain-free walking distance among patients with severe claudication. ConclusionsIntraarterial delivery of autologous BMSCs is safe and effective in the management of severe PAD.

Pentoxifylline for intermittent claudication.

Intermittent claudication (IC) is a symptom of peripheral arterial disease (PAD) and is associated with high morbidity and mortality. Pentoxifylline, one of many drugs used to treat IC, acts by decreasing blood viscosity, improving erythrocyte flexibility, and promoting microcirculatory flow and tissue oxygen concentration. Many studies have evaluated the efficacy of pentoxifylline in treating people with PAD, but results of these studies are variable. This is the second update of a review first published in 2012. To determine the efficacy of pentoxifylline in improving the walking capacity (i.e. pain-free walking distance and total (absolute, maximum) walking distance) of people with stable intermittent claudication, Fontaine stage II. For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 28 January 2020. There were no language restrictions. We included all double-blind, randomised controlled trials (RCTs) comparing pentoxifylline versus placebo or any other pharmacological intervention in people with IC Fontaine stage II. Two review authors independently selected studies for inclusion, assessed the included studies, matched data and resolved disagreements by discussion. Review authors assessed the methodological quality of studies using the Cochrane 'Risk of bias' tool and collected results related to the outcomes of interest, pain-free walking distance (PFWD), total walking distance (TWD), ankle-brachial pressure index (ABI), quality of life (QoL) and side effects. Comparison of studies was based on duration and dose of pentoxifylline. We used GRADE criteria to assess the certainty of the evidence. We identified no new eligible studies for this update. This review includes 24 studies with 3377 participants. Seventeen studies compared pentoxifylline versus placebo. The seven remaining studies compared pentoxifylline with flunarizine (one study), aspirin (one study), Gingko biloba extract (one study), nylidrin hydrochloride (one study), prostaglandin E1 (two studies), and buflomedil and nifedipine (one study). Risk of bias for the individual studies was generally unclear because there was a lack of methodological reporting for many of the included studies, especially regarding randomisation and allocation methods. Most included studies did not provide adequate information to allow selective reporting to be judged and did not report blinding of assessors. Heterogeneity between included studies was considerable with regards to multiple variables, including duration of treatment, dose of pentoxifylline, baseline walking distance and participant characteristics; therefore, pooled analysis for comparisons which included more than one study, was not possible. Pentoxifylline compared to placebo Of 17 studies comparing pentoxifylline with placebo, 11 reported PFWD and 14 reported TWD; the difference in percentage improvement in PFWD for pentoxifylline over placebo ranged from -33.8% to 73.9% and in TWD ranged from 1.2% to 155.9%. It was not possible to pool the data of the studies because data were insufficient and findings from individual trials were unclear. Most included studies suggested a possible improvement in PFWD and TWD for pentoxifylline over placebo (both low-certainty evidence). The five studies which evaluated pre-exercise ABI comparing pentoxifylline and placebo found no evidence of a difference (moderate-certainty evidence). Two of the three studies that evaluated QoL between people who received pentoxifylline and placebo were larger studies that used validated QoL tools and generally found no evidence of a difference between groups. One small, short-term study, which did not specify which QoL tool was used, reported improved QoL in the pentoxifylline group (moderate-certainty evidence). Pentoxifylline generally was well tolerated; the most commonly reported side effects consisted of gastrointestinal symptoms such as nausea (low-certainty evidence). Certainty of the evidence from this review was low or moderate, with downgrading due to risk of bias concerns, inconsistencies between studies and the inability to evaluate imprecision because meta-analysis could not be undertaken. The seven remaining studies compared pentoxifylline with either flunarizine, aspirin, Gingko biloba extract, nylidrin hydrochloride, prostaglandin E1, or buflomedil and nifedipine; data were too limited to allow any meaningful conclusions to be made. There is a lack of high-certainty evidence for the effects of pentoxifylline compared to placebo, or other treatments, for IC. There is low-certainty evidence that pentoxifylline may improve PFWD and TWD compared to placebo, but no evidence of a benefit to ABI or QoL (moderate-certainty evidence). Pentoxifylline was reported to be generally well tolerated (low-certainty evidence). Given the large degree of heterogeneity between the studies, the role of pentoxifylline for people with IC Fontaine class II remains uncertain.

Remote Ischemic Pre-conditioning in the Management of Intermittent Claudication: A Pilot Randomized Controlled Trial

Animal data suggest that remote ischemic conditioning (RIC) can improve blood flow in ischemic limbs and, consequently, may benefit claudication patients. Supervised exercise is the preferred first-line intervention for patients with intermittent claudication (IC) but is constrained by limited availability and logistical issues, particularly in rural settings. The aim of this study is to evaluate remote ischemic pre-conditioning in the management of intermittent claudication patients. We undertook a randomized clinical trial to evaluate RIC's effect in claudication patients. Stable IC patients were randomly allocated to receive RIC alone, structured exercise (SE) alone, RIC plus SE, or to a control group which received standard advice and risk factor modification. Patients received their intervention over a 28-day period. RIC patients attended an RIC clinic every 3-4days to undergo 4 cycles of 5-min upper limb ischemia followed by 5-min reperfusion induced with a standard blood pressure cuff. Forty-five patients were randomized, of whom 40 completed the trial (10 patients per group). The RIC alone, SE alone, and RIC plus SE groups all demonstrated significant improvements in pain-free walking distance and ankle-brachial pressure indices at 30days. There were no differences in the magnitude of improvements between the groups. Compared with standard care RIC is promising as a home-delivered intervention. It appears to be equivalent to SE in the treatment of IC, with no apparent additive benefit to combining the 2 interventions in this small size sample. Large-scale randomized controlled trial is needed for validation.

Exercise Rehabilitation for Peripheral Artery Disease: A REVIEW.

To summarize evidence regarding exercise therapy for people with lower extremity peripheral artery disease (PAD). Literature was reviewed regarding optimal strategies for delivering exercise interventions for people with PAD. Randomized trial evidence and recent studies were emphasized. Randomized clinical trial evidence consistently demonstrates that supervised treadmill exercise improves treadmill walking performance in people with PAD. A meta-analysis of 25 randomized trials (1054 participants) concluded that supervised treadmill exercise was associated with 180 m of improvement in maximal treadmill walking distance and 128 m of improvement in pain-free walking distance compared with a control group. Three randomized trials of 493 patients with PAD demonstrated that home-based walking exercise interventions that incorporate behavioral change techniques improve walking ability in patients with PAD. Furthermore, evidence suggests that home-based walking exercise improves the 6-min walk more than supervised treadmill exercise. Upper and lower extremity ergometry also significantly improved walking endurance in PAD. The Centers for Medicare & Medicaid Services recently determined that Medicare would cover 12 wk (36 sessions) of supervised treadmill exercise for patients with PAD. Supervised treadmill exercise and home-based walking exercise each improve walking ability in patients with PAD. The availability of insurance coverage for supervised treadmill exercise for patients with PAD will make supervised treadmill exercise more widely available and accessible. Home-based exercise that incorporates behavioral change technique is an effective alternative for patients unwilling or unable to attend 3 supervised exercise sessions per week.

Exercise for intermittent claudication.

Background Exercise programmes are a relatively inexpensive, low-risk option compared with other more invasive therapies for leg pain on walking (intermittent claudication (IC)). This is an update of a review first published in 1998. Objectives The prime objective of this review was to determine whether an exercise programme in people with intermittent claudication was effective in alleviating symptoms and increasing walking treadmill distances and walking times. Secondary objectives were to determine whether exercise was effective in preventing deterioration of underlying disease, reducing cardiovascular events and improving quality of life. Search methods For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2013) and CENTRAL (2013, Issue 8). Selection criteria Randomised controlled trials of an exercise regimen versus control or versus medical therapy in people with IC due to peripheral arterial disease. Any exercise programme or regimen used in the treatment of intermittent claudication was included, such as walking, skipping and running. Inclusion of trials was not affected by the duration, frequency or intensity of the exercise programme. Outcome measures collected included treadmill walking distance (time to onset of pain or pain-free walking distance and maximum walking time or maximal walking distance), ankle brachial index (ABI), quality of life, morbidity or amputation; if none of these were reported the trial was not included in this review. Data collection and analysis Two review authors independently extracted data and assessed trial quality. Main results Eleven additional studies were included in this update making a total of 30 trials which met the inclusion criteria, involving a total of 1816 participants with stable leg pain. The follow-up period ranged from two weeks to two years. The types of exercise varied from strength training to polestriding and upper or lower limb exercises; generally supervised sessions were at least twice a week. Most trials used a treadmill walking test for one of the outcome measures. Quality of the included trials was moderate, mainly due to an absence of relevant information. The majority of trials were small with 20 to 49 participants. Twenty trials compared exercise with usual care or placebo, the remainder of the trials compared exercise to medication (pentoxifylline, iloprost, antiplatelet agents and vitamin E) or pneumatic calf compression; people with various medical conditions or other pre-existing limitations to their exercise capacity were generally excluded. Overall, when taking the first time point reported in each of the studies, exercise significantly improved maximal walking time when compared with usual care or placebo: mean difference (MD) 4.51 minutes (95% confidence interval (CI) 3.11 to 5.92) with an overall improvement in walking ability of approximately 50% to 200%. Walking distances were also significantly improved: pain-free walking distance MD 82.29 metres (95% CI 71.86 to 92.72) and maximum walking distance MD 108.99 metres (95% CI 38.20 to 179.78). Improvements were seen for up to two years, and subgroup analyses were performed at three, six and 12 months where possible. Exercise did not improve the ABI (MD 0.05, 95% CI 0.00 to 0.09). The effect of exercise, when compared with placebo or usual care, was inconclusive on mortality, amputation and peak exercise calf blood flow due to limited data. No data were given on non-fatal cardiovascular events. Quality of life measured using the Short Form (SF)-36 was reported at three and six months. At three months, physical function, vitality and role physical all significantly improved with exercise, however this was a limited finding as this measure was only reported in two trials. At six months five trials reported outcomes of a significantly improved physical summary score and mental summary score secondary to exercise. Only two trials reported improvements in other domains, physical function and general health. Evidence was generally limited for exercise compared with antiplatelet therapy, pentoxifylline, iloprost, vitamin E and pneumatic foot and calf compression due to small numbers of trials and participants. Authors' conclusions Exercise programmes are of significant benefit compared with placebo or usual care in improving walking time and distance in people with leg pain from IC who were considered to be fit for exercise intervention.

Safety and Efficacy of Repeated Bone Marrow Mononuclear Cell Therapy in Patients with Critical Limb Ischemia in a Pilot Randomized Controlled Trial.

Critical limb ischemia is a manifestation of peripheral arterial disease characterized by insufficient arterial blood flow for maintaining tissue viability in the lower extremities. Therapeutic angiogenesis is used for peripheral arterial disease patients who are not candidates for surgical revascularization or radiological intervention. There is accumulating evidence for the beneficial impact of autologous bone marrow mononuclear cell transplantation for treatment of critical limb ischemia in humans. This study aims to investigate the safety and efficacy of repeated bone marrow mononuclear cell injections in comparison with a single bone marrow mononuclear cell injection in critical limb ischemia patients. Patients with critical limb ischemia (n = 22) were randomized (http://clinicaltrials.gov/ct2 show/NCT01480414) to receive either a single (n = 11) or four (n = 11) intramuscular injections of bone marrow mononuclear cells as a cell therapy product. There were no reported adverse events during the 24-week follow-up period after cell delivery. Efficacy assessment indicated that after cell injections, there was significant improvement in Ankle-Brachial Index, Visual Analog Scale, pain-free walking distance, and Wagner stage as well as reduction in ulcer size. There was no significant difference between the two groups in terms of clinical parameters. However, by the 24th week the pain-free walking distance improved significantly in the group who received four injections of cells. Favorable clinical outcomes strongly indicate the long-term benefit of bone marrow mononuclear cell transplantation, either as one or several injections, for retrieval from critical limb ischemia. Repeated cell injections have shown increased improvement of pain-free walking distance in patients. These findings warrant further exploration in later-phase clinical trials with repeated injections.

Induction of Angiogenesis by a Type III Phosphodiesterase Inhibitor, Cilostazol, Through Activation of Peroxisome Proliferator-Activated Receptor-γ and cAMP Pathways in Vascular Cells.

Peripheral arterial disease is highly prevalent in the elderly and in the subjects with cardiovascular risk factors such as diabetes. Approximately 2% to 4% of those affected with peripheral arterial disease commonly complain of intermittent claudication. Cilostazol, a type III phosphodiesterase inhibitor, is the only Food and Drug Administration-approved drug for the treatment of intermittent claudication. Cilostazol has been shown to be beneficial for the improvement of pain-free walking distance in patients with intermittent claudication in a series of randomized clinical trials. However, the underlying mechanism how cilostazol improved intermittent claudication symptoms is still unclear. In this study, the effect of cilostazol on ischemic leg was investigated in mouse ischemic hindlimb model. Administration of cilostazol significantly increased the expression of hepatocyte growth factor (HGF), vascular endothelial growth factor, angiopoietin-1, and peroxisome proliferator-activated receptor-γ in vasculature. The capillary density in ischemic leg was also significantly increased in cilostazol treatment group when compared with control and aspirin treatment group. However, an increase in capillary density and the expression of growth factors was almost completely abolished by coadministration of HGF-neutralizing antibody, suggesting that cilostazol enhanced angiogenesis mainly through HGF. In vitro experiment revealed that cilostazol treatment increased HGF production in vascular smooth muscle cells via 2 major pathways: peroxisome proliferator-activated receptor-γ and cAMP pathways. Our data suggest that the favorable effects of cilostazol on ischemic leg might be through the angiogenesis through the induction of HGF via peroxisome proliferator-activated receptor-γ and cAMP pathways.

Pentoxifylline for intermittent claudication.

Intermittent claudication (IC) is a symptom of peripheral arterial disease (PAD) and is associated with high morbidity and mortality. Pentoxifylline, one of many drugs used to treat IC, acts by decreasing blood viscosity, improving erythrocyte flexibility and promoting microcirculatory flow and tissue oxygen concentration. Many studies have evaluated the efficacy of pentoxifylline in treating individuals with PAD, but results of these studies are variable. This is an update of a review first published in 2012. To determine the efficacy of pentoxifylline in improving the walking capacity (i.e. pain-free walking distance and total (absolute, maximum) walking distance) of individuals with stable intermittent claudication, Fontaine stage II. For this update, the Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched April 2015) and the Cochrane Register of Studies (2015, Issue 3). All double-blind, randomised controlled trials (RCTs) comparing pentoxifylline versus placebo or any other pharmacological intervention in patients with IC Fontaine stage II. Two review authors separately assessed included studies,. matched data and resolved disagreements by discussion. Review authors assessed the methodological quality of studies by using the Cochrane 'Risk of bias' tool and collected results related to pain-free walking distance (PFWD) and total walking distance (TWD). Comparison of studies was based on duration and dose of pentoxifylline. We included in this review 24 studies with 3377 participants. Seventeen studies compared pentoxifylline versus placebo. In the seven remaining studies, pentoxifylline was compared with flunarizine (one study), aspirin (one study), Gingko biloba extract (one study), nylidrin hydrochloride (one study), prostaglandin E1 (two studies) and buflomedil and nifedipine (one study). The quality of the evidence was generally low, with large variability in reported findings.. Most included studies did not report on random sequence generation and allocation concealment, did not provide adequate information to allow selective reporting to be judged and did not report blinding of assessors. Heterogeneity between included studies was considerable with regards to multiple variables, including duration of treatment, dose of pentoxifylline, baseline walking distance and participant characteristics; therefore, pooled analysis was not possible.Of 17 studies comparing pentoxifylline with placebo, 14 reported TWD and 11 reported PFWD; the difference in percentage improvement in TWD for pentoxifylline over placebo ranged from 1.2% to 155.9%, and in PFWD from -33.8% to 73.9%. Testing the statistical significance of these results generally was not possible because data were insufficient. Most included studies suggested improvement in PFWD and TWD for pentoxifylline over placebo and other treatments, but the statistical and clinical significance of findings from individual trials is unclear. Pentoxifylline generally was well tolerated; the most commonly reported side effects consisted of gastrointestinal symptoms such as nausea. Given the generally poor quality of published studies and the large degree of heterogeneity evident in interventions and in results, the overall benefit of pentoxifylline for patients with Fontaine class II intermittent claudication remains uncertain. Pentoxifylline was shown to be generally well tolerated.Based on total available evidence, high-quality data are currently insufficient to reveal the benefits of pentoxifylline for intermittent claudication.

