Targeting feasibility evaluation of magnetic resonance-guided focused ultrasound in the management of osteomyelitis: a virtual treatment planning study in 75 patients.

Purpose: Osteomyelitis is one of the most serious complications linked to diabetes and increases the possibility of limb amputation considerably. There exists an important clinical need to improve management of osteomyelitis, especially for diabetic patients who are more susceptible to failures, relapses and chronicity of multiple bone infections. Magnetic resonance-guided focused ultrasound (MRgFUS) can offer a clinical management option for patients with osteomyelitis by providing a non-surgical and potentially rapid-recovery treatment option. Material and Methods: A retrospective study with patients with confirmed osteomyelitis (n = 75) was performed at evaluating the feasibility to target bone infection sites with a clinically approved MRgFUS device (Sonalleve, Profound Medical, Mississauga, ON, Canada). The developed methodology allows using preexisting diagnostic magnetic resonance imaging (MRI) or computed tomography (CT) scans to evaluate the treatment feasibility directly using a MRgFUS treatment planning software. Results: 74.7% of the cases included in our study passed the targetability criteria. Cases were deemed non-targetable if the target was less than 1 cm from the skin or close to a neuro-vascular bundle, metallic implants, or in the way of a defect in the overlying skin. For cases that passed the targetability criteria, an average among patients of 92.7 ± 5.2% of the gross treatment volume could be reached using treatment cells available at the Sonalleve system. Conclusion: The retrospective study presented here is the first step to demonstrate the feasibility of utilizing MRgFUS for the thermal treatment of osteomyelitis.

Progression From Perianal High-Grade Anal Intraepithelial Neoplasia to Anal Cancer in HIV-Positive Men Who Have Sex With Men.

BACKGROUND: High-grade intraepithelial neoplasia is known to progress to invasive squamous-cell carcinoma of the anus. There are limited reports on the rate of progression from high-grade intraepithelial neoplasia to anal cancer in HIV-positive men who have sex with men. OBJECTIVES: The purpose of this study was to describe in HIV-positive men who have sex with men with perianal high-grade intraepithelial neoplasia the rate of progression to anal cancer and the factors associated with that progression. DESIGN: This was a prospective cohort study. SETTINGS: The study was conducted at an outpatient clinic at a tertiary care center in Toronto. PATIENTS: Thirty-eight patients with perianal high-grade anal intraepithelial neoplasia were identified among 550 HIV-positive men who have sex with men. INTERVENTION: All of the patients had high-resolution anoscopy for symptoms, screening, or surveillance with follow-up monitoring/treatment. MAIN OUTCOME MEASURES: We measured the incidence of anal cancer per 100 person-years of follow-up. RESULTS: Seven (of 38) patients (18.4%) with perianal high-grade intraepithelial neoplasia developed anal cancer. The rate of progression was 6.9 (95% CI, 2.8-14.2) cases of anal cancer per 100 person-years of follow-up. A diagnosis of AIDS, previously treated anal cancer, and loss of integrity of the lesion were associated with progression. Anal bleeding was more than twice as common in patients who progressed to anal cancer. LIMITATIONS: There was the potential for selection bias and patients were offered treatment, which may have affected incidence estimates. CONCLUSIONS: HIV-positive men who have sex with men should be monitored for perianal high-grade intraepithelial neoplasia. Those with high-risk features for the development of anal cancer may need more aggressive therapy.

A modified portfolio diet complements medical management to reduce cardiovascular risk factors in diabetic patients with coronary artery disease.

BACKGROUND & AIMS: Secondary prevention can improve outcomes in high risk patients. This study investigated the magnitude of cardiovascular risk reduction associated with consumption of a modified portfolio diet in parallel with medical management. DESIGN: 30 patients with type II diabetes, 6 weeks post bypass surgery received dietary counseling on a Modified Portfolio Diet (MPD) (low fat, 8 g/1000 kcal viscous fibres, 17 g/1000 kcal soy protein and 22 g/1000 kcal almonds). Lipid profiles, endothelial function and markers of glycemic control, oxidative stress and inflammation were measured at baseline and following two and four weeks of intervention. Seven patients with no diet therapy served as time controls. RESULTS: Consumption of the MPD resulted in a 19% relative reduction in LDL (1.9 ± 0.8 vs 1.6 ± 0.6 mmol/L, p < 0.001) with no change in HDL cholesterol. Homocysteine levels dropped significantly (10.1 ± 2.7 vs 7.9 ± 4 µmol/L, p = 0.006) over the study period. Flow mediated dilatation increased significantly in treated patients (3.8 ± 3.8% to 6.5 ± 3.6%, p = 0.004) while remaining constant in controls (p = 0.6). Endothelial progenitor cells numbers (CD34+, CD 133+ and UEA-1+) increased significantly following MPD consumption (p < 0.02) with no difference in migratory capacity. In contrast, time controls showed no significant changes. CONCLUSION: Dietary intervention in medically managed, high risk patients resulted in important reductions in risk factors. Clinical Trials registry number NCT00462436.

Modulation of endothelial function by Korean red ginseng (Panax ginseng C.A. Meyer) and its components in healthy individuals: a randomized controlled trial.

AIMS: Ginseng root and its derivatives remain atop the most widely used medicinal herbs in cardiovascular disease, despite inadequate substantiation of efficacy. We previously reported the potential of Korean red ginseng (KRG) to affect vascular tone by decreasing arterial wave reflection via an unknown mechanism. Given the preclinical link between ginseng intake and vasoactivity related to nitric oxide (NO) production, we sought to directly evaluate the effects of KRG root and its major root components, on an established noninvasive measure of endothelial function. METHODS: In an acute, randomized, placebo-controlled, double-blind, crossover design, 16 healthy participants (9M:7F, age:30 ± 9y, BMI: 24 kg ±3 kg/m(2) , systolicBP/diastolicBP: 109 ± 11/66 ± 8 mmHg) on four occasions were administered: KRG root (3 g), KRG ginsenosides extract, KRG polysaccharides extract, and cornstarch control. Extracted fractions were delivered at doses bioequivalent to those found in 3 g of KRG. Flow-mediated vasodilatation (FMD) assessment, preceding a brachial blood pressure measurement, was performed at baseline and at 90 and 180 min posttreatment to assess endothelial function. RESULTS: KRG significantly improved FMD posttreatment. Maximal vasodilatation of Δ2.57 ± 2.8% occurred at 180 min compared with control (Δ-0.83 ± 2.7%, P = 0.003 for all comparisons). The ginsenoside extract produced a comparable response (Δ1.75 ± 2.6%), but not the polysaccharide fraction (Δ0.10 ± 2.7%). Brachial blood pressure remained unchanged for all treatments (P = 0.45). CONCLUSIONS: KRG acutely improved endothelial function in healthy individuals, which appears to be attributable to its ginsenoside containing fraction. Our data confirm preclinical data and support the potential for these compounds as targets for therapeutic strategies in disorders involving endothelial dysfunction.

Ten-year absolute fracture risk and hip bone strength in Canadian women with systemic lupus erythematosus.

OBJECTIVE: Women with systemic lupus erythematosus (SLE) are at risk of osteoporosis (OP) and fractures because of SLE or its treatments. We aimed to determine in women with SLE (1) the prevalence of low bone mass (LBM) in those < 50 years of age and OP in those > 50 years of age; (2) the 10-year absolute fracture risk in those > 40 years of age using the Canadian Fracture Risk Assessment Tool (FRAX); (3) bone quality using hip structural analysis (HSA); and (4) the associations between HSA and age, SLE duration, and corticosteroid exposure. METHODS: Women without prior OP fractures were eligible. Bone mineral densities at the hip, spine, and femoral neck were determined using dual-energy x-ray absorptiometry. OP was determined using World Health Organization definitions for participants aged ≥ 50 years (32.8%), and LBM was defined as Z-scores ≤ -2.0 for those aged < 50 years. For those aged ≥ 40 years (63.5%), the 10-year probabilities of a major fracture (FRAX-Major) and hip fracture (FRAX-Hip) were calculated. FRAX-Major ≥ 20% or Hip ≥ 3% was considered high risk. HSA was done in a subgroup (n = 81) of patients. RESULTS: The study group was 271 women. Mean (SD) age was 43.8 (13.1) years and SLE duration was 11.6 (10.4) years. OP was diagnosed in 14.6% and LBM in 8.8%. FRAX-Major ≥ 20% was seen in 9 patients (5.3%), of whom 6 were taking OP medications. FRAX-Hip ≥ 3% occurred in 16 patients (9.4%), of whom 9 were taking OP medications. Buckling ratio at the left hip narrow neck was positively correlated with FRAX-Major, FRAX-Hip, SLE duration, and duration of corticosteroid use. CONCLUSION: LBM is prevalent in women with SLE who are < 50 years of age. FRAX may identify those at higher risk of fractures while HSA can assess bone structure noninvasively.

Cardiovascular risk factors, diet and lifestyle among European, South Asian and Chinese adolescents in Canada.

OBJECTIVE: The authors previously reported that adult South Asian immigrants to Canada have an increased risk of cardiovascular disease (CVD) compared to their European and Chinese counterparts. It is unknown whether these ethnic differences also exist among adolescents, and whether they are related to diet and lifestyle. The objective of the present study was to assess the prevalence of CVD risk factors among apparently healthy adolescents in the three largest ethnic population groups in Canada (European, South Asian and Chinese). METHODS: A cross-sectional study among secondary school students in the Greater Toronto Area was undertaken. A total of 203 adolescents from 62 GTA secondary schools were recruited (48% Europeans, 35% Chinese and 18% South Asians) with a mean age of 17.3±1 years; 72% were female. RESULTS: Similar to adults, South Asian adolescents have increased rates of CVD risk factors compared with their European and Chinese peers, including higher prevalence of low high-density lipoprotein levels (P=0.001), high triglycerides (P=0.006) and high triglyceride/high-density lipoprotein levels (P<0.001), despite no significant differences in dietary intake among the ethnic groups. European adolescents had higher rates of self-reported intensity of physical activity (P=0.002) than their Chinese or South Asian peers. CONCLUSIONS: Similar to adult data, South Asian adolescents have comparably higher rates of CVD risk factors compared with their European or Chinese peers, which could partly be attributed to lower physical activity in South Asian adolescents. Whether the findings in these selected samples of healthy adolescents can be generalized to their respective populations requires further validation.

Thrombovascular events affect quality of life in patients with systemic lupus erythematosus.

OBJECTIVE: To compare health-related quality of life (HRQOL) of patients with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) with and without previous thrombovascular events (TE). METHODS: The Medical Outcomes Study Short-Form 36 (SF-36) was used to assess HRQOL in 5 patient groups: (1) primary APS (PAPS; n = 35); (2) APS associated to SLE (SAPS; n = 37); (3) SLE+TE without persistent positive antiphospholipid antibody (SLE+TE-aPL; n = 75); (4) SLE-TE+aPL (n = 71); and (5) SLE-TE-aPL (n = 608). RESULTS: The data on both mental component summary and physical component summary (PCS) scores showed an impaired quality of life in all patient groups. Patients in the SLE+TE-aPL group had a lower PCS score compared to patients in the SLE-TE+aPL group. CONCLUSION: The combination of SLE and TE has a more negative influence on reported HRQOL, compared to having SLE or APS alone.

Healthcare cost and loss of productivity in a Canadian population of patients with and without lupus nephritis.

OBJECTIVE: To compare the healthcare cost and loss of productivity in patients with systemic lupus erythematosus (SLE) with (LN) and without lupus nephritis (lupus nephritis-negative, LNN). METHOD: Patients were classified into those with active (ALN and ALNN) and inactive disease (ILN and ILNN). Patients reported on visits to healthcare professionals and use of diagnostic tests, medications, assistive devices, alternative treatments, hospital emergency visits, surgical procedures, and hospitalizations as well as loss of productivity in the 4 weeks preceding enrollment. RESULTS: Enrollment was 141 patients, 79 with LN and 62 LNN. Patients with LN were more likely to visit rheumatologists and nephrologists, undergo diagnostic tests, and had higher costs for medications than patients who were LNN. The annual healthcare cost averaged $CAN 12,597 ± 9946 for patients with LN and $10,585 ± 13,149 for patients who were LNN, a difference of $2012 (95% CI -$2075, $6100). Patients with ALN had more diagnostic tests and surgical procedures, contributing to a significantly higher annual direct cost ($14,224 ± 10,265) compared to patients with ILN ($9142 ± 8419) and a difference of $5082 (95% CI $591, $9573). The healthcare cost was not different between patients with ALNN and patients with ILNN. In patients with LN and patients who were LNN, < 50% were employed and on average missed 6.5-9 days of work per month. The loss of productivity was significantly higher for caregivers of patients with LN than caregivers of patients who were LNN. CONCLUSION: Healthcare cost and loss of productivity were similar between patients with LN and patients who were LNN; the loss of productivity for caregivers is higher for patients with LN; and the healthcare cost is greater in ALN than in ILN.

The metabolic syndrome in healthy, multiethnic adolescents in Toronto, Ontario: the use of fasting blood glucose as a simple indicator.

BACKGROUND: The prevalence of the metabolic syndrome (MetS) is increasing worldwide and prevention represents a major challenge. Usually identified in middle age, the MetS has pediatric roots and there are variable incidence rates between ethnic groups. Due to the difficulty of diagnosis, it remains largely undetected in adolescents. OBJECTIVES: To assess the presence of the MetS features in healthy, normal-weight, multiethnic adolescents and to determine whether fasting blood glucose (FBG) could function as a simple indicator of its presence. METHODS: A convenience sample of secondary school students was used in a cross-sectional study. General linear model ANCOVA adjusted for multiple pairwise comparisons by the post hoc Tukey-Kramer test was used to assess differences among the tertiles of FBG. RESULTS: A total of 182 adolescents from 62 Greater Toronto Area secondary schools in Ontario were recruited (44% Caucasian, 34% South Asian and 22% Chinese), with a mean (+/- SD) age of 17.4+/-0.9 years, a mean body mass index of 22.1+/-3.4 kg/m2 and a mean FBG of 4.92+/-0.4 mmol/L. Analysis with general linear model ANCOVA across the tertiles of FBG (3.83 mmol/L to 4.78 mmol/L, 4.79 mmol/L to 5.08 mmol/L, and 5.09 mmol/L to 6.45 mmol/L) showed significant linear increases of body mass index (P<0.005), waist circumference (P<0.001), systolic blood pressure (P<0.001) and diastolic blood pressure (P<0.05) with increasing FBG. Stepwise multiple regression analysis indicated systolic blood pressure (beta=0.0078, partial R2=0.039, P=0.007) and waist circumference (beta=0.0081, partial R2=0.025, P=0.035) were independent predictors of the increased FBG level. CONCLUSIONS: MetS markers were present in a sample of healthy multiethnic adolescents in the Greater Toronto Area. FBG could be used as a simple indicator of the MetS to allow for early detection of the presence of the MetS and the introduction of preventive lifestyle measures. Further studies with larger sample sizes should address the accuracy of FBG for diagnosing the MetS.

Effects of Korean red ginseng (Panax ginseng C.A. Mayer) and its isolated ginsenosides and polysaccharides on arterial stiffness in healthy individuals.

BACKGROUND: Preclinical studies indicate a role of Korean red ginseng (KRG) in the modulation of vascular function; however, clinical evidence is scarce. Therefore, the objective of this study was to investigate the effect of KRG root on peripheral blood pressure (BP) and augmentation index (AI), an emerging method to assess cardiovascular risk beyond conventional BP measurements. Furthermore, in an attempt to elucidate which of the major components of KRG is responsible for these effects, the ginsenoside and polysaccharide fractions isolated from the same KRG root were also investigated. METHODS: The study was designed as an acute randomized, controlled, double blind, crossover trial. A total of 17 healthy fasted individuals (gender: 9 males:8 females, age: 30 +/- 9 years, body mass index: 25 +/- 3 kg/m(2), systolic BP (SBP): 110 +/- 10.1, diastolic BP (DBP): 65 +/- 7 mm Hg) received, on separate occasions, four treatments consisting of: 3 g of either placebo, KRG root, or a KRG root bioequivalent dose of ginsenoside or polysaccharide fractions. BP and AI were measured by applanation tonometry at baseline, 1, 2, and 3 h post-treatment. RESULTS: Compared to placebo, 3 g of KRG significantly lowered radial AI by 4.6% (P = 0.045), whereas the ginsenoside fraction comparably decreased AI by 4.8% (P = 0.057), and no effect was observed with the polysaccharides. There were no differences in BP between treatments. CONCLUSION: Although preliminary, this study is the first to demonstrate that KRG may improve arterial stiffness as measured by AI. In addition, it appears that ginsenosides may be the principal pharmacologically active component of the root, rather than the polysaccharide fraction. This study supports the results seen with KRG in the preclinical studies and warrants further investigation on acute and long-term endothelial parameters.

Variability in physician care practices for glucose treatment in stroke patients.

BACKGROUND: Hyperglycemia is noted in up to 60% of stroke patients. Practice guidelines recommend glucose monitoring following stroke but provide few management recommendations. We examined physician care practices for glucose management in stroke patients. METHODS: Emergency physicians, family physicians, general internists, intensive care specialists and neurologists in Ontario comprised the study population. A mailed, self-administered survey inquired about glucose management practices. Proportions of responses for survey questions were determined. Chi-square analysis was used for comparing physician groups. RESULTS: Surveys were mailed to 2,280 physicians; 26.8% returned surveys. There were 278 respondents who reported providing stroke patient care. For physicians treating glucose in stroke patients, 16.6% targeted glucose 4.0-6.0 mmol/l, 52% targeted 6.1-8.0 mmol/l, 13.6% targeted 8.1-12.0 mmol/l, 0.8% targeted 12.1-15.0 mmol/l, and 7.5% were unsure. Comparing specialties, 32% of intensivists, 17.5% of neurologists, 13% of general internists, 14% of emergency physicians, and 0% of family physicians reported targeting 4.0-6.0 mmol/l (p=0.026). Overall, 44% reported aiming for target glucose within 12 hours and 77% within 24 hours from hospital presentation. Intensive care specialists treated glucose most aggressively, including 20% treating, with insulin infusion, patients with no diabetes and initial glucose 6.0-8.0 mmol/l. Emergency physicians were most conservative when treating glucose in stroke patients. CONCLUSION: There is variability in the aggressiveness of glucose management in stroke patients by different physician specialty groups, reflecting the lack of evidence available to guide hyperglycemia management in this setting. These results highlight an important gap in knowledge and recommendations for stroke patient care that must be addressed to ensure optimal patient outcomes.