Six cases of silicosis: implications for health surveillance of stonemasons.

BACKGROUND: Silicosis is one of the oldest occupational lung diseases, but it continues to cause significant morbidity and mortality worldwide. AIMS: To report cases of silicosis presenting to two specialist respiratory clinics. METHODS: A retrospective analysis of prospectively collected data of cases of silicosis in workers referred to specialist respiratory clinics. RESULTS: Over the course of 6 years, six cases were identified. The patients were all male with an age range between 24 and 39 years. The duration of silica exposure ranged between 7 and 20 years (mean 13 years). Four cases were entirely asymptomatic at presentation, and two cases described minimal shortness of breath on exertion. Pulmonary function tests were normal in three cases, and a mild restrictive ventilatory defect was documented in the other cases. All had a low apparent predicted probability of pneumoconiosis based on health questionnaires, spirometry and duration of silica exposure. The initial chest X-ray was abnormal in all six cases with radiological evidence of silicosis (International Labour Office profusion category ≥1/1) on imaging, and all had evidence of silicosis on high-resolution computed tomography (HRCT). Three patients had already progressed to progressive massive fibrosis on HRCT scanning at the time of referral to specialist respiratory services. CONCLUSIONS: The appearances of these six cases of silicosis in young, asymptomatic construction workers emphasizes the importance of enforcing effective exposure control and comprehensive surveillance programmes. Our observations highlight the importance of having a low threshold for early radiological screening to promote early and effective detection of this disease.

Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 1: prophylaxis.

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy has been shown to prevent vte; however, unique clinical circumstances in patients with cancer can often complicate the decisions surrounding the administration of prophylactic anticoagulation. No national Canadian guidelines on the prevention of cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin can be used prophylactically in cancer patients at high risk of developing vte. Direct oral anticoagulants are not recommended for vte prophylaxis at this time. Specific clinical scenarios, including renal insufficiency, thrombocytopenia, liver disease, and obesity can warrant modifications in the administration of prophylactic anticoagulant therapy. There is no evidence to support the monitoring of anti-factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, factor Xa levels could be checked at baseline and periodically in patients with renal insufficiency. The use of anticoagulation therapy to prolong survival in cancer patients without the presence of risk factors for vte is not recommended.

Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 2: treatment.

Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy is used to treat vte; however, patients with cancer have unique clinical circumstances that can often make decisions surrounding the administration of therapeutic anticoagulation complicated. No national Canadian guidelines on the management of established cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin is the treatment of choice for cancer patients with established vte. Direct oral anticoagulants are not recommended for the treatment of vte at this time. Specific clinical scenarios, including the presence of an indwelling venous catheter, renal insufficiency, and thrombocytopenia, warrant modifications in the therapeutic administration of anticoagulation therapy. Patients with recurrent vte should receive extended (>3 months) anticoagulant therapy. Incidental vte should generally be treated in the same manner as symptomatic vte. There is no evidence to support the monitoring of anti-factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, levels of anti-factor Xa could be checked at baseline and periodically thereafter in patients with renal insufficiency. Follow-up and education about the signs and symptoms of vte are important components of ongoing patient care.

A comparison of the assessment and management of cardiometabolic risk in patients with and without type 2 diabetes mellitus in Canadian primary care.

AIM: To investigate the cardiometabolic risk (CMR) assessment and management patterns for individuals with and without type 2 diabetes mellitus (T2DM) in Canadian primary care practices. METHODS: Between April 2011 and March 2012, physicians from 9 primary care teams and 88 traditional non-team practices completed a practice assessment on the management of 2461 patients >40 years old with no clinical evidence of cardiovascular disease and diagnosed with at least one of the following risk factor-T2DM, dyslipidaemia or hypertension. RESULTS: There were 1304 individuals with T2DM and 1157 without. Pharmacotherapy to manage hyperglycaemia, dyslipidaemia and hypertension was widely prescribed. Fifty-eight percent of individuals with T2DM had a glycated haemoglobin (HbA1c) ≤7.0%. Amongst individuals with dyslipidaemia, median low-density lipoprotein cholesterol (LDL-C) was 1.8 mmol/l for those with T2DM and 2.8 mmol/l for those without. Amongst individuals with hypertension, 30% of those with T2DM achieved the <130/80 mmHg target, whereas 60% of those without met the <140/90 mmHg target. The composite glycaemic, LDL-C and blood pressure (BP) target outcome was achieved by 12% of individuals with T2DM. Only 17% of individuals with T2DM and 11% without were advised to increase their physical activity. Dietary modifications were recommended to 32 and 10% of those with and without T2DM, respectively. CONCLUSIONS: Patients at elevated CMR were suboptimally managed in the primary care practices surveyed. There was low attainment of recommended therapeutic glycaemic, lipid and BP targets. Advice on healthy lifestyle changes was infrequently dispensed, representing a missed opportunity to educate patients on the long-term benefits of lifestyle modification.

Poor achievement of guidelines-recommended targets in type 2 diabetes: findings from a contemporary prospective cohort study.

AIMS: To prospectively evaluate diabetes management in the primary care setting and explore factors related to guideline-recommended triple target achievement [blood pressure (BP) ≤ 130/80 mmHg, A1C ≤ 7% and low-density lipoprotein (LDL)-cholesterol < 2.5 mmol/l]. METHODS: Baseline, 6 and 12 month data on clinical and laboratory parameters were measured in 3002 patients with type 2 diabetes enrolled as part of a prospective quality enhancement research initiative in Canada. A generalised estimating equation model was fitted to assess variables associated with triple target achievement. RESULTS: At baseline, 54%, 53% and 64% of patients, respectively, had BP, A1C and LDL-cholesterol at target; all three goals were met by 19% of patients. The percentage of individuals achieving these targets significantly increased during the study [60%, 57%, 76% and 26%, respectively, at the final visit, p < 0.0001 except for A1C, p = 0.27]. A much smaller proportion of patients had adequate control during the entire study period [30%, 39%, 53% and 7%, respectively]. In multivariable analysis, women, patients younger than 65 years and patients of Afro-Canadian origin were less likely to achieve the triple target. DISCUSSION: As part of a quality enhancement research initiative, we observed important improvements in the attainment of guidelines-recommended targets in patients with type 2 diabetes followed for a 12-month period in the primary care setting; however, many individuals still failed to achieve and especially maintain optimal goals for therapy, particularly the triple target. Results of the multivariable analysis reinforce the need to address barriers to improve diabetes care, particularly in more susceptible groups.

Mechanisms by which dopamine alters blood flow distribution during lobar collapse in dogs.

Dopamine increases blood flow to a hypoxic left lower lobe in dogs. To elucidate possible mechanisms, left lower lobe collapse was induced in anesthetized dogs, and lobar (QLLL) and total (QT) pulmonary blood flow was measured by electromagnetic flow probes. Dopamine infusion increased mean pulmonary arterial pressure (Ppa), QT, and QLLL. However, the increase in QLLL was double that produced by a similar increase in Ppa without increase in QT (inflation of a Swan-Ganz balloon in right pulmonary artery) or by a similar increase in QT with smaller increase in Ppa (opening of arteriovenous fistulas). QLLL/QT was not changed by opening arteriovenous fistulas, but was increased by Swan-Ganz balloon inflation, and by infusion of dopamine. It is concluded that the increase in QLLL/QT produced by dopamine was due to a decrease in hypoxic vasoconstriction in the lobe secondary to an increase in mixed venous PO2 and to vasoconstriction in the oxygenated lung.

A call to arms: economic barriers to optimal dialysis care.

Epidemic growth rates and the enormous cost of dialysis pressure end-stage renal disease (ESRD) delivery systems around the world. Payers of dialysis services can constrain costs through (1) limiting access to dialysis, (2) reducing the quality of dialysis, and (3) placing constraints on modality distribution. In order to secure the necessary resources for ESRD care, we propose that the nephrology community consider the following suggestions: First, future leaders in dialysis should acquire additional advanced training in innovative pathways such as health care economics, business and health care administration, and health care policy. Second, the international nephrology community must strongly engage in ongoing advocacy for accessible, high quality, cost-effective care.Third, efforts should be made to better define and then implement optimal dialysis modality distributions that maximize patient outcomes but limit unnecessary costs. Fourth, industry should be encouraged to lower the unit cost of dialysis, allowing for improved access to dialysis, especially in developing countries. Fifth, research should be encouraged that seeks to identify measures that will reduce dialysis costs but will not impair quality of care. Finally, early referral of patients with progressive renal disease to nephrology clinics, empowerment of informed patient choice of dialysis modality, and proper and timely access creation should be encouraged and can be expected to help limit overall expenditures. Ongoing efforts in these areas by the nephrology community will be essential if we are to overcome the challenges of ESRD growth in this new decade.

Pharyngeal narrowing in end-stage renal disease: implications for obstructive sleep apnoea.

Sleep apnoea is common in patients with end-stage renal disease (ESRD). It was hypothesised that this is related to a narrower upper airway. Upper airway dimensions in patients with and without ESRD and sleep apnoea were compared, in order to determine whether upper airway changes associated with ESRD could contribute to the development of sleep apnoea. An acoustic reflection technique was used to estimate pharyngeal cross-sectional area. Sleep apnoea was assessed by overnight polysomnography. A total of 44 patients with ESRD receiving conventional haemodialysis and 41 subjects with normal renal function were studied. ESRD and control groups were further categorised by the presence or absence of sleep apnoea (apnoea/hypopnoea index > or =10 events.h(-1)). The pharyngeal area was smaller in patients with ESRD compared with subjects with normal renal function: 3.04 +/- 0.84 versus 3.46 +/- 0.80 cm(2) for the functional residual capacity and 1.99 +/- 0.51 versus 2.14 +/- 0.58 cm(2) for the residual volume. The pharynx is narrower in patients with ESRD than in subjects with normal renal function. In conclusion, since a narrower upper airway predisposes to upper airway occlusion during sleep, it is suggested that this factor contributes to the pathogenesis of sleep apnoea in dialysis-dependent patients.

Interpreting cost-effectiveness in dialysis: can the most expensive be more expensive?

In this issue, Tonelli et al. describe the cost-effectiveness of arteriovenous fistulae (AVF) screening, and conclude that such a program represents "good value for money." Here, I examine the robustness of this conclusion by considering traditional definitions of acceptable cost-effectiveness and more pragmatic definitions, which include consideration of the maximum amount that society would be willing to pay for hemodialysis.

The impact of home nocturnal hemodialysis on end-stage renal disease therapies: a decision analysis.

Home nocturnal hemodialysis (HNHD) is cost-effective relative to in-center hemodialysis (IHD) in short-run analyses. The effect in long-run analyses, when technique failures, declining benefits, delayed training, transplantation and death are considered, is unknown. We used decision analysis techniques to examine the relative cost-effectiveness of HNHD and IHD, projecting future costs and health effects over a lifetime with end-stage renal disease. We developed a Markov state-transition model comparing two strategies: only IHD or starting on IHD and subsequently transferring to HNHD. The model incorporates transplantation. In the base case, half the population was eligible for transplantation, with (1/3) of grafts from live donors. The time to transplant was 0.75 years for live and 5 years for deceased donor transplants. The delay before initiation of HNHD was 5 years. Costs and outcomes were discounted at 3% per annum. Model parameters were derived from a literature review. We also conducted one-way sensitivity analyses and Monte Carlo simulations. The HNHD strategy was associated with a quality-adjusted survival estimate of 5.79 quality-adjusted life years (QALYs), with lifetime costs of $538 094. The values for IHD were 5.31 QALYs and $543 602, respectively. Thus, HNHD is cost saving while improving quality of life. The incremental cost-utility ratio was consistently less than $50 000 per QALY in sensitivity and Monte Carlo analyses. Important determinants of cost-effectiveness were transplantation time and whether benefits declined over time. Our model suggests that HNHD improves quality-adjusted survival over IHD at an economically attractive cost-effectiveness ratio.

CO2 and mechanical factors reduce blood flow in a collapsed lung lobe.

Left lower lobe-to-total blood flow ratio (Ql/QT) was measured with electromagnetic flow probes in anesthetized open-chest dogs. There was a 66% reduction in Ql/QT during lobar collapse, a 53% reduction during lobar ventilation hypoxia with pulmonary venous PO2 and PCO2 equal to mixed venous tensions, and a 45% reduction during a similar degree of ventilation hypoxia but with normal end-tidal PCO2. We concluded that the reduction in blood flow during lobar collapse is due predominantly to hypoxic vasoconstriction, but that this mechanism is augmented by the raised PCO2 and mechanical factors present during collapse.

Effects of dopamine and dobutamine on the distribution of pulmonary blood flow during lobar ventilation hypoxia and lobar collapse in dogs.

Hypoxic pulmonary vasoconstriction was induced in the left lower lobe of fifteen dogs by ventilating the lobe with 7% O2 or by absorption collapse, and the distribution of flow between the lobe and the remainder of the lung was measured with electromagnetic flow probes. The lobar to total blood flow ratio was reduced by lobar ventilation hypoxia and decreased further during lobar collapse. In seven dogs, an infusion of 20 micrograms kg-1 min-1 of dopamine produced an increase in total blood flow, an increase in pulmonary artery pressure (P less than 0.01), and an increase in lobar to total flow ratio (P less than 0.05) during both hypoxic states. There was a significant fall in arterial PO2 (P less than 0.01) during ventilation hypoxia. Similar changes in total and lobar to total flow ratio (P less than 0.01) were observed in eight dogs given 20 micrograms kg-1 min-1 of dobutamine, but there were no changes in pulmonary artery pressure. The greater increase in total flow (+ 111%) resulted in a marked increase in mixed venous PO2 and no significant changes in arterial PO2 in this group of dogs. It is concluded that both drugs produce an increase in lobar to total blood flow ratio and shunt fraction, but that the mechanisms causing the redistribution of flow may differ.