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Biomedical subjects

E Burgess

Publications and source records attributed to E Burgess.

At least 19 recordsLinked to original sources

The Biomolecular Interaction Network Database and related tools 2005 update.

The Biomolecular Interaction Network Database (BIND) (http://bind.ca) archives biomolecular interaction, reaction, complex and pathway information. Our aim is to curate the details about molecular interactions that arise from published experimental research and to provide this information, as well as tools to enable data analysis, freely to researchers worldwide. BIND data are curated into a comprehensive machine-readable archive of computable information and provides users with methods to discover interactions and molecular mechanisms. BIND has worked to develop new methods for visualization that amplify the underlying annotation of genes and proteins to facilitate the study of molecular interaction networks. BIND has maintained an open database policy since its inception in 1999. Data growth has proceeded at a tremendous rate, approaching over 100 000 records. New services provided include a new BIND Query and Submission interface, a Standard Object Access Protocol service and the Small Molecule Interaction Database (http://smid.blueprint.org) that allows users to determine probable small molecule binding sites of new sequences and examine conserved binding residues.

Animals↗

Consent for clinical research in the neonatal intensive care unit: a retrospective survey and a prospective study.

BACKGROUND: Recruitment into research studies in the neonatal intensive care unit has been problematic. Therefore suggestions have been made to take decision making about enrollment out of the hands of the parents. OBJECTIVE: To understand parental perceptions of the process of recruitment and enrollment for research in the neonatal intensive care unit. METHOD: A questionnaire was developed and used in both a retrospective survey and a prospective study of parents whose newborns were enrolled in trials in a neonatal intensive care unit. Closed ended and open ended questions were included, as well as demographic questions. RESULTS: The retrospective survey had a 79% response rate (29 of 38). Overall, 90% of parents felt that they had made informed decisions, and 93% were against the option that a doctor decide if the newborn should be enrolled into a study, rather than the parent. Although some parents (38%) found that recruitment did add "stress to an already stressful situation", 90% felt that they had made informed decisions and understood the elements of the study. Most parents had been requested to enroll their newborn into more than one trial, and, on average, they thought that they would be comfortable with enrollment into two studies (range 0-6). When asked how the process could be improved, parents suggested that information be made available before delivery. The responses of parents in the prospective study were mostly consistent with those from the retrospective survey. CONCLUSIONS: Overall the parents did not support the suggestion that decision making about enrollment be taken away from parents and put into the hands of doctors. The healthcare team should support parents in their role of decision maker, enhance availability of the research staff, and provide more information about the research.

Attitude↗

Oral vitamin B(12) and high-dose folic acid in hemodialysis patients with hyper-homocyst(e)inemia.

BACKGROUND: Hyper-homocyst(e)inemia is an independent risk factor for atherosclerotic vascular disease in patients with end-stage renal disease (ESRD), although optimal treatment remains unknown. This randomized, double-blind, placebo-controlled study was designed to measure the effect of high-dose oral vitamin B(12) and folic acid on predialysis total homocyst(e)ine levels in patients with ESRD. METHODS: We studied 81 hemodialysis patients who had hyper-homocyst(e)inemia (>16 micromol/L) on varied doses of a multivitamin containing 1 mg of folic acid/day. After screening blood work, all patients were switched to daily multivitamin therapy, including 1 mg of folic acid for four weeks. For all patients, vitamin B(12), 1 mg/day, was added for an additional four weeks. Patients were then randomized to receive four weeks of 0, 5, or 20 mg of folic acid in addition to the multivitamin and vitamin B(12) (all given daily). RESULTS: Screening homocyst(e)ine levels (mean 27.7 micromol/L) decreased by 19.2% after four weeks of treatment with a daily multivitamin containing 1 mg of folic acid (P < 0.001). Homocyst(e)ine levels were reduced further from 22.3 to 18.6 micromol/L (mean reduction 16.7%, 95% CI 11.8 to 21.6%, P < 0.001) after four weeks of therapy with vitamin B(12) (1 mg/day). There was no significant difference in mean reduction of homocyst(e)ine levels after therapy with high-dose folic acid compared with placebo (P = 0.35). CONCLUSIONS: The optimal oral treatment of hyper-homocyst(e)inemia in hemodialysis patients consists of 1 mg of folic acid and 1 mg of oral vitamin B(12) daily. Whether this treatment will lower the risk of future atherosclerotic vascular events remains to be investigated.

Administration, Oral↗

Cardiovascular disease in patients with chronic kidney disease: getting to the heart of the matter.

The high prevalence of cardiovascular disease (CVD) in patients with kidney disease is well described. This Canadian, multicenter, observational cohort study reports the prevalence and risk factors of CVD associated with kidney disease, in a cohort of patients with established chronic kidney disease (CKD), who are followed-up by nephrologists. This analysis sought to answer 2 questions: (1) in patients with established CKD, are the prevalence and progression of CVD accounted for by conventional or uremia-related risk factors, and (2) to what extent can progression to renal replacement therapy (RRT) be explained by CVD versus traditional risk factors for kidney disease? This study population consists of 313 patients (predominantly men) who had a mean age of 56 years and a mean creatinine clearance of 36 mL/min. Thirty percent were diabetic. The overall prevalence of CVD was 46%, and was independent of severity of kidney dysfunction (P = 0.700). The median follow-up time was 23 months, for a total of 462 patient years. We note the overall incidence of CVD events (new CVD or worsening of CVD) was 47/244 (20%). The best predictors of new CVD events among those without preexisting CVD were diabetes (odds ratio [OR] = 5.35, P = 0.018) and age (OR = 1.26, P = 0.08). In those with preexisting CVD, low diastolic pressure (DP) (OR =.72, P = 0.004) and high triglycerides (OR = 1.48, P = 0.019) at baseline were independent predictors of progression of CVD. We could not determine an independent impact of kidney function on CVD in the overall cohort. Furthermore, we determined that the presence of CVD itself confers an increased risk for progression to RRT (relative risk [RR] = 1.58, P = 0.047), adjusted for kidney function. This is the first in-depth analysis of CVD in a cohort of patients with established chronic kidney disease who are not on dialysis. The question regarding the impact of the altered biology of uremia in contributing to CVD progression remains unanswered, and clearly needs further study. However, the findings do raise the issue of whether aggressive treatment of CVD and risk factors might, in fact, reduce progression to RRT. Further large-scale, observational studies as well as interventional studies are needed to more clearly understand the complex biology of cardiovascular and kidney disease progression.

Age Distribution↗

Renal effects of angiotensin II receptor antagonists.

Among the many roles that angiotensin II plays in the kidney, one of the most important is the direct and indirect regulation of sodium excretion. Angiotensin II is produced within the kidney, where concentrations appear to be far in excess of those detected in plasma. High levels of angiotensin II subtype 1 receptors have been detected on the luminal side of the tubular cells in the proximal convoluted tubule, and these have been implicated in the regulation of sodium excretion. This portion of the nephron is responsible for the reabsorption of 65% of filtered sodium. It is, therefore, reasonable to assume that blockade of these receptors, using non-peptide angiotensin II receptor antagonists, will bring about an increase in renal excretion of sodium. There is, however, the possibility that, if the effect is small, downstream sites will have the capacity to reabsorb the increased sodium delivered to the distal nephron. Studies in hypertensive animal models have established that angiotensin II subtype 1 receptor antagonists stimulate natriuresis. However, the studies that have been performed to date in humans are deficient in that they have been conducted in normotensive subjects. Also, subjects have only been followed up for 6 or 8 h and thus these studies did not examine whether the observed short-term natriuresis was followed by an enhanced reabsorption of sodium. Another study, designed to overcome the deficiencies of previous studies, has investigated the natriuretic effect of telmisartan in hypertensive patients.

Angiotensin II↗

Self-measurement of blood pressure: accuracy, patient preparation for readings, technique and equipment.

OBJECTIVE: Self-measurement of blood pressure is commonly performed by those persons with hypertension and is advocated in many national hypertension guidelines. We examined accuracy of readings, patient knowledge, and preparation for readings, technique and equipment. DESIGN: The study was a prospective observational design. Sixty-nine hypertensive patients were recruited from a tertiary referral center and by newspaper advertisement. All patients had previously self-measured their blood pressure. The patients initially measured their blood pressure under direct supervision in a clinic using their usual preparation, technique and their own equipment. Then after a five-min rest, blood pressures were measured twice both by research nurse and the patient in an alternating sequence. The nurse used a standardized blood pressure measurement technique. RESULTS: Inadequate patient knowledge and performance of measurement technique and inaccurate equipment was common. The average initial patient systolic reading prior to the five-minute rest was higher than that of the trained nurse (9.1 +/- 13 mmHg systolic, p < 0.001 and 1.5 +/- 8.0 mmHg diastolic, p = 0.12). Almost half (42%) of the initial patient blood pressure readings differed in classification of hypertension/normotension from the nurse. The difference between the patient and nurse readings after the five-min rest was 3.8 +/- 11.8 / 1.1 +/- 6.8 mmHg. CONCLUSIONS: Care must be taken in interpreting patient self-measured blood pressure unless there has been adequate training and assessment of patient and equipment accuracy. Studies of health care professionals reveal similar problems therefore widespread efforts to standardize blood pressure measurement are necessary.

Aged↗

The 2000 Canadian recommendations for the management of hypertension: Part one--therapy.

OBJECTIVE: To provide updated, evidence-based recommendations for the therapy of hypertension in adults. OPTIONS: For patients with hypertension, there are a number of lifestyle manoeuvres and antihypertensive agents that may control blood pressure. Randomized trials evaluating first- line therapy with thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, centrally acting agents or angiotensin II receptor antagonists were reviewed. OUTCOMES: The health outcomes considered were changes in blood pressure, cardiovascular morbidity, and cardiovascular and/or all-cause mortality rates. Economic outcomes were not considered due to insufficient evidence. EVIDENCE: Medline searches were conducted from the period of the last revision of the Canadian Recommendations for the Management of Hypertension (May 1998 to October 2000). Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and mortality. BENEFITS, HARMS, AND COSTS: Various lifestyle manoeuvres and antihypertensive agents reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to all aspects of the therapy of patients with hypertension, including lifestyle modifications proven to lower blood pressure, treatment thresholds, target blood pressures, choice of agents in various settings and strategies to enhance adherence. Lower thresholds for blood pressure treatment are advocated for people with other cardiovascular risk factors or established hypertensive target organ damage. Implicit in the recommendations for therapy is the principle that treatment should be individualized for each patient and the choice of agent should be dictated by coexistent conditions. For the treatment of uncomplicated essential hypertension, thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors or calcium channel blockers may be appropriate, depending on individual circumstances. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Only those recommendations achieving high levels of consensus are reported here. These guidelines will be updated annually.

Adult↗

The 2000 Canadian recommendations for the management of hypertension: part two--diagnosis and assessment of people with high blood pressure.

OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of high blood pressure in adults. OPTIONS: For people with high blood pressure, the assignment of a diagnosis of hypertension depends on the appropriate measurement of blood pressure, the level of the blood pressure elevation, the duration of follow-up and the presence of concomitant vascular risk factors, target organ damage and established atherosclerotic diseases. For people diagnosed with hypertension, defining the overall risk of adverse cardiovascular outcomes requires laboratory testing, a search for target organ damage and an assessment of the modifiable causes of hypertension. Out-of-clinic blood pressure assessment and echocardiography are options for selected patients. OUTCOMES: People at increased risk of adverse cardiovascular outcomes and were identified and quantified. EVIDENCE: Medline searches were conducted from the period of the last revision of the Canadian recommendations for the management of hypertension (May 1998 to October 2000). Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the identification of people at increased risk of cardiovascular morbidity and mortality. BENEFITS, HARMS AND COSTS: The identification of people at higher risk of cardiovascular disease will permit counselling for lifestyle manoeuvres and the introduction of antihypertensive drugs to reduce blood pressure for patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to aspects of the diagnosis and assessment of patients with hypertension, including the accurate measurement of blood pressure, criteria for the diagnosis of hypertension and recommendations for follow-up, routine and optional laboratory testing, assessment for renovascular hypertension, home and ambulatory blood pressure monitoring, and the role of echocardiography in hypertension. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Only the recommendations achieving high levels of consensus are reported here. These guidelines will be updated annually. ENDORSEMENT: These recommendations are endorsed by the Canadian Hypertension Society, The Canadian Coalition for High Blood Pressure Prevention and Control, The College of Family Physicians of Canada, The Heart and Stroke Foundation of Canada, The Adult Disease Division and Bureau of Cardio-Respiratory Diseases and Diabetes at the Centre for Chronic Disease Prevention and Control of Health Canada.

Adrenal Gland Neoplasms↗

Parental presence during anaesthesia induction for outpatient surgery of the infant.

We conducted a randomized controlled trial of parental presence during anaesthesia induction for outpatient surgery in 73 infants (aged 1-12 months). Effects of parental presence on infant and parental outcomes, including anxiety, health care attitudes and satisfaction with the anaesthesia and surgery experience were evaluated. Results demonstrated that parental presence had no impact on infant behavioural distress during induction. In addition, parents who were present demonstrated comparable anxiety levels and health care attitudes before and after surgery, as well as comparable levels of satisfaction with the surgical experience compared to parents who were absent during induction. We discuss reasons for the lack of treatment effects from parental presence, and new directions for future research to identify subgroups of children who may most benefit from the opportunity to have parents involved in the perioperative period.