Short-Term Outcomes of the Subchondroplasty Procedure for the Treatment of Bone Marrow Edema Lesions in Patients with Knee Osteoarthritis

Objectives:To determine the short-term outcomes, effectiveness and perception of the subchondroplasty (SCP) procedure in patients with radiographic evidence of bone marrow edema (BME) in the setting of knee osteoarthritis (OA).Methods:A retrospective chart review in conjunction with a follow-up questionnaire was conducted on fifty patients with radiographic evidence of BME lesions who underwent the SCP procedure performed at a single academic medical institution. All patients failed prior conservative measures, including medications, injections, physical therapy, and bracing. The questionnaire focused on symptoms before and after the procedure, the perception of the procedure, any other interventions performed after the procedure, and willingness to undergo SCP again.Results:The average patient age was 55 years (range 36-82 years) and 53.2% of patients were male. The average follow-up period was 14.6 months (range 12.9-25.1 months). Preliminary data from 50 patients demonstrated an average 4.7 point improvement in pain on a 10 point visual analog scale (pre-SCP 8.3, post-SCP 3.6). Eighty-eight percent (44 of 50) of patients experienced improvement in their pain and 72% (36 of 50) experienced improvement in pain-free walking distance. Forty-eight percent (24 of 50) of patients required additional interventions: eighteen received cortisone or hyaluronic acid injections, two required serial aspirations, and four went on to total knee arthroplasty. The average satisfaction level was 7.8 on a 10 point scale. Seventy-eight percent (39 of 50) of patients stated they would undergo SCP again and 86% (43 of 50) would recommend the procedure to a friend or family member.Conclusion:SCP is an effective treatment modality in the management of patients with knee OA and BME lesions. The goal of the procedure is to provide enduring pain relief caused by BME, hopefully delaying the need for TKA in this select patient population. Future studies are necessary to evaluate the long-term outcomes of SCP.

Effectiveness of Intravenous Ilomedin Infusion and Smoking Cessation in the Treatment of Acutely Symptomatic Buerger Disease

We assessed the effectiveness of iloprost treatment in the management of symptomatic Buerger disease (BD) and assessed smoking cessation compliance, based on a single-center experience. Thirteen patients with BD were treated with sessions of intravenous (IV) Ilomedin infusion. At 1-year follow-up, pain status alteration, number of analgesics required, ankle-brachial index (ABI) change, compliance with supervised smoking cessation, and amputation-free rate were recorded. The pain status improved considerably according to a visual analog scale, the number of analgesics required was significantly reduced, and all patients improved their pain-free walking distance, the ABI, and their self-reported quality of life. Only 2 patients required minor amputations. Combination of IV Ilomedin infusion, supervised smoking cessation, and a specific follow-up protocol may lead to improvement in pain-free walking distance, pain status, quality of life, and substantial reduction in amputation risk.

Predictors of Improved Quality of Life and Claudication in Patients Undergoing Spinal Cord Stimulation for Critical Lower Limb Ischemia

The aim of this study was to determine predictors of improved quality of life and claudication in patients undergoing spinal cord stimulation (SCS) for critical lower limb ischemia. We retrospectively analyzed 101 consecutive patients with few meter claudication and nonhealing ulcer who underwent definitive SCS. These patients were selected among 274 SCS patients treated at our center from 1995 to 2012. All presented with non-reconstructable critical leg ischemia (NR-CLI) and underwent supervised exercise therapy, best medical care and regular ulcers standard or advanced medications for at least 1 month before SCS implantation. We measured self-perceived quality of life using the SF-36 questionnaire. Patients with an improved walking distance of at least 30 meters after SCS had significant improvement on SF-36 questionnaire scores. We considered 30 meters as the cut-off for clinically significant improvement in pain-free walking distance, and we defined this value as functional success. Logistic regression was applied to assess baseline and other patient variables as possible predictors of functional success. Neither perioperative mortality nor significant complications were found. At a median follow-up of 69 months (range 1-202 months), mortality, major amputation, and minor amputation were 8.9%, 5.9%, and 6.9%, respectively. Functional clinical success was reported in 25.7% of cases. Independent predictors of functional success at univariate analysis included delay between the onset of the ulcer and SCS (P < 0.001) and the pain-free walking distance before SCS (P < 0.002). The only predictive factor of functional success at multivariate analysis was the delay between the onset of ulcer and SCS (median delay in patients with and without functional success was 3 and 15 months, respectively). In particular, comparable to pain-free walking distance before SCS, the success rate decreased by 40% for each month elapsed from onset of ulcer to SCS. In our series of patients who underwent SCS, reduced delay between the onset of ulcer and SCS was associated with improved quality of life and walking distance. Larger series are required to confirm these data and to assess clinical implications.

Prostanoids for intermittent claudication

Peripheral arterial disease (PAD) is a common cause of morbidity in the general population. While numerous studies have established the efficacy of prostanoids in PAD stages III and IV, the question of the role of prostanoids as an alternative or additive treatment in patients suffering from intermittent claudication (PAD II) has not yet been clearly answered. This is an update of a Cochrane Review first published in 2004. To determine the effects of prostanoids in patients with intermittent claudication (IC) Fontaine stage II. For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched January 2013) and CENTRAL (2012, Issue 12). Clinical trials databases were searched for details of ongoing or unpublished studies. In addition, reference lists of relevant articles were checked. Randomised clinical trials of prostanoids versus placebo or alternative ('control') treatment in people with intermittent claudication were considered for inclusion. Two authors independently assessed trial quality and extracted data. Primary outcomes included pain-free walking distance (PFWD) and maximum walking distance (MWD), presented as mean change in walking distance during the course of the trial (% improvement) and as final walking distance (that is walking distance, in metres, after treatment) for the prostanoid and control groups. Eighteen trials with a total of 2773 patients were included (16 in the original review and a further two in this update). As the majority of trials did not report standard deviations for the primary PFWD and MWD outcomes, it was often not possible to test for the statistical significance of any improvements in walking distance between groups. The quality of individual trials was variable and usually unclear due to insufficient reporting information. Comparison between trials was hampered by the use of different treadmill testing protocols, including different walking speeds and gradients. Such limitations in the data and the trial heterogeneity meant it was not possible to meaningfully pool results by meta-analysis.Four trials compared prostaglandin E1 (PGE1) with placebo; individual trials showed significant increases in walking distances with administration of PGE1 and in several trials the walking capacity remained increased after termination of treatment. Compared with pentoxifylline, PGE1 was associated with a higher final PFWD and MWD but these results were based on final walking distances rather than changes in walking distance from baseline. When PGE1 was compared with other treatments including laevadosin, naftidrofuryl and L-arginine, improvements in walking distances over time were observed for both PGE1 and the alternative treatment, but it was not possible from the data available to analyse statistically whether or not one treatment was more effective than the other.Six studies compared various preparations of prostacyclins (PGI2) with placebo. In one study using three different dosages of iloprost, PFWD and MWD appeared to increase in a dose-dependent manner; iloprost was associated with headache, pain, nausea and diarrhoea, leading to a higher rate of treatment withdrawal. Of three studies using beraprost sodium, one showed an improvement in PFWD and MWD compared with placebo while two showed no significant benefit. Beraprost sodium was associated with an increased incidence of drug-related adverse events. Of two studies on taprostene, the results of one in particular must be interpreted with caution due to an imbalance in walking capacity at baseline.Comprehensive, high quality data on outcomes such as quality of life, ankle brachial index, venous occlusion plethysmography and haemorrheological parameters were lacking. Whilst results from some individual studies suggested a beneficial effect of PGE1, the quality of these studies and of the overall evidence available is insufficient to determine whether or not patients with intermittent claudication derive clinically meaningful benefit from the administration of prostanoids. Further well-conducted randomised, double blinded trials with a sufficient number of participants to provide statistical power are required to answer this question.