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Hypertension Canada’s 2020 guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children provide comprehensive, evidence-based guidance for health care professionals and patients. Hypertension Canada develops the guidelines using rigourous methodology, carefully mitigating the risk of bias in our process. All draft recommendations undergo critical review by expert methodologists without conflict to ensure quality. Our guideline panel is diverse, including multiple health professional groups (nurses, pharmacy, academics, and physicians), and worked in concert with experts in primary care and implementation to ensure optimal usability. The 2020 guidelines include new guidance on the management of resistant hypertension and the management of hypertension in women planning pregnancy.

Hypertension Canada provides annually updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension in adults and children. This year, the adult and pediatric guidelines are combined in one document. The new 2018 pregnancy-specific hypertension guidelines are published separately. For 2018, 5 new guidelines are introduced, and 1 existing guideline on the blood pressure thresholds and targets in the setting of thrombolysis for acute ischemic stroke is revised. The use of validated wrist devices for the estimation of blood pressure in individuals with large arm circumference is now included. Guidance is provided for the follow-up measurements of blood pressure, with the use of standardized methods and electronic (oscillometric) upper arm devices in individuals with hypertension, and either ambulatory blood pressure monitoring or home blood pressure monitoring in individuals with white coat effect. We specify that all individuals with hypertension should have an assessment of global cardiovascular risk to promote health behaviours that lower blood pressure. Finally, an angiotensin receptor-neprilysin inhibitor combination should be used in place of either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in individuals with heart failure (with ejection fraction < 40%) who are symptomatic despite appropriate doses of guideline-directed heart failure therapies. The specific evidence and rationale underlying each of these guidelines are discussed.

Hypertension Canada provides annually updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension. This year, we introduce 10 new guidelines. Three previous guidelines have been revised and 5 have been removed. Previous age and frailty distinctions have been removed as considerations for when to initiate antihypertensive therapy. In the presence of macrovascular target organ damage, or in those with independent cardiovascular risk factors, antihypertensive therapy should be considered for all individuals with elevated average systolic nonautomated office blood pressure (non-AOBP) readings ≥ 140 mm Hg. For individuals with diastolic hypertension (with or without systolic hypertension), fixed-dose single-pill combinations are now recommended as an initial treatment option. Preference is given to pills containing an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in combination with either a calcium channel blocker or diuretic. Whenever a diuretic is selected as monotherapy, longer-acting agents are preferred. In patients with established ischemic heart disease, caution should be exercised in lowering diastolic non-AOBP to ≤ 60 mm Hg, especially in the presence of left ventricular hypertrophy. After a hemorrhagic stroke, in the first 24 hours, systolic non-AOBP lowering to < 140 mm Hg is not recommended. Finally, guidance is now provided for screening, initial diagnosis, assessment, and treatment of renovascular hypertension arising from fibromuscular dysplasia. The specific evidence and rationale underlying each of these guidelines are discussed.

Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force provides annually updated, evidence-based recommendations to guide the diagnosis, assessment, prevention, and treatment of hypertension. This year, we present 4 new recommendations, as well as revisions to 2 previous recommendations. In the diagnosis and assessment of hypertension, automated office blood pressure, taken without patient-health provider interaction, is now recommended as the preferred method of measuring in-office blood pressure. Also, although a serum lipid panel remains part of the routine laboratory testing for patients with hypertension, fasting and nonfasting collections are now considered acceptable. For individuals with secondary hypertension arising from primary hyperaldosteronism, adrenal vein sampling is recommended for those who are candidates for potential adrenalectomy. With respect to the treatment of hypertension, a new recommendation that has been added is for increasing dietary potassium to reduce blood pressure in those who are not at high risk for hyperkalemia. Furthermore, in selected high-risk patients, intensive blood pressure reduction to a target systolic blood pressure ≤ 120 mm Hg should be considered to decrease the risk of cardiovascular events. Finally, in hypertensive individuals with uncomplicated, stable angina pectoris, either a β-blocker or calcium channel blocker may be considered for initial therapy. The specific evidence and rationale underlying each of these recommendations are discussed. Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force will continue to provide annual updates.

The Canadian Hypertension Education Program reviews the hypertension literature annually and provides detailed recommendations regarding hypertension diagnosis, assessment, prevention, and treatment. This report provides the updated evidence-based recommendations for 2015. This year, 4 new recommendations were added and 2 existing recommendations were modified. A revised algorithm for the diagnosis of hypertension is presented. Two major changes are proposed: (1) measurement using validated electronic (oscillometric) upper arm devices is preferred over auscultation for accurate office blood pressure measurement; (2) if the visit 1 mean blood pressure is increased but < 180/110 mm Hg, out-of-office blood pressure measurements using ambulatory blood pressure monitoring (preferably) or home blood pressure monitoring should be performed before visit 2 to rule out white coat hypertension, for which pharmacologic treatment is not recommended. A standardized ambulatory blood pressure monitoring protocol and an update on automated office blood pressure are also presented. Several other recommendations on accurate measurement of blood pressure and criteria for diagnosis of hypertension have been reorganized. Two other new recommendations refer to smoking cessation: (1) tobacco use status should be updated regularly and advice to quit smoking should be provided; and (2) advice in combination with pharmacotherapy for smoking cessation should be offered to all smokers. The following recommendations were modified: (1) renal artery stenosis should be primarily managed medically; and (2) renal artery angioplasty and stenting could be considered for patients with renal artery stenosis and complicated, uncontrolled hypertension. The rationale for these recommendation changes is discussed.

Herein, updated evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in Canadian adults are detailed. For 2014, 3 existing recommendations were modified and 2 new recommendations were added. The following recommendations were modified: (1) the recommended sodium intake threshold was changed from ≤ 1500 mg (3.75 g of salt) to approximately 2000 mg (5 g of salt) per day; (2) a pharmacotherapy treatment initiation systolic blood pressure threshold of ≥ 160 mm Hg was added in very elderly (age ≥ 80 years) patients who do not have diabetes or target organ damage (systolic blood pressure target in this population remains at < 150 mm Hg); and (3) the target population recommended to receive low-dose acetylsalicylic acid therapy for primary prevention was narrowed from all patients with controlled hypertension to only those ≥ 50 years of age. The 2 new recommendations are: (1) advice to be cautious when lowering systolic blood pressure to target levels in patients with established coronary artery disease if diastolic blood pressure is ≤ 60 mm Hg because of concerns that myocardial ischemia might be exacerbated; and (2) the addition of glycated hemoglobin (A1c) in the diagnostic work-up of patients with newly diagnosed hypertension. The rationale for these recommendation changes is discussed. In addition, emerging data on blