Does fire drive fatty acid composition in seed coats of physically dormant species?

Seed dormancy is the key driver regulating seed germination, hence is fundamental to the seedling recruitment life-history stage and population persistence. However, despite the importance of physical dormancy (PY) in timing post-fire germination, the mechanism driving dormancy-break within seed coats remains surprisingly unclear. We suggest that seed coat chemistry may play an important role in controlling dormancy in species with PY. In particular, seed coat fatty acids (FAs) are hydrophobic, and have melting points within the range of seed dormancy-breaking temperatures. Furthermore, melting points of saturated FAs increase with increasing carbon chain length. We investigated whether fire could influence seed coat FA profiles and discuss their potential influence on dormancy mechanisms. Seed coat FAs of 25 species within the Faboideae, from fire-prone and fire-free ecosystems, were identified and quantified through GC-MS. Fatty acid profiles were interpreted in the context of species habitat and interspecific variation. Fatty acid compositions were distinct between species from fire-prone and fire-free habitats. Fire-prone species tended to have longer saturated FA chains, a lower ratio of saturated to unsaturated FA, and a slightly higher relative amount of FAs compared to fire-free species. The specific FA composition of seed coats of fire-prone species indicated a potential role of FAs in dormancy mechanisms. Overall, the distinct FA composition between fire-prone and fire-free species suggests that chemistry of the seed coat may be under selection pressure in fire-prone ecosystems.

Endothelial activation is associated with intestinal epithelial injury, systemic inflammation and treatment regimen in children living with vertically acquired HIV-1 infection.

BACKGROUND: Premature development of cardiovascular disease in children living with HIV-1 (CLWH) may be associated with compromised gut barrier function, microbial translocation, immune activation, systemic inflammation and endothelial activation. Biomarkers of these pathways may provide insights into pathogenesis of atherosclerotic disease in CLWH. METHODS: This was a cross-sectional study of CLWH enrolled in the multicentre Early Pediatric Initiation-Canadian Child Cure Cohort (EPIC4 ) who were on antiretroviral therapy (ART) with undetectable viral load. Plasma biomarkers of intestinal epithelial injury [intestinal fatty acid binding protein-1 (IFABP)], systemic inflammation [tumour necrosis factor (TNF) and interleukin-6 (IL-6)] and endothelial activation [angiopoietin-2 (Ang2), soluble vascular endothelial growth factor-1 (sVEGFR1) and soluble endoglin (sEng)] were quantified by enzyme-linked immunosorbent assay. Correlation and factor analysis of biomarkers were used to examine associations between innate immune pathways. RESULTS: Among 90 CLWH, 16% of Ang2, 15% of sVEGFR1 and 23% of sEng levels were elevated relative to healthy historic controls. Pairwise rank correlations between the three markers of endothelial activation were statistically significant (ρ = 0.69, ρ = 0.61 and ρ = 0.65, P < 0.001 for all correlations). An endothelial activation index, derived by factor analysis of the three endothelial biomarkers, was correlated with TNF (ρ = 0.47, P < 0.001), IL-6 (ρ = 0.60, P < 0.001) and intestinal fatty acid binding protein-1 (ρ = 0.67, P < 0.001). Current or past treatment with ritonavir-boosted lopinavir (LPV/r) was associated with endothelial activation (odds ratio = 5.0, 95% CI: 1.7-17, P = 0.0020). CONCLUSIONS: Endothelial activation is prevalent in CLWH despite viral suppression with combination ART and is associated with intestinal epithelial injury, systemic inflammation and treatment with LPV/r.

Rate of dyslipidemia higher among women living with HIV: A comparison of metabolic and cardiovascular health in a cohort to study aging in HIV.

OBJECTIVES: Combination antiretroviral therapy has largely restored the lifespan of persons living with HIV. Data suggest early comorbidities of aging in this population. Past studies focused on men; limited data exist regarding the prevalence of dyslipidaemia in women living with HIV (WLWH). We investigated the prevalence of cardiometabolic abnormalities among WLWH and HIV-negative women in the Children and Women: Antiretrovirals and Markers of Aging (CARMA) cohort, and their relationships to cellular aging markers. METHODS: We conducted a cross-sectional analysis of nonpregnant female patients (156 WLWH and 133 HIV-negative controls, aged 12-69 years) enrolled in CARMA between 2013 and 2017. The Framingham risk score (FRS) and the prevalences of hypertension, diabetes, metabolic syndrome and dyslipideamia were determined using self-report, anthropometrics, chart review and laboratory data. Cellular aging was determined by assessing leukocyte telomere length and blood mitochondrial DNA content. Diagnoses were based on current Canadian guidelines and definitions. RESULTS: HIV-infected status was associated with dyslipidaemia [odds ratio (OR) 2.89; 95% confidence interval (CI) 1.69-5.01], but not diabetes, higher FRS, hypertension or metabolic syndrome. The median age was 43.5 [interquartile range (IQR) 36.8-50.9] years in WLWH and 46.2 (IQR 30.3-54.9) years in HIV-negative controls. WLWH were less likely to be menopausal or use alcohol, and more often had hepatitis C virus infection or a current or past smoking history. Lower mitochondrial DNA content was associated with metabolic syndrome; no other associations were noted between cardiometabolic abnormalities and markers of cellular aging. CONCLUSIONS: Despite their relatively young age, almost two-thirds of WLWH had dyslipidaemia, a significantly greater proportion than in controls. Strategies to address dyslipidaemia and decrease smoking rates may improve long-term outcomes among WLWH.

Congenital anomalies following antenatal exposure to dolutegravir: a Canadian surveillance study.

OBJECTIVE: Dolutegravir is recommended worldwide as a first-line antiretroviral therapy (ART) for individuals living with HIV. A recent study reported increased rates of neural tube defects in infants of dolutegravir-treated women. This study examined rates of congenital anomalies in infants born to women living with HIV (WLWH) in Canada. DESIGN: The Canadian Perinatal HIV Surveillance Programme captures surveillance data on pregnant WLWH and their babies and was analysed to examine the incidence of congenital anomalies. SETTING: Paediatric HIV clinics. POPULATION: Live-born infants born in Canada to WLWH between 2007 and 2017. METHODS: Data on mother-infant pairs, including maternal ART use at conception and during pregnancy, are collected by participating sites. MAIN OUTCOME MEASURES: Congenital anomalies. RESULTS: Of the 2423 WLWH, 85 (3.5%, 95% CI 2.85-4.36%) had non-chromosomal congenital anomalies. There was no evidence of a significant difference in rates of congenital anomalies between women who were on ART in their first trimester (3.9%, CI 1.7-7.6%) or later in the pregnancy (3.9%, 95% CI 2.6-5.6%). Four of the 80 (5.0%, 95% CI 1.4-12.3%) neonates born to WLWH on dolutegravir during the first trimester had congenital anomalies, none were neural tube defects (95% CI 0.00-3.10%). CONCLUSION: Despite recent evidence raising a safety concern, this analysis found no signal for increased congenital anomalies. TWEETABLE ABSTRACT: Five percent of the infants of Canadian women living with HIV on dolutegravir at conception had congenital anomalies; none had neural tube defects.

Summary of the NACI Update on Immunization in Pregnancy with Tetanus Toxoid, Reduced Diphtheria Toxoid and Reduced Acellular Pertussis (Tdap) Vaccine.

BACKGROUND: In Canada, pertussis is an endemic and cyclical disease, with peaks occurring at two- to five-year intervals. Although pertussis incidence varies by age group, unvaccinated or undervaccinated infants are at greatest risk of infection and associated complications. Since the last National Advisory Committee on Immunization (NACI) recommendations published in 2014, new evidence on the safety and effectiveness of tetanus toxoid, reduced diphtheria toxoid and reduced acellular pertussis (Tdap) vaccine administration in pregnancy has become available. OBJECTIVE: To provide guidance on maternal immunization in pregnancy as a strategy to reduce disease incidence and severe outcomes (defined as hospitalization or death) from pertussis infection in infants less than 12 months of age. METHODS: The NACI reviewed evidence on the burden of disease in Canada, vaccine safety and immunogenicity and vaccine effectiveness in jurisdictions that have implemented maternal immunization programs. A total of 59 articles were identified, retrieved and included in the literature review to inform this statement. RESULTS: In the majority of reviewed studies, post immunization increases in antibody levels resulted in more than 90% of women achieving anti-PT levels greater than or equal to 10 IU/ml one month following immunization. In infants, maternal immunization was found to result in increased pertussis antibody concentrations. In the majority of studies, following the receipt of the fourth diphtheria, tetanus and pertussis (DTaP) dose after 15 months of age, no statistically significant differences in antibody levels and avidity were observed between infants whose mothers received Tdap in pregnancy and those whose mothers did not receive Tdap in pregnancy. No major maternal or infant safety issues, including pregnancy outcomes, were reported in the reviewed literature. Effectiveness of maternal Tdap immunization in pregnancy was estimated to be over 90% against pertussis in infants younger than two months of age, with no deaths observed among infants whose mothers received Tdap prior to 36 weeks of pregnancy. Maternal immunization with Tdap in pregnancy also resulted in a reduction in infant disease severity and hospitalization. Vaccine effectiveness was also reported to persist after the receipt of the first three DTaP doses, with immunization in pregnancy resulting in additional protection of up to 70% in children whose mothers received Tdap in pregnancy. CONCLUSION: There is now strong evidence to support the NACI recommendation that immunization with Tdap vaccine should be offered in every pregnancy. This is ideally administered between 27 and 32 weeks of gestation but evidence also supports providing maternal Tdap over a wider range of gestational ages, from 13 weeks up to the time of delivery, in view of programmatic and unique patient considerations.

Summary of the Statement on International Travellers Who Intend to Visit Friends and Relatives.

BACKGROUND: Travellers intending to visit friends and relatives (VFRs) are a specific group of travellers who have been identified as having an increased risk of travel-related morbidity. OBJECTIVE: To provide recommendations for risk reduction in international VFRs. METHODS: Recommendations regarding VFRs were developed based on available travel medicine literature and CATMAT expert opinion. Specific travel-related risks, including infectious disease epidemiology and burden in this population, were reviewed and recommendations were provided to attempt to mitigate these risks. Previous CATMAT statements related to VFRs were referred to and reiterated. RECOMMENDATIONS: Rates of travel-related illness in VFRs tend to be higher for many conditions. Disease-specific risk factors and recommendations are discussed throughout this Statement. CATMAT recommends that VFRs' vaccinations be up-to-date and they be counselled on the importance of various risk reduction activities such as the use of malaria prophylaxis, safe sex practices and injury prevention. Pre- and/or post-travel tuberculosis testing is indicated in certain situations. CONCLUSION: The pre-travel health assessment is an important opportunity to address with VFRs issues regarding health beliefs, health behaviours, current health status and the possibility of pre-existing conditions. Discussions addressing the importance of adherence to health advice and potential challenges to achieving adherence may be necessary.

Summary of recommendations on malaria issues in special hosts.

BACKGROUND: On behalf of the Public Health Agency of Canada, the Committee to Advise on Tropical Medicine and Travel (CATMAT) developed the Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers for Canadian health care providers who are preparing patients for travel to malaria-endemic areas and treating travellers who have returned ill. OBJECTIVE: To provide guidelines on malaria issues related to special hosts. METHODS: CATMAT reviewed all major sources of information on malaria prevention, as well as recent research and national and international epidemiological data, to tailor guidelines to the Canadian context. The evidence-based medicine recommendations were developed with associated rating scales for the strength and quality of the evidence. RECOMMENDATIONS: All people visiting malaria endemic regions should use effective personal protective measures (PPM; topical repellants, bed nets, behavioural choices) and the prescribed chemoprophylaxis. Chemoprophylaxis for pregnant and breastfeeding women and for children requires careful consideration in the context of the pregnancy trimester, the age or size of the infant/child as well as their glucose-6-phosphate dehydrogenase (G6PD) status. Recommendations for long-term travellers, expatriates and people visiting friends and relatives (VFRs) do not differ markedly from those for short-term travellers. Some underlying medical conditions may make individuals more vulnerable to malaria. In addition, some conditions or their treatment may preclude the use of one or more antimalarial medications.

Summary of recommendations for the prevention of malaria by the Committee to Advise on Tropical Medicine and Travel (CATMAT).

BACKGROUND: On behalf of the Public Health Agency of Canada, the Committee to Advise on Tropical Medicine and Travel (CATMAT) developed the Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers for Canadian health care providers who are preparing patients for travel to malaria-endemic areas and treating travellers who have returned ill. OBJECTIVE: To provide guidelines on risk assessment and prevention of malaria. METHODS: CATMAT reviewed all major sources of information on malaria prevention, as well as recent research and national and international epidemiological data, to tailor guidelines to the Canadian context. The evidence-based medicine recommendations were developed with associated rating scales for the strength and quality of the evidence. RECOMMENDATIONS: Used together and correctly, personal protective measures (PPM) and chemoprophylaxis very effectively protect against malaria infection. PPM include protecting accommodation areas from mosquitoes, wearing appropriate clothing, using bed nets pre-treated with insecticide and applying topical insect repellant (containing 20%-30% DEET or 20% icaridin) to exposed skin. Selecting the most appropriate chemoprophylaxis involves assessment of the traveller's itinerary to establish his/her malaria risk profile as well as potential drug resistance issues. Antimalarials available on prescription in Canada include chloroquine (or hydroxychloroquine), atovaquone-proguanil, doxycycline, mefloquine and primaquine.

Summary of recommendations for the diagnosis and treatment of malaria by the Committee to Advise on Tropical Medicine and Travel (CATMAT).

BACKGROUND: On behalf of the Public Health Agency of Canada, the Committee to Advise on Tropical Medicine and Travel (CATMAT) developed the Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers for Canadian health care providers who are preparing patients for travel to malaria-endemic areas and treating travellers who have returned ill. These recommendations aim to achieve appropriate diagnosis and management of malaria, a disease that is still uncommon in Canada. OBJECTIVE: To provide recommendations on the appropriate diagnosis and treatment of malaria. METHODS: CATMAT reviewed all major sources of information on malaria diagnosis and treatment, as well as recent research and national and international epidemiological data, to tailor guidelines to the Canadian context. The evidence-based medicine recommendations were developed with associated rating scales for the strength and quality of the evidence. RECOMMENDATIONS: Malarial management depends on rapid identification of the disease, as well as identification of the malaria species and level of parasitemia. Microscopic identification of blood samples is both rapid and accurate but can be done only by trained laboratory technicians. Rapid diagnostic tests are widely available, are simple to use and do not require specialized laboratory equipment or training; however, they do not provide the level of parasitemia and do require verification. Polymerase chain reaction (PCR), although still limited in availability, is emerging as the gold standard for high sensitivity and specificity in identifying the species.

Drospirenone and non-fatal venous thromboembolism: is there a risk difference by dosage of ethinyl-estradiol?

BACKGROUND: Previous studies concluded that there was an increased risk of non-fatal venous thromboembolism (VTE) with drospirenone. It is unknown whether the risk is differential by ethinyl-estradiol dosage. OBJECTIVES: To assess the risk of VTE with drospirenone and to determine whether drospirenone and ethinyl-estradiol 20 µg (DRSP/EE20) has a lower VTE risk than drospirenone and ethinyl-estradiol 30 µg (DRSP/EE30). METHODS: Our cohort included women aged 18-46 years taking drospirenone or levonorgestrel (LNG)-containing combined oral contraceptives (COCs) in the IMS claims database between 2001 and 2009. VTE was defined using ICD-9-CM coding and anticoagulation. The hazard ratio (HR) from Cox proportional hazards models was used to assess the VTE relative risk (RR) with drospirenone compared with levonorgestrel, adjusted by a propensity score used to control for baseline co-morbidity and stratified by EE dosage and user-type (new/current). RESULTS: The study included 238 683 drospirenone and 193,495 levonorgestrel users. Among new and current users, a 1.90-fold (95% CI, 1.51-2.39) increased VTE relative risk was observed for drospirenone (18.0 VTE/10,000 women-years) vs. levonorgestrel (8.9 VTE/10,000 women-years). In analysis of new users, DRSP/EE20 had a 2.35-fold (95% CI, 1.44-3.82) VTE RR versus LNG/EE20. New users of DRSP/EE30 observed an increased RR versus LNG/EE30 among women starting to use COCs between 2001 and 2006 (2.51, 95% CI, 1.12-5.64) but not between 2007 and 2009 (0.76, 95% CI, 0.42-1.39), attributable to an increased incidence rate with LNG/EE30 from 2007 to 2009. In direct comparison, DRSP/EE20 had an elevated risk of VTE compared with DRSP/EE30 (RR, 1.55; 95% CI, 0.99-2.41). CONCLUSIONS: We observed a modestly elevated risk of VTE with drospirenone, compared with levonorgestrel. The larger VTE incidence rate observed in DRSP/EE20 than in DRSP/EE30 and the increasing VTE incidence rate with levonorgestrel between 2007 and 2009 were unexpected.

Risk of upper gastrointestinal bleeding with oral bisphosphonates and non steroidal anti-inflammatory drugs: a case-control study.

BACKGROUND: Gastrointestinal injuries including gastric ulcers have been reported with oral bisphosphonate therapy. However, the risk of the more serious upper gastrointestinal bleeding (UGB) especially in the community setting with these drugs remains unknown. Similarly, the risk of UGB among users of both bisphosphonates and non steroidal anti-inflammatory drugs (NSAIDs) in the community is also unknown. AIM: To explore the risk of more serious UGB among users of bisphosphonates and the risk of UGB among users of both bisphosphonates and NSAIDs in the community. METHODS: We conducted a case-control study within a cohort of Quebec residents who had received a revascularization procedure from 1995 to 2004. Cohort members were followed up from the date of their first procedure until the earliest of: (1) study outcome, (2) date of death or (3) end of health care coverage. Cases were defined as those with the first diagnosis of a UGB. For each case, 20 controls were selected and matched to the cases by index date, age and cohort entry. Adjusted odds ratios for current use of bisphosphonates, NSAIDs and co-therapy of both drugs were computed. RESULTS: Within the initial cohort, 3253 incident cases of UGBs and corresponding 65 060 matched controls were identified. The adjusted odds ratio (OR) for UGB by current users of bisphosphonates was 1.01 (95% CI, 0.72-1.43). Current NSAID use was associated with an increased risk of UGB OR = 1.75; 95% CI, 1.53-1.99. The OR for use of bisphosphonates and NSAIDs was elevated OR = 2.00; 95% CI, 1.12-3.57. This risk was still elevated for users of bisphosphonates and COX-2 inhibitors [OR = 2.38 (95% CI, 1.26-4.50)]. CONCLUSION: We found no evidence of an increase in the risk of UGB among current users of bisphosphonates. The risk of combined NSAID and bisphosphonate therapy was increased, but this risk was not higher than the risk for NSAID users alone.

A comparison of suicide rates between older adults in Ireland and the UK: 1975-2005.

BACKGROUND: In recent years suicide among older adults has been increasing internationally. The suicide rate among older adults in Ireland is no exception. AIMS: The aim of the current study was to report the rate of suicide among older adults in Ireland and to compare these rates to those of the UK. METHOD: Suicide rates from 1975-2005 for older adults in both Ireland and the UK were obtained and compared. RESULTS: Suicide rates among older adults in Ireland are increasing, while for that same period suicide rates among older adults in the UK are decreasing. CONCLUSIONS: The increased consumption of alcohol in Ireland compared to the UK as well as a higher prevalence of depression among older people in Ireland may account for the observed difference. Findings have implications for suicide prevention in Ireland.

A panel study in congestive heart failure to estimate the short-term effects from personal factors and environmental conditions on oxygen saturation and pulse rate.

OBJECTIVES: Recent studies suggest that persons with congestive heart failure (CHF) may be at higher risk for short-term effects of air pollution. This daily diary panel study in Montreal, Quebec, was carried out to determine whether oxygen saturation and pulse rate were associated with selected personal factors, weather conditions and air pollution. METHODS: Thirty-one subjects with CHF participated in this study in 2002 and 2003. Over a 2-month period, the investigators measured their oxygen saturation, pulse rate, weight and temperature each morning and recorded these and other data in a daily diary. Air pollution and weather conditions were obtained from fixed-site monitoring stations. The study made use of mixed regression models, adjusting for within-subject serial correlation and temporal trends, to determine the association between oxygen saturation and pulse rate and personal and environmental variables. Depending on the model, we accounted for the effects of a variety of personal variables (eg, body temperature, salt consumption) as well as nitrogen dioxide (NO2), ozone, maximum temperature and change in barometric pressure at 8:00 from the previous day. RESULTS: In multivariable analyses, the study found that oxygen saturation was reduced when subjects reported that they were ill, consumed salt, or drank liquids on the previous day and had higher body temperatures on the concurrent day (only the latter was statistically significant). Relative humidity and decreased atmospheric pressure from the previous day were associated with oxygen saturation. In univariate analyses, there was negative associations with concentrations of fine particulates, ozone, and sulphur dioxide (SO2), but only SO2 was significant after adjustment for the effects of weather. For pulse rate, no associations were found for the personal variables and in univariate analyses the study found positive associations with NO(2), fine particulates (aerodynamic diameter of 2.5 microm or under, PM(2.5)), SO2, and maximum temperature, although only the latter two were significant after adjustment for environmental effects. CONCLUSIONS: The findings from the present investigation suggest that personal and environmental conditions affect intermediate physiological parameters that may affect the health of CHF patients.

The coronary risk of cyclo-oxygenase-2 inhibitors in patients with a previous myocardial infarction.

BACKGROUND: Cyclo-oxygenase-2 selective inhibitors have been associated with cardiovascular side effects, but previous studies have generally excluded people with previous myocardial infarction, thereby limiting our knowledge of their cardiotoxicity in this population. OBJECTIVES: To determine whether a history of myocardial infarction modified the risk of acute myocardial infarction associated with the use of various non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: A population-based cohort of 122 079 elderly people with and without previous myocardial infarction newly treated with an NSAID between 1 January 1999 and 30 June 2002 were identified using the computerised health databases of Québec, Canada. A nested-case-control approach was used for the analysis, with controls matched by cohort entry and age. Current users of NSAIDs, those whose last prescription overlapped with the index date, were compared with those who were not exposed to NSAIDs in the year preceding the event. Rate ratios of acute myocardial infarction were estimated using conditional logistic regression and adjusted for potential confounders. RESULTS: Users of rofecoxib, both with and without previous myocardial infarction, were at increased risk of myocardial infarction, with a trend for greater risk among those with a previous event (rate ratio (RR) 1.59, 95% confidence interval (CI) 1.15 to 2.18 v RR 1.23, 95% CI 1.05 to 1.45; p = 0.14 for interaction). By contrast, celecoxib was only associated with an increased risk in people with previous myocardial infarction (RR 1.40, 95% CI 1.06 to 1.84 v RR 1.03, 95% CI 0.88 to 1.20; p = 0.04 for interaction). The available power was insufficient to reliably assess risks among patients with previous myocardial infarction treated with other NSAIDs, dose-response relationships or interaction with aspirin. CONCLUSIONS: Although only rofecoxib use was associated with an increased risk of myocardial infarction in those without a previous event, both rofecoxib and celecoxib were associated with an excess risk of acute myocardial infarction for current users with a history of myocardial infarction. A large randomised trial is required to more completely and reliably assess the cardiovascular safety of celecoxib and traditional NSAIDs in this population of high-risk patients.

Treating the right patient at the right time: access to heart failure care.

Heart failure affects over 500,000 Canadians, and 50,000 new patients are diagnosed each year. The mortality remains staggering, with a five-year age-adjusted rate of 45%. Disease management programs for heart failure patients have been associated with improved outcomes, the use of evidence-based therapies, improved quality of care, and reduced costs, mortality and hospitalizations. Currently, national benchmarks and targets for access to care for cardiovascular procedures or office consultations do not exist. The present paper summarizes the currently available data, particularly focusing on the risk of adverse events as a function of waiting time, as well as on the identification of gaps in existing data on heart failure. Using best evidence and expert consensus, the present article also focuses on timely access to care for acute and chronic heart failure, including timely access to heart failure disease management programs and physician care (heart failure specialists, cardiologists, internists and general practitioners).

ACE-inhibitor use and the long-term risk of renal failure in diabetes.

The incidence of end-stage renal disease (ESRD) owing to diabetes has continued to increase despite the extensive use of angiotensin-converting enzyme (ACE) inhibitors to prevent diabetic nephropathy, primarily from evidence of short-term effectiveness. We assessed the long-term effect of ACE inhibitors on the risk of ESRD. We formed a population-based cohort of all diabetic patients treated with antihypertensive drugs in the Province of Saskatchewan, Canada, between 1982 and 1986. The patients were followed up to the end of 1997 to identify cases of end-stage renal failure. A nested case-control analysis was used with the controls matched to each case on age, diabetes type, and duration of follow-up. The cohort comprised 6102 subjects, of which the 102 cases who developed end-stage renal failure were matched to 4129 controls. Relative to thiazide diuretic use, the adjusted rate ratio of end-stage renal failure associated with the use of ACE inhibitors was 2.5 (95% confidence interval 1.3-4.7), whereas it was 0.8 (95% confidence interval 0.5-1.4) for beta-blockers and 0.7 (95% confidence interval 0.4-1.3) for calcium antagonists. The rate ratio of end-stage renal failure with the use of ACE inhibitors was 0.8 (95% confidence interval 0.3-2.5) during the first 3 years of follow-up, but increased to 4.2 (95% confidence interval 2.0-9.0) after 3 years. ACE-inhibitor use does not appear to decrease the long-term risk of end-stage renal failure in diabetes. Our data suggest instead that ACE inhibitors might actually increase this risk, which may possibly contribute to the continued increasing incidence of ESRD owing to diabetes.

General commentary on access to cardiovascular care in Canada: universal access, but when? Treating the right patient at the right time.

In 2004, the Canadian Cardiovascular Society formed an Access to Care Working Group with a mandate to use the best science and information available to establish reasonable triage categories and safe wait times for common cardiovascular services and procedures through a series of commentaries. The present commentary is the first in the series and lays out issues regarding timely access to care that are common to all cardiovascular services and procedures. The commentary briefly describes the 'right' to timely access, wait lists as a health care system management tool, and the role of the physician as patient advocate and gatekeeper. It also provides advice to funders, administrators and providers who must monitor and manage wait times to improve access to cardiovascular care in Canada and restore the confidence of Canadians in their publicly funded health care system.

Treating the right patient at the right time: access to care in non-ST segment elevation acute coronary syndromes.

In 2004, the Canadian Cardiovascular Society formed an Access to Care Working Group with a mandate to use the best science and information available to establish reasonable triage categories and safe wait times for common cardiovascular services and procedures through a series of commentaries. The present commentary discusses the rationale for access benchmarks for urgent cardiac catheterization and revascularization, including hospital transfer in the setting of non-ST elevation acute coronary syndromes. The literature on standards of care, wait times, wait list management and clinical trials was reviewed. A survey of all cardiac catheterization directors in Canada was performed to develop an inventory of current practices in identifying and triaging patients. The Working Group recommended the following medically acceptable wait times for access to diagnostic catheterization and revascularization in patients presenting with acute coronary syndromes: for diagnostic catheterization and percutaneous coronary intervention, the target should be 24 h to 48 h for high-risk, three to five days for intermediate-risk and five to seven days for low-risk patients; for coronary artery bypass graft surgery, the target should be three to five days for high-risk, two to three weeks for intermediate-risk and six weeks for low-risk patients. All stakeholders must affirm the appropriateness of these standards and work continuously to achieve them. However, some questions remain around what are the best clinical risk markers to delineate the triage categories and the utility of clinical risk scores to assist clinicians in triaging patients for invasive therapies.

Canadian Cardiovascular Society commentary on implantable cardioverter defibrillators in Canada: waiting times and access to care issues.

The Canadian Cardiovascular Society is the national professional society for cardiovascular specialists and researchers in Canada. In the spring of 2004, the Canadian Cardiovascular Society Council formed an Access to Care Working Group in an effort to use the best science and information to establish reasonable triage categories and safe wait times for access to common cardiovascular services and procedures. The Working Group has elected to publish a series of commentaries to initiate a structured national discussion on this very important issue. Access to treatment with implantable cardioverter defibrillators is the subject of the present commentary. The prevalence pool of potentially eligible patients is discussed, along with access barriers, regional disparities and waiting times. A maximum recommended waiting time is proposed and the framework for a solution-oriented approach is presented.