Kunwarjit Sangla

Effects of a long term exercise program on lower limb mobility, physiological responses, walking performance and physical activity levels in patients with peripheral arterial disease

OBJECTIVE The purpose of the study was to examine the effects of a 12-month exercise program on lower limb mobility (temporal-spatial gait parameters and gait kinematics), walking performance, peak physiological responses, and physical activity levels in individuals with symptoms of intermittent claudication due to peripheral arterial disease (PAD-IC). METHODS Participants (n = 21) with an appropriate history of PAD-IC, ankle-brachial pressure index (ABI) <0.9 in at least one leg and a positive Edinburgh claudication questionnaire response were prospectively recruited. Participants were randomly allocated to either a control PAD-IC group (CPAD-IC) (n = 11) that received standard medical therapy and a treatment PAD-IC group (TPAD-IC) (n = 10), which also took part in a 12-month supervised exercise program. A further group of participants (n = 11) free of PAD (ABI >0.9) and who were non-regular exercisers were recruited from the community to act as age and mass matched controls (CON). Lower limb mobility was determined via two-dimensional video motion analysis. A graded treadmill test was used to assess walking performance and peak physiological responses to exercise. Physical activity levels were measured via a 7-day pedometer recording. Differences between groups were analyzed via repeated measures analysis of variance (ANOVA). RESULTS The 12-month supervised exercise program had no significant effect on lower limb mobility, peak physiological responses, or physical activity levels in TPAD-IC compared with CPAD-IC participants. However, the TPAD-IC participants demonstrated significantly greater walking performance (171% improvement in pain free walking time and 120% improvement in maximal walking time compared with baseline). CONCLUSION The results of this study confirm that a 12-month supervised exercise program will result in improved walking performance, but does not have an impact on lower limb mobility, peak physiological responses, or physical activity levels of PAD-IC patients.

Biomechanical characteristics of peripheral diabetic neuropathy: A systematic review and meta-analysis of findings from the gait cycle, muscle activity and dynamic barefoot plantar pressure

BACKGROUND Diabetic peripheral neuropathy is an important cause of foot ulceration and limb loss. This systematic review and meta-analysis investigated the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and dynamic plantar pressures. METHODS Electronic databases were searched systematically for articles reporting the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and plantar pressures. Searches were restricted to articles published between January 2000 and April 2012. Outcome measures assessed included spatiotemporal parameters, lower limb kinematics, kinetics, muscle activation and plantar pressure. Meta-analyses were carried out on all outcome measures reported by ≥3 studies. FINDINGS Sixteen studies were included consisting of 382 neuropathy participants, 216 diabetes controls without neuropathy and 207 healthy controls. Meta-analysis was performed on 11 gait variables. A high level of heterogeneity was noted between studies. Meta-analysis results suggested a longer stance time and moderately higher plantar pressures in diabetic peripheral neuropathy patients at the rearfoot, midfoot and forefoot compared to controls. Systematic review of studies suggested potential differences in the biomechanical characteristics (kinematics, kinetics, EMG) of diabetic neuropathy patients. However these findings were inconsistent and limited by small sample sizes. INTERPRETATION Current evidence suggests that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait. Firm conclusions are hampered by the heterogeneity and small sample sizes of available studies.

Determinants of Endothelial Function in a Cohort of Patients with Peripheral Artery Disease

Objectives: Endothelial dysfunction assessed by brachial artery flow-mediated dilatation (FMD) has been associated with cardiovascular events. There have been relatively few studies examining FMD or other measures of endothelial function in patients with peripheral artery disease (PAD). The aim of this study was to examine determinants of FMD in a homogenous cohort of patients with PAD. Methods: We prospectively assessed patients presenting with life style-limiting intermittent claudication to establish the presence of cardiovascular risk factors, obesity and metabolic syndrome. Fasting serum was assayed for lipids, C-reactive protein, adiponectin, leptin, resistin and osteoprotegerin (OPG). FMD was measured by high-resolution ultrasound. Results: Serum concentrations of OPG were elevated in patients with obesity and metabolic syndrome. FMD was impaired in patients with obesity and metabolic syndrome and negatively correlated with serum concentrations of OPG. By multiple regression analysis, metabolic syndrome was independently associated with impaired FMD after adjustment for age, smoking, ischaemic heart disease, cerebrovascular disease and severity of PAD. Conclusions: Our findings suggest that metabolic syndrome is an important determinant of endothelial function in patients with PAD, and OPG may be a useful biomarker of this effect.