Ambulatory Surgical Procedures↗

Development of an instrument to investigate parents' perceptions of research with newborn babies.

Neonatal intensive care nurses are often involved in research protocols as investigators, research assistants or staff nurses implementing the protocol and providing support and explanations to families. It is important, therefore, that nurses have information about parents' understanding of and attitudes towards the research process. The purpose of this study was to begin an exploration of parents' perceptions about research with newborn babies through the development and validation of a survey instrument. The questionnaire included: demographic questions; scaled items about research with newborn babies; scenarios describing research studies that varied in degree of risk and benefit to the newborn baby; questions about parents' willingness to enrol their newborn baby in the studies described; and questions regarding circumstances under which consent should be sought. Content and face validity were established by an expert panel and a pilot test conducted with a small group of health care professionals and lay persons. A convenience sample of 231 parents of newborn babies completed the final version of the questionnaire. Factor analysis revealed seven factors corresponding to issues identified in the literature, providing evidence of construct validity. Parents appeared to have no difficulty in completing the instrument and all questions were answered by the majority of participants. It was concluded that the questionnaire had adequate psychometric properties and that a mixed method approach can be fruitful in exploring sensitive issues.

Adult↗

Lifestyle modifications to prevent and control hypertension. 1. Methods and an overview of the Canadian recommendations. Canadian Hypertension Society, Canadian Coalition for High Blood Pressure Prevention and Control, Laboratory Centre for Disease Control at Health Canada, Heart and Stroke Foundation of Canada.

OBJECTIVE: To provide updated, evidence-based recommendations for health care professionals on lifestyle changes to prevent and control hypertension in otherwise healthy adults (except pregnant women). OPTIONS: For people at risk for hypertension, there are a number of lifestyle options that may avert the condition--maintaining a healthy body weight, moderating consumption of alcohol, exercising, reducing sodium intake, altering intake of calcium, magnesium and potassium, and reducing stress. Following these options will maintain or reduce the risk of hypertension. For people who already have hypertension, the options for controlling the condition are lifestyle modification, antihypertensive medications or a combination of these options; with no treatment, these people remain at risk for the complications of hypertension. OUTCOMES: The health outcomes considered were changes in blood pressure and in morbidity and mortality rates. Because of insufficient evidence, no economic outcomes were considered. EVIDENCE: A MEDLINE search was conducted for the period January 1996 to September 1996 for each of the interventions studied. Reference lists were scanned, experts were polled, and the personal files of the authors were used to identify other studies. All relevant articles were reviewed, classified according to study design and graded according to level of evidence. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and premature death caused by untreated hypertension. BENEFITS, HARMS AND COSTS: Lifestyle modification by means of weight loss (or maintenance of healthy body weight), regular exercise and low alcohol consumption will reduce the blood pressure of appropriately selected normotensive and hypertensive people. Sodium restriction and stress management will reduce the blood pressure of appropriately selected hypertensive patients. The side effects of these therapies are few, and the indirect benefits are well known. There are certainly costs associated with lifestyle modification, but they were not measured in the studies reviewed. Supplementing the diet with potassium, calcium and magnesium has not been associated with a clinically important reduction in blood pressure in people consuming a healthy diet. RECOMMENDATIONS: (1) It is recommended that health care professionals determine the body mass index (weight in kilograms/[height in metres]2) and alcohol consumption of all adult patients and assess sodium consumption and stress levels in all hypertensive patients. (2) To reduce blood pressure in the population at large, it is recommended that Canadians attain and maintain a healthy body mass index. For those who choose to drink alcohol intake should be limited to 2 or fewer standard drinks per day (maximum of 14/week for men and 9/week for women). Adults should exercise regularly. (3) To reduce blood pressure in hypertensive patients, individualized therapy is recommended. This therapy should emphasize weight loss for overweight patients, abstinence from or moderation in alcohol intake, regular exercise, restriction of sodium intake and, in appropriate circumstances, individualized cognitive behaviour modification to reduce the negative effects of stress. VALIDATION: The recommendations were reviewed by all of the sponsoring organizations and by participants in a satellite symposium of the fourth international Conference on Preventive Cardiology. They are similar to those of the World Hypertension League and the Joint National committee, with the exception of the recommendations on stress management, which are based on new information. They have not been clinically tested. SPONSORS: The Canadian Hypertension Society, the Canadian Coalition for High Blood Pressure Prevention and Control, the Laboratory Centre for Disease Control at health Canada, and the Heart and Stroke Foundation of Canada.

Adult↗

Lifestyle modifications to prevent and control hypertension. 6. Recommendations on potassium, magnesium and calcium. Canadian Hypertension Society, Canadian Coalition for High Blood Pressure Prevention and Control, Laboratory Centre for Disease Control at Health Canada, Heart and Stroke Foundation of Canada.

OBJECTIVE: To provide updated, evidence-based recommendations on the consumption, through diet, and supplementation of the cations potassium, magnesium and calcium for the prevention and treatment of hypertension in otherwise healthy adults (except pregnant women). OPTIONS: Dietary supplementation with cations has been suggested as an alternative or adjunctive therapy to antihypertensive medications. Other options include other nonpharmacologic treatments for hypertension. OUTCOMES: The health outcomes considered were changes in blood pressure and in morbidity and mortality rates. Because of insufficient evidence, no economic outcomes were considered. EVIDENCE: A MEDLINE search was conducted for the period 1966-1996 with the terms hypertension and potassium, magnesium and calcium. Reports of trials, meta-analyses and review articles were obtained. Other relevant evidence was obtained from the reference lists of articles identified, from the personal files of the authors and through contacts with experts. The articles were reviewed, classified according to study design, and graded according to the level of evidence. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and premature death caused by untreated hypertension. BENEFITS, HARMS AND COSTS: The weight of the evidence from randomized controlled trials indicates that increasing intake of or supplementing the diet with potassium, magnesium or calcium is not associated with prevention of hypertension, nor is it effective in reducing high blood pressure. Potassium supplementation may be effective in reducing blood pressure in patients with hypokalemia during diuretic therapy. RECOMMENDATIONS: For the prevention of hypertension, the following recommendations are made: (1) The daily dietary intake of potassium should be 60 mmol or more, because this level of intake has been associated with a reduced risk of stroke-related mortality. (2) For normotensive people obtaining on average 60 mmol of potassium daily through dietary intake, potassium supplementation is not recommended as a means of preventing an increase in blood pressure. (3) For normotensive people, magnesium supplementation is not recommended as a means of preventing an increase in blood pressure. (4) For normotensive people, calcium supplementation above the recommended daily intake is not recommended as a means of preventing an increase in blood pressure. For the treatment of hypertension, the following recommendations are made. (5) Potassium supplementation above the recommended daily dietary intake of 60 mmol is not recommended as a treatment for hypertension. (6) Magnesium supplementation is not recommended as a treatment for hypertension. (7) Calcium supplementation above the recommended daily dietary intake is not recommended as a treatment for hypertension. VALIDATION: These guidelines are consistent with the results of meta-analyses and recommendations made by other organizations. They have not been clinically tested. SPONSORS: The Canadian Hypertension Society, the Canadian Coalition for High Blood Pressure Prevention and Control, the Laboratory Centre for Disease Control at Health Canada, and the Heart and Stroke Foundation of Canada.

Adult↗

Left ventricular mass index increase in early renal disease: impact of decline in hemoglobin.

Cardiovascular disease occurs in patients with progressive renal disease both before and after the initiation of dialysis. Left ventricular hypertrophy (LVH) is an independent predictor of morbidity and mortality in dialysis populations and is common in the renal insufficiency population. LVH is associated with numerous modifiable risk factors, but little is known about LV growth (LVG) in mild-to-moderate renal insufficiency. This prospective multicenter Canadian cohort study identifies factors associated with LVG, measured using two-dimensional-targeted M-mode echocardiography. Eight centers enrolled 446 patients, 318 of whom had protocol-mandated clinical, laboratory, and echocardiographic measurements recorded. We report 246 patients with assessable echocardiograms at both baseline and 12 months with an overall prevalence of LVH of 36%. LV mass index (LVMI) increased significantly (>20% of baseline or >20 g/m2) from baseline to 12 months in 25% of the population. Other than baseline LVMI, no differences in baseline variables were noted between patients with and without LVG. However, there were significant differences in decline of Hgb level (-0.854 v -0.108 g/dL; P = 0.0001) and change in systolic blood pressure (+6.50 v -1.09 mm Hg; P = 0.03) between the groups with and without LVG. Multivariate analysis showed the independent contribution of decrease in Hgb level (odds ratio [OR], 1.32 for each 0.5-g/dL decrease; P = 0.004), increase in systolic blood pressure (OR, 1.11 for each 5-mm Hg increase; P = 0.01), and lower baseline LVMI (OR, 0.85 for each 10-g/m2; P = 0.011) in predicting LVG. Thus, after adjusting for baseline LVMI, Hgb level and systolic blood pressure remain independently important predictors of LVG. We defined the important modifiable risk factors. There remains a critical need to establish optimal therapeutic strategies and targets to improve clinical outcomes.

Anemia↗

Conservative treatment to slow deterioration of renal function: evidence-based recommendations.

Despite current specific therapy, progressive deterioration of renal function in patients with primary glomerulonephritis occurs. Nonspecific renoprotective interventions that have been studied include blood pressure control, antihypertensive medications, and protein-restricted diets. To prepare this article, a MEDLINE search was conducted, followed by secondary and tertiary searches. Research papers were assessed for level of evidence, and graded recommendations were formulated. Protein-restricted diets (to 0.4 to 0.6 g/kg/day) are not recommended for all patients with reduced renal function (grade A). Very low-protein diets of 0.4 g/kg/day should be considered for patients with severe renal dysfunction (serum creatinine of more than 350 micromol/liter; grade A). However, there are concerns about recommending these diets for all patients because of the potential for long-term negative outcomes such as nutritional deficiencies. Target blood pressure for persons with proteinuria of more than 1 g/day should be less than 125/75 mm Hg [mean arterial pressure (MAP) < 92 mm Hg; grade C]. For persons with proteinuria of less than 1 g/day, the target blood pressure should be approximately MAP 98 mm Hg (less than 130/80; grade C). Angiotensin-converting enzyme inhibitor (ACEI) therapy is recommended in preference to placebo, conventional, or beta-blocker therapy for renoprotection (grade A). ACEI therapy cannot be recommended above calcium channel blockers in patients with nondiabetic renal disease (grade A).

Antihypertensive Agents↗

Management of focal segmental glomerulosclerosis: evidence-based recommendations.

Focal segmental glomerulosclerosis (FSGS) is a diagnosis based on the presence of glomeruli with segmental scarring in association with intracapillary foam cells and adhesions. To develop evidence-based treatment guidelines, a MEDLINE search was conducted, and articles were reviewed using levels of evidence. Graded recommendations were developed according to the level of evidence. There was limited evidence found on which to develop recommendations. Treatment with prednisone of 0.5 to 2 mg/kg/day should be considered in all patients and continued for six months before declaring the patient resistant to therapy. Remission is associated with the use of high doses (more than 60 mg/day) for three months; therefore, if there is a concern about prolonged use, a reduction in dose to 0.5 mg/kg/day should be made only after three months (grade D). The use of cyclosporine A (CsA) at doses to maintain serum levels at 150 to 300 microg/ml may be effective in reducing urinary protein excretion. Relapse after reducing or stopping CsA is very common. Long-term use may be required to maintain remission (grade D). The use of cytotoxic therapy (cyclophosphamide, azathioprine, and chlorambucil) for adults is second-line therapy (grade D). Plasmapheresis or protein adsorption may be recommended for renal transplant patients with recurrent FSGS (grade D).

Adult↗

The use of antiretroviral agents in patients with renal insufficiency.

Current guidelines for the dosing of antiretroviral agents in HIV-positive patients with renal insufficiency including those requiring dialysis are limited, as revealed by a literature search performed using Health Knowledge Network MEDLINE and HealthSTAR. Pharmacokinetic and chemical aspects were taken into consideration to develop further recommendations. Results showed reverse transcriptase inhibitor dosage adjustment guidelines are available, but for patients receiving dialysis, guidelines are limited to zidovudine and didanosine. There are limited clinical data on dosage adjustments required for the use of protease inhibitors or non-nucleoside reverse transcriptase inhibitors (NNRTIs). Indinavir appears to require no dose modification. For nelfinavir, ritonavir and saquinavir, the chemical and pharmacokinetic characteristics along with the pathophysiology of renal dysfunction and dialysis suggest that these agents can likely be given at usual doses with close monitoring for toxicities. More data is required to make recommendations for use of NNRTIs in renal insufficiency. Combining the information from previous dosing guidelines and the pharmacokinetic data of antiretroviral agents allows for preliminary recommendations to be made until confirmed by definitive clinical data.

Anti-HIV Agents↗