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1.
BMJ Mil Health ; 2023 Jun 19.
Article in English | MEDLINE | ID: mdl-37336581

ABSTRACT

Spinal cord stimulators (SCS) and peripheral nerve stimulators (PNS) are increasingly used in the treatment of chronic pain, allowing more patients to resume working and return to activities. Military service members face environmental and occupational hazards that expose them to mechanical and electromagnetic forces, both clinical and industrial, that could potentially alter their function. While there are reports of individual hazards, the risk appears to be nominal based on the large number of devices in use and the limited reported complications with these devices. Since a variety of hazards encountered by military patients have the potential to alter SCS and PNS devices, a brief discussion of each patient's specific exposures and related hazards should occur prior to placement. Overall, these devices have demonstrated safety in hazardous areas and few military patients have contraindications for placement based on these factors alone.

2.
BMJ Mil Health ; 169(4): 335-339, 2023 Aug.
Article in English | MEDLINE | ID: mdl-34625516

ABSTRACT

INTRODUCTION: Transdermal fentanyl is a continuous release opioid delivery system intended for use in opioid-tolerant patients requiring around-the-clock opioid therapy. The purpose of this study is to identify the most common indications for transdermal fentanyl prescriptions in active duty US military personnel, and determine whether these prescriptions meet US Food and Drug Administration (FDA) labelling. METHODS: Active duty US military personnel initiating transdermal fentanyl therapy with prescriptions filled at Military Health System pharmacies between 2015 and 2019 were identified in the Military Data Repository. Electronic health records were searched for patient demographic information, clinical information and prescription data. A total of 225 patients with complete data were identified. RESULTS: The most common reason for transdermal fentanyl initiation was chronic non-cancer musculoskeletal pain. Among patients with non-cancer pain, 36% received their initial prescription from an internal medicine/primary care provider, and 35% did not meet published US FDA criteria for opioid tolerance prior to treatment initiation. There was an 81% decrease in patients initiating therapy between 2015 and 2019. CONCLUSIONS: While a substantial minority of transdermal fentanyl prescriptions to US military personnel did not meet FDA guidelines on appropriate use, the overall number of prescriptions fell dramatically over the study period. This suggests that automated profile review or additional targeted policies to limit transdermal fentanyl prescribing are unnecessary at this time.


Subject(s)
Chronic Pain , Military Personnel , Humans , Fentanyl/therapeutic use , Fentanyl/adverse effects , Analgesics, Opioid/therapeutic use , Analgesics, Opioid/adverse effects , Drug Tolerance
3.
BMJ Mil Health ; 169(4): 307-309, 2023 Aug.
Article in English | MEDLINE | ID: mdl-34266972

ABSTRACT

INTRODUCTION: Plane blocks are an increasingly common type of regional anaesthesia technique in the perioperative period. Increased spread of local anaesthesia during plane blocks is thought to be related to an increased area of pain coverage. This study sought to assess differences in injectate spread comparing Tuohy needles with standard insulated stimulating block needles. METHODS: 10 Yorkshire-Cross porcine cadavers were used in this study. Immediately following euthanasia, the cadavers underwent bilateral ultrasound-guided transversus abdominis plane (TAP) block injection with radiopaque contrast dye, with one side placed with a 20 g Tuohy needle, and the other side with a 20 g insulated stimulating block needle. Injectate spread was assessed using plain film X-ray and area of spread was measured to compare differences. RESULTS: All 10 animals underwent successful ultrasound-guided TAP block placement. In all 10 animals, the area of contrast spread was greater with the Tuohy than stimulating needle. Wilcoxon signed-rank test was used to analyse the difference between the groups. The average difference between the two sides was 33.02% (p=0.002). CONCLUSIONS: This is the first study to demonstrate differences in injectate spread with different needle types. This suggests enhanced spread with Tuohy needle compared with standard block needle, and may encourage its use during plane blocks.


Subject(s)
Needles , Nerve Block , Animals , Cadaver , Nerve Block/methods , Swine , Ultrasonography
5.
J Econ Interact Coord ; : 1-40, 2022 Jan 04.
Article in English | MEDLINE | ID: mdl-35003374

ABSTRACT

This paper uses multivariate Hawkes processes to model the transactions behavior of the US stock market as measured by the 30 Dow Jones Industrial Average individual stocks before, during and after the 36-min May 6, 2010, Flash Crash. The basis for our analysis is the excitation matrix, which describes a complex network of interactions among the stocks. Using high-frequency transactions data, we find strong evidence of self- and asymmetrically cross-induced contagion and the presence of fragmented trading venues. Our findings have implications for stock trading and corresponding risk management strategies as well as stock market microstructure design.

6.
Diabet Med ; 37(10): 1696-1704, 2020 10.
Article in English | MEDLINE | ID: mdl-31994233

ABSTRACT

AIM: To compare perinatal outcomes in women with undiagnosed diabetes with gestational diabetes alone, pre-existing diabetes and women without diabetes, and to identify risk factors which distinguish them from women with gestational diabetes alone. METHODS: This population-based cohort study included administrative data on all women who gave birth in Ontario, Canada, during 2002-2015. Maternal/neonatal outcomes were compared across groups using logistic regression, adjusting for confounders. A nested case control study compared women with undiagnosed type 2 diabetes with women with gestational diabetes alone to determine risk factors that would help identify these women. RESULTS: Among 995 990 women, 68 163 had gestational diabetes (6.8%) and, of those women with gestational diabetes,1772 had undiagnosed type 2 diabetes (2.6%). Those with undiagnosed type 2 diabetes were more likely to be older, from a lower income area, have parity > 3 and BMI ≥ 30 kg/m2 compared with gestational diabetes alone. Infants had a higher risk of perinatal mortality (OR 2.3 [1.6-3.4]), preterm birth (OR 2.6 [2.3-2.9]), congenital anomalies (OR 2.1 [1.7-2.5]), neonatal intensive care unit admission (OR 3.1 [2.8-3.5]) and neonatal hypoglycaemia (OR 406.0 [357-461]), which were similar to women with pre-existing diabetes. The strongest predictive risk factors included early gestational diabetes diagnosis, previous gestational diabetes and chronic hypertension. CONCLUSIONS: Women diagnosed with gestational diabetes who develop diabetes within 1 year postpartum are at higher risk of adverse pregnancy outcomes, including perinatal mortality. This highlights the need for earlier diagnosis, preferably pre-pregnancy, and more aggressive treatment and surveillance of suspected type 2 diabetes during pregnancy.


Subject(s)
Congenital Abnormalities/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Diabetes, Gestational/epidemiology , Perinatal Mortality , Pregnancy in Diabetics/epidemiology , Premature Birth/epidemiology , Undiagnosed Diseases/epidemiology , Adolescent , Adult , Case-Control Studies , Cesarean Section/statistics & numerical data , Cohort Studies , Female , Fetal Macrosomia/epidemiology , Humans , Hyperbilirubinemia, Neonatal/epidemiology , Hypertension, Pregnancy-Induced/epidemiology , Hypoglycemia/epidemiology , Income , Infant, Newborn , Infant, Newborn, Diseases/epidemiology , Intensive Care Units, Neonatal , Logistic Models , Maternal Age , Middle Aged , Obesity, Maternal/epidemiology , Ontario/epidemiology , Parity , Pregnancy , Residence Characteristics , Respiratory Distress Syndrome, Newborn/epidemiology , Shoulder Dystocia/epidemiology , Young Adult
7.
Heliyon ; 4(10): e00836, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30320234

ABSTRACT

BACKGROUND: Lower limb amputation (LLA) is a complication of lower limb atherosclerosis, infection and tissue gangrene. Following ipsilateral LLA, the risk of major amputation of the contralateral limb or of death is unknown. The aim of this study was to determine the incidence of a contralateral major LLA, comparing those with a non-malignant/non-traumatic ipsilateral major vs. ipsilateral minor LLA. METHODS: We used pre-existing linked administrative health databases for the study. Data were provided by the Institute for Clinical Evaluation Sciences (ICES), Toronto, Ontario. This is a retrospective population-based cohort study across Ontario, Canada, 2002-2012. Cause-specific Cox regression models were used to obtain hazard ratios. Cumulative incidence functions were used to calculate the risk of contralateral major LLA and the risk of the competing event death. Individuals who did not survive at least 30 days after their first ipsilateral LLA were excluded since they were ineligible to have a contralateral LLA. RESULTS: 5,816 adults underwent an ipsilateral major and 4,143 an ipsilateral minor LLA. The incidences of contralateral major LLA were 4.8 and 2.2 (adjusted HR 2.41, 95% CI 2.04-2.84) after ipsilateral major and minor LLA, respectively. Incidence of death was 18.9 and 11.4 (adjusted HR 1.22, 95% CI 1.13-1.31) following ipsilateral major and minor LLA, respectively. CONCLUSION: There is high incidence of a contralateral major LLA and even higher risk of death following the ipsilateral LLA. Healthcare professionals should develop strategies for contralateral limb preservation in individuals with existing ipsilateral LLA.

8.
Diabet Med ; 34(11): 1637-1645, 2017 11.
Article in English | MEDLINE | ID: mdl-28779518

ABSTRACT

AIMS: To investigate the relationship between increasing parity and diabetes in a large, population-based cohort, and to examine if this relationship is different among high-risk ethnic groups. METHODS: A population-based, retrospective cohort study was performed in 738 440 women aged 18-50 years, who delivered babies in Ontario between 1 April 2002 and 31 March 2011. Diabetes incidence postpartum was calculated for each parity and ethnic group. A multivariable analysis of the effect of parity and ethnicity on the incidence of diabetes was performed using a Cox proportional hazards model, adjusting for confounders. RESULTS: The diabetes incidence rate per 1000 person-years was 3.69 in women with 1 delivery, 4.12 in women with 3 deliveries and 7.62 in women with ≥5 deliveries. Women with ≥3 deliveries had a higher risk of developing diabetes compared with women with 1 delivery [adjusted hazard ratios 1.06 (95% CI 1.01-1.11) for 3 deliveries, 1.33 (95% CI 1.25-1.43) for 4 deliveries and 1.53 (95% CI 1.41-1.66) for ≥5 deliveries). A similar rise in risk could be seen in Chinese and South-Asian women, with the most influence in Chinese women [hazard ratio 4.59 (95% CI 2.36-8.92) for ≥5 deliveries]. CONCLUSIONS: There was a positive and graded relationship between increasing parity and risk of development of diabetes. The influence of parity was seen in all ethnicities. This association may be partly related to increasing weight gain and retention with increasing parity, or deterioration in ß-cell function. This merits further exploration.


Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Ethnicity/statistics & numerical data , Parity/physiology , Adolescent , Adult , Cohort Studies , Diabetes Mellitus, Type 2/ethnology , Female , Humans , Incidence , Infant, Newborn , Middle Aged , Ontario/epidemiology , Pregnancy , Retrospective Studies , Risk Factors , Young Adult
9.
Diabet Med ; 34(7): 958-965, 2017 07.
Article in English | MEDLINE | ID: mdl-28173630

ABSTRACT

AIM: To assess whether rates of hospital encounters with hypoglycaemia and hyperglycaemia display seasonal variation. METHODS: Time series analyses of the monthly rates of hospital encounters (emergency room visits or inpatient admissions) with hypoglycaemia and hyperglycaemia from 2003 to 2012 using linked healthcare databases in Ontario, Canada. RESULTS: Over the study period, there were 129 887 hypoglycaemia and 79 773 hyperglycaemia encounters. The characteristics of people at the time of their encounters were similar across the seasons in 2008 (median age 68 years for hypoglycaemia encounters and 53 years for hyperglycaemia encounters; 50% female; 90% with diabetes). We observed moderate seasonality in both types of encounters (R2 autoregression coefficient 0.58 for hypoglycaemia; 0.59 for hyperglycaemia). The rate of hypoglycaemia encounters appeared to peak between April and June, when on average, there was an additional 49 encounters per month (0.36 encounters per 100 000 persons per month) compared with the other calendar months (5% increase). The rate of hyperglycaemia encounters appeared to peak in January, when on average, there was an additional 69 encounters per month (0.50 encounters per 100 000 persons per month) compared with the other calendar months (11% increase). CONCLUSIONS: In our region, there is seasonal variation in the rate of hospital encounters with hypoglycaemia and hyperglycaemia. Our findings may help to highlight periods of vulnerability for people, may inform future epidemiological studies and may aid in the appropriate planning of healthcare resources.


Subject(s)
Emergency Service, Hospital , Hospitalization , Hyperglycemia/therapy , Hypoglycemia/therapy , Adolescent , Adult , Aged , Child , Combined Modality Therapy , Diabetes Mellitus, Type 1/physiopathology , Electronic Health Records , Female , Humans , Hyperglycemia/epidemiology , Hyperglycemia/etiology , Hypoglycemia/epidemiology , Hypoglycemia/etiology , Infant , Male , Ontario/epidemiology , Risk , Seasons , State Medicine
10.
Anaesthesia ; 72(2): 270, 2017 02.
Article in English | MEDLINE | ID: mdl-28093745
11.
Diabet Med ; 33(3): 395-403, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26201986

ABSTRACT

AIMS: To estimate the healthcare costs attributable to diabetes in Ontario, Canada using a propensity-matched control design and health administrative data from the perspective of a single-payer healthcare system. METHODS: Incident diabetes cases among adults in Ontario were identified from the Ontario Diabetes Database between 2004 and 2012 and matched 1:3 to control subjects without diabetes identified in health administrative databases on the basis of sociodemographics and propensity score. Using a comprehensive source of administrative databases, direct per-person costs (Canadian dollars 2012) were calculated. A cost analysis was performed to calculate the attributable costs of diabetes; i.e. the difference of costs between patients with diabetes and control subjects without diabetes. RESULTS: The study sample included 699 042 incident diabetes cases. The costs attributable to diabetes were greatest in the year after diagnosis [C$3,785 (95% CI 3708, 3862) per person for women and C$3,826 (95% CI 3751, 3901) for men], increasing substantially for older age groups and patients who died during follow-up. After accounting for baseline comorbidities, attributable costs were primarily incurred through inpatient acute hospitalizations, physician visits and prescription medications and assistive devices. CONCLUSIONS: The excess healthcare costs attributable to diabetes are substantial and pose a significant clinical and public health challenge. This burden is an important consideration for decision-makers, particularly given increasing concern over the sustainability of the healthcare system, aging population structure and increasing prevalence of diabetic risk factors, such as obesity.


Subject(s)
Diabetes Mellitus, Type 2/economics , Diabetes Mellitus, Type 2/epidemiology , Health Care Costs/statistics & numerical data , Adult , Aged , Aged, 80 and over , Canada/epidemiology , Case-Control Studies , Cohort Studies , Female , Humans , Male , Middle Aged , Ontario/epidemiology , Prevalence , Young Adult
12.
Diabet Med ; 33(1): 111-8, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25981183

ABSTRACT

AIMS: To examine whether early endocrinologist care reduces the risk of cardiovascular complications among newly diagnosed patients with diabetes of differing complexity. METHODS: We conducted a population-based propensity score-matched cohort study using provincial health data from Ontario, Canada. Adults (≥ 30 years) diagnosed with diabetes between 1 April 1998 and 31 March 2006 who received endocrinologist care in the first year of diagnosis were matched to a comparison group receiving primary care alone (N = 79 020) based on propensity scores and medical complexity (assigned using information on chronic conditions). Individuals were followed for 3- and 5-year outcomes, including non-fatal acute myocardial infarction or coronary heart disease death (primary endpoint), major cardiovascular events (acute myocardial infarction, stroke) or all-cause death, amputation and end-stage renal disease. RESULTS: Among medically complex patients, early endocrinologist care was associated with a lower 3-year incidence of the primary endpoint (hazard ratio 0.89, 95% CI 0.78-1.01) and major cardiovascular events or all-cause death (hazard ratio 0.91, 95% CI 0.85-0.97). These effects persisted after accounting for a higher incidence of end-stage renal disease on follow-up and were greatest in those with ≥ 3 visits to an endocrinologist (primary endpoint: hazard ratio 0.69, 95% CI 0.56-0.86 and 0.61, 95% CI 0.45-0.82, for unadjusted and end-stage renal disease adjusted analyses, respectively). In contrast, no benefit was observed in the non-medically complex subgroup. Overall effects were similar at 5 years. CONCLUSIONS: Early endocrinologist care is associated with a lower incidence of cardiovascular events and death among newly diagnosed patients with diabetes who have comorbid medical conditions.


Subject(s)
Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 2/therapy , Diabetic Angiopathies/prevention & control , Diabetic Cardiomyopathies/prevention & control , Endocrinology/methods , Evidence-Based Medicine , Specialization , Adult , Cardiovascular Diseases/complications , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/mortality , Cohort Studies , Data Anonymization , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/mortality , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/mortality , Diabetic Cardiomyopathies/epidemiology , Diabetic Cardiomyopathies/mortality , Endocrinology/trends , Female , Follow-Up Studies , Humans , Incidence , Information Storage and Retrieval , Male , Mortality , Ontario/epidemiology , Propensity Score , Risk Factors , Single-Payer System , Survival Analysis , Workforce
13.
Can Commun Dis Rep ; 42(10): 205-206, 2016 Oct 06.
Article in English | MEDLINE | ID: mdl-29769982
14.
Diabet Med ; 31(11): 1410-7, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24863747

ABSTRACT

AIMS: To assess the combined impact of socio-economic status and gender on the risk of diabetes-related lower extremity amputation within a universal healthcare system. METHODS: We conducted a population-based cohort study using administrative health databases from Ontario, Canada. Adults with pre-existing or newly diagnosed diabetes (N = 606 494) were included and the incidence of lower extremity amputation was assessed for the period 1 April 2002 to 31 March 2009. Socio-economic status was based on neighbourhood-level income groups, assigned to individuals using the Canadian Census and their postal code of residence. RESULTS: Low socio-economic status was associated with a significantly higher incidence of lower extremity amputation (27.0 vs 19.3 per 10,000 person-years in the lowest (Q1) vs the highest (Q5) socio-economic status quintile. This relationship persisted after adjusting for primary care use, region of residence and comorbidity, and was greater among men (adjusted Q1:Q5 hazard ratio 1.41, 95% CI 1.30-1.54; P < 0.0001 for all male gender-socio-economic status interactions) than women (hazard ratio 1.20, 95% CI 1.06-1.36). Overall, the incidence of lower extremity amputation was higher among men than women (hazard ratio for men vs women: 1.87, 95% CI 1.79-1.96), with the greatest disparity between men in the lowest socio-economic status category and women in the highest (hazard ratio 2.39, 95% CI 2.06-2.77 and hazard ratio 2.30, 95% CI 1.97-2.68, for major and minor amputation, respectively). CONCLUSIONS: Despite universal access to hospital and physician care, we found marked socio-economic status and gender disparities in the risk of lower extremity amputation among patients with diabetes. Men living in low-income neighbourhoods were at greatest risk.


Subject(s)
Amputation, Surgical , Diabetic Foot/surgery , Adult , Amputation, Surgical/economics , Cohort Studies , Diabetic Foot/economics , Diabetic Foot/epidemiology , Diabetic Foot/physiopathology , Female , Follow-Up Studies , Health Status Disparities , Humans , Incidence , Insurance Coverage , Insurance, Health, Reimbursement , Male , Ontario/epidemiology , Poverty Areas , Proportional Hazards Models , Registries , Risk Factors , Severity of Illness Index , Sex Factors , State Medicine
15.
Diabet Med ; 31(7): 806-12, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24588332

ABSTRACT

AIMS: There is evidence to suggest that mammography rates are decreased in women with diabetes and in women of lower socio-economic status. Given the strong association between low socio-economic status and diabetes, we explored the extent to which differences in socio-economic status explain lower mammography rates in women with diabetes. METHODS: A population-based retrospective cohort study in Ontario, Canada, of women aged 50 to 69 years with diabetes between 1999 and 2010 age matched 1:2 to women without diabetes. Main outcome measure is the likelihood of at least one screening mammogram in women with diabetes within a 36-month period, starting as of either 1 January 1999, their 50th birthday, or 2 years after diabetes diagnosis--whichever came last. Outcomes were compared with those in women without diabetes during the same period as their matched counterparts, adjusting for socio-economic status based on neighbourhood income and other demographic and clinical variables. RESULTS: Of 504,288 women studied (188,759 with diabetes, 315,529 with no diabetes), 63.8% had a screening mammogram. Women with diabetes were significantly less likely to have a mammogram after adjustment for socio-economic status and other factors (odds ratio 0.79, 95% CI 0.78-0.80). Diabetes was associated with lower mammogram use even in women from the highest socio-economic status quintile (odds ratio 0.79, 95% CI 0.75-0.83). CONCLUSIONS: The presence of diabetes was an independent barrier to breast cancer screening, which was not explained by differences in socio-economic status. Interventions that target patient, provider, and health system factors are needed to improve cancer screening in this population.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/epidemiology , Diabetes Mellitus/epidemiology , Early Detection of Cancer/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Mammography/statistics & numerical data , Mass Screening/statistics & numerical data , Aged , Breast Neoplasms/economics , Cohort Studies , Diabetes Mellitus/economics , Early Detection of Cancer/economics , Female , Follow-Up Studies , Health Services Accessibility/economics , Health Status Disparities , Humans , Mammography/economics , Mass Screening/economics , Middle Aged , Odds Ratio , Ontario/epidemiology , Retrospective Studies , Socioeconomic Factors
17.
Diabetologia ; 56(12): 2601-8, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24114114

ABSTRACT

AIMS/HYPOTHESIS: The aim of this study was to determine the contemporary rate ratio of mortality and changes over time in individuals with vs without diabetes. METHODS: Annual age- and sex-adjusted mortality rates were compared for adults (>20 years) with and without diabetes in Ontario, Canada, and the UK from January 1996 to December 2009 using The Health Improvement Network (THIN) and Ontario databases. The total number of individuals evaluated increased from 8,757,772 in 1996 to 12,696,305 in 2009. RESULTS: The excess risk of mortality for individuals with diabetes in both cohorts was significantly lower during later vs earlier years of the follow-up period (1996-2009). In Ontario the diabetes mortality rate ratio decreased from 1.90 (95% CI 1.86, 1.94) in 1996 to 1.51 (1.48, 1.54) in 2009, and in THIN from 2.14 (1.97, 2.32) to 1.65 (1.57, 1.72), respectively. In Ontario and THIN, the mortality rate ratios among diabetic patients in 2009 were 1.67 (1.61, 1.72) and 1.81 (1.68, 1.94) for those aged 65-74 years and 1.11 (1.10, 1.13) and 1.19 (1.14, 1.24) for those aged over 74 years, respectively. Corresponding rate ratios in Ontario and THIN were 2.45 (2.36, 2.54) and 2.64 (2.39, 2.89) for individuals aged 45-64 years, and 4.89 (4.35, 5.45) and 5.18 (3.73, 6.69) for those aged 20-44 years. CONCLUSIONS/INTERPRETATION: The excess risk of mortality in individuals with vs without diabetes has decreased over time in both Canada and the UK. This may be in part due to earlier detection and higher prevalence of early diabetes, as well as to improvements in diabetes care.


Subject(s)
Comorbidity , Diabetes Mellitus/mortality , Adult , Age Distribution , Age of Onset , Aged , Canada/epidemiology , Cross-Sectional Studies , Early Diagnosis , Female , Humans , Male , Middle Aged , Ontario/epidemiology , Population Surveillance , Prevalence , Sex Distribution , Survival Rate/trends , United Kingdom/epidemiology
18.
J Pharmacol Exp Ther ; 338(3): 732-40, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21610141

ABSTRACT

Corticosteroids partially suppress cytokine production by chronic obstructive pulmonary disease (COPD) alveolar macrophages. p38 mitogen-activated protein kinase (MAPK) inhibitors are a novel class of anti-inflammatory drug. We have studied the effects of combined treatment with a corticosteroid and a p38 MAPK inhibitor on cytokine production by COPD alveolar macrophages, with the aim of investigating dose-sparing and efficacy-enhancing effects. Alveolar macrophages from 10 patients with COPD, six smokers, and six nonsmokers were stimulated with lipopolysaccharide (LPS) after preincubation with five concentrations of dexamethasone alone, five concentrations of the p38 MAPK inhibitor 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3(4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl)urea (BIRB-796) alone, and all combinations of these concentrations. After 24 h, the supernatants were analyzed for interleukin (IL)-8, IL-6, tumor necrosis factor α (TNFα), granulocyte macrophage-colony-stimulating factor (GM-CSF), IL-1α, IL-1ß, IL-1ra, IL-10, monocyte chemoattractant protein 3, macrophage-derived chemokine (MDC), and regulated on activation normal T cell expressed and secreted (RANTES). The effect of dexamethasone on p38 MAPK activation was analyzed by Western blotting. Dexamethasone and BIRB-796 both reduced LPS-induced cytokine production in a dose-dependent manner in all subject groups, with no differences between groups. Increasing the concentration of BIRB-796 in combination with dexamethasone produced progressively greater inhibition of cytokine production than dexamethasone alone. There were significant efficacy-enhancing benefits and synergistic dose-sparing effects (p < 0.05) for the combination treatment for IL-8, IL-6, TNFα, GM-CSF, IL-1ra, IL-10, MDC, and RANTES in one or more subject groups. Dexamethasone had no effect on LPS-induced p38 MAPK activation. We conclude that p38 MAPK activation in alveolar macrophages is corticosteroid-insensitive. Combining a p38 MAPK inhibitor with a corticosteroid synergistically enhances the anti-inflammatory effects on LPS-mediated cytokine production by alveolar macrophages from patients with COPD and controls.


Subject(s)
Adrenal Cortex Hormones/pharmacology , Anti-Inflammatory Agents/pharmacology , Dexamethasone/pharmacology , Macrophages, Alveolar/metabolism , Naphthalenes/pharmacology , Protein Kinase Inhibitors/pharmacology , Pulmonary Disease, Chronic Obstructive/metabolism , Pyrazoles/pharmacology , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , Adult , Aged , Blotting, Western , Bronchoscopy , Cells, Cultured , Chemokines/biosynthesis , Cytokines/biosynthesis , Dose-Response Relationship, Drug , Drug Synergism , Enzyme-Linked Immunosorbent Assay , Female , HSP27 Heat-Shock Proteins/biosynthesis , Humans , Immunoassay , Lipopolysaccharides/toxicity , Macrophages, Alveolar/drug effects , Male , Middle Aged , Smoking/metabolism , Young Adult
19.
Int J Pediatr Endocrinol ; 2010: 681510, 2010.
Article in English | MEDLINE | ID: mdl-20976257

ABSTRACT

Objective. To assess the impact of exercise consultation on physical activity (PA) levels, anthropometric measures, and metabolic markers in obese adolescents. Methods. Obese adolescents (14-18 years) were randomized to either an exercise consultation (intervention group) or to review "Canada's Physical Activity Guide for Youth" (control group). Outcomes, including accelerometry, anthropometrics, blood pressure, stage of exercise behavior change, fasting glucose, insulin, and lipids, were measured at baseline and 3 months later. Results. Thirty adolescents (mean BMI = 36.1 kg/m(2); SD = 6.9) completed the study. At follow-up, the intervention group had significantly greater PA compared with controls (P < .05). Similarly, the intervention group weighed an average 2.6 kg less than the control group (P < .05), with a mean BMI z-score of 2.15 compared to 2.21 for controls (P = .054). No other differences were noted. Conclusion. Exercise consultation may be a simple approach to increase PA levels, reduce weight, and lower BMI in obese adolescents.

20.
Diabet Med ; 26(5): 510-7, 2009 May.
Article in English | MEDLINE | ID: mdl-19646191

ABSTRACT

AIMS: Although a considerable body of research supports the efficacy of diabetes self-management education (DSME), these programmes are often challenged by high attrition rates. Little is known about factors influencing follow-up use of DSME services, thus the aim of this study was to identify these factors. METHODS: In this multisite prospective analysis, adults with Type 2 diabetes (n = 268) who attended one of two diabetes management centres (DMCs) were followed over a 1-year period from their initial visit. The influence of individual and contextual factors on the number of contacts with DMC providers was examined. Data were analysed within the context of the Health Behavioral Model of Health Services Utilization. RESULTS: In a multivariable negative binomial regression model, the number of contacts over 1 year was greater for those who were female, non-smokers, unemployed, self-referred to the DMC, lived closer to the DMC, had a lower body mass index, or had a longer known duration of diabetes. Follow-up use of services differed significantly between the two sites. Provider contacts were greater at the centre that offered flexible hours of services and a variety of optional educational modules. CONCLUSIONS: Healthcare professionals need to encourage ongoing use of DSME, particularly for individuals prone to lower follow-up use of these services. Providing services that are accessible, convenient, and can easily fit into patients' schedules may increase follow-up use. Further exploration into how operations and delivery of these services influence utilization patterns is strongly recommended.


Subject(s)
Ambulatory Care/statistics & numerical data , Diabetes Mellitus, Type 2/therapy , Patient Acceptance of Health Care/statistics & numerical data , Patient Education as Topic , Adult , Aged , Attitude to Health , Body Mass Index , Female , Humans , Male , Middle Aged , Patient Acceptance of Health Care/psychology , Patient Participation/statistics & numerical data , Prospective Studies , Self Care , Sex Factors , Smoking/epidemiology , Statistics as Topic , Unemployment/statistics & numerical data
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