Effects of a 6-month exercise program pilot study on walking economy, peak physiological characteristics, and walking performance in patients with peripheral arterial disease

The purpose of this study was to examine the effects of a 6-month exercise program on submaximal walking economy in individuals with peripheral arterial disease and intermittent claudication (PAD-IC). Participants (n = 16) were randomly allocated to either a control PAD-IC group (CPAD-IC, n = 6) which received standard medical therapy, or a treatment PAD-IC group (TPAD-IC; n = 10) which took part in a supervised exercise program. During a graded treadmill test, physiological responses, including oxygen consumption, were assessed to calculate walking economy during submaximal and maximal walking performance. Differences between groups at baseline and post-intervention were analyzed via Kruskal–Wallis tests. At baseline, CPAD-IC and TPAD-IC groups demonstrated similar walking performance and physiological responses. Postintervention, TPAD-IC patients demonstrated significantly lower oxygen consumption during the graded exercise test, and greater maximal walking performance compared to CPAD-IC. These preliminary results indicate that 6 months of regular exercise improves both submaximal walking economy and maximal walking performance, without significant changes in maximal walking economy. Enhanced walking economy may contribute to physiological efficiency, which in turn may improve walking performance as demonstrated by PAD-IC patients following regular exercise programs.

Plantar Pressure in Diabetic Peripheral Neuropathy Patients with Active Foot Ulceration, Previous Ulceration and No History of Ulceration: A Meta-Analysis of Observational Studies

Aims Elevated dynamic plantar pressures are a consistent finding in diabetes patients with peripheral neuropathy with implications for plantar foot ulceration. This meta-analysis aimed to compare the plantar pressures of diabetes patients that had peripheral neuropathy and those with neuropathy with active or previous foot ulcers. Methods Published articles were identified from Medline via OVID, CINAHL, SCOPUS, INFORMIT, Cochrane Central EMBASE via OVID and Web of Science via ISI Web of Knowledge bibliographic databases. Observational studies reporting barefoot dynamic plantar pressure in adults with diabetic peripheral neuropathy, where at least one group had a history of plantar foot ulcers were included. Interventional studies, shod plantar pressure studies and studies not published in English were excluded. Overall mean peak plantar pressure (MPP) and pressure time integral (PTI) were primary outcomes. The six secondary outcomes were MPP and PTI at the rear foot, mid foot and fore foot. The protocol of the meta-analysis was published with PROPSERO, (registration number CRD42013004310). Results Eight observational studies were included. Overall MPP and PTI were greater in diabetic peripheral neuropathy patients with foot ulceration compared to those without ulceration (standardised mean difference 0.551, 95% CI 0.290–0.811, p<0.001; and 0.762, 95% CI 0.303–1.221, p = 0.001, respectively). Sub-group analyses demonstrated no significant difference in MPP for those with neuropathy with active ulceration compared to those without ulcers. A significant difference in MPP was found for those with neuropathy with a past history of ulceration compared to those without ulcers; (0.467, 95% CI 0.181– 0.753, p = 0.001). Statistical heterogeneity between studies was moderate. Conclusions Plantar pressures appear to be significantly higher in patients with diabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic neuropathy without a history of ulceration. More homogenous data is needed to confirm these findings.

Burkholderia pseudomallei Triggers Altered Inflammatory Profiles in a Whole-Blood Model of Type 2 Diabetes-Melioidosis Comorbidity

ABSTRACT Melioidosis is a potentially fatal disease caused by the bacterium Burkholderia pseudomallei. Type 2 diabetes (T2D) is the most common comorbidity associated with melioidosis. B. pseudomallei isolates from melioidosis patients with T2D are less virulent in animal models than those from patients with melioidosis and no identifiable risk factors. We developed an ex vivo whole-blood assay as a tool for comparison of early inflammatory profiles generated by T2D and nondiabetic (ND) individuals in response to a B. pseudomallei strain of low virulence. Peripheral blood from individuals with T2D, with either poorly controlled glycemia (PC-T2D [n = 6]) or well-controlled glycemia (WC-T2D [n = 8]), and healthy ND (n = 13) individuals was stimulated with B. pseudomallei. Oxidative burst, myeloperoxidase (MPO) release, expression of pathogen recognition receptors (TLR2, TLR4, and CD14), and activation markers (CD11b and HLA-DR) were measured on polymorphonuclear (PMN) leukocytes and monocytes. Concentrations of plasma inflammatory cytokine (interleukin-6 [IL-6], IL-12p70, tumor necrosis factor alpha [TNF-α], monocyte chemoattractant protein 1 [MCP-1], IL-8, IL-1β, and IL-10) were also determined. Following stimulation, oxidative burst and MPO levels were significantly elevated in blood from PC-T2D subjects compared to controls. Differences were also observed in expression of Toll-like receptor 2 (TLR2), CD14, and CD11b on phagocytes from T2D and ND individuals. Levels of IL-12p70, MCP-1, and IL-8 were significantly elevated in blood from PC-T2D subjects compared to ND individuals. Notably, differential inflammatory responses of PC-T2D, WC-T2D, and ND individuals to B. pseudomallei occur independently of bacterial load and confirm the efficacy of this model of T2D-melioidosis comorbidity as a tool for investigation of dysregulated PMN and monocyte responses to B. pseudomallei underlying susceptibility of T2D individuals to melioidosis.

Calcific uremic arteriolopathy on multimodal combination therapy: still unmet goal.

Background. Calcific uremic arteriolopathy (CUA) or calciphylaxis though generally noted for its high mortality, recent case reports have shown promising results using single agent therapies. However, it is not clear whether combination therapeutic agents will improve course of the disease. Objective. To determine clinical outcome in subjects with CUA on multimodal treatment. Methods. All patients with end-stage renal failure (ESRF) at The Townsville Hospital, Australia, from April 1, 2006, to March 31, 2011, with diagnosis of CUA were retrospectively studied. Results. Six subjects with CUA (4 females and 2 males) were on various combination therapeutic agents comprising sodium thiosulphate, hyperbaric oxygen, prednisolone, cinacalcet, and parathyroidectomy in addition to intensified haemodialysis, specialist local wound care, and antibiotics. The wounds failed to heal in 3 patients while 5 of the 6 subjects died; cause of death being sepsis in 3 and myocardial infarction in 2. Conclusion. Prognosis of CUA remains poor in spite of multimodal combination therapy. Further prospective studies on a larger population are needed to verify our findings.

The influence of a long term exercise program on lower limb movement variability and walking performance in patients with peripheral arterial disease.

The purpose of this study was to examine the effects of a 12month exercise program on lower limb movement variability in patients with peripheral arterial disease (PAD). Participants (n=21) with an appropriate history of PAD and intermittent claudication (IC) volunteered for this study and were randomly allocated to either a control group (CPAD-IC) (n=11), which received normal medical therapy and a treatment group (TPAD-IC) (n=10), which received normal medical therapy treatment and a 12month supervised exercise program. All participants underwent 2D joint angular kinematic analysis during normal walking to assess lower limb movement variability and walking speed. Between-group differences were analyzed via mixed measures ANOVA. The 12month supervised exercise program made no significant impact on the lower limb movement variability or walking speed of the TPAD-IC group as determined by either intralimb joint coordination or single joint analysis techniques. Long term supervised exercise programs do not appear to influence the lower limb movement variability of PAD-IC patients.

Use of a standardised diabetic ketoacidosis management protocol improved clinical outcomes

We analysed the clinical outcomes of using a standardised protocol in the management of diabetic ketoacidosis. Of 71 admissions, the protocol group (n=35) had significantly shorter length of hospitalisation, shorter time to normalise bicarbonate, fewer incidence of hypokalaemia and hypoglycaemia compared with the control group (n=36).

Extreme hypertriglyceridemia managed with insulin

Extreme hypertriglyceridemia can lead to acute pancreatitis and rapid lowering of serum triglycerides (TG) is necessary for preventing such life-threatening complications. However, there is no established consensus on the acute management of extreme hypertriglyceridemia. We retrospectively reviewed 10 cases of extreme hypertriglyceridemia with mean serum TG on presentation of 101.5 ± 23.4 mmol/L (8982 ± 2070 mg/dL) managed with insulin. Serum TG decreased by 87 ± 4% in 24 hours in those patients managed with intravenous insulin and fasting and 40 ± 8.4% in those managed with intravenous insulin alone (P = .0003). The clinical course was uncomplicated in all except 1 patient who subsequently developed a pancreatic pseudocyst. Thus, combination of intravenous insulin with fasting appears to be an effective, simple, and safe treatment strategy in immediate management of extreme hypertriglyceridemia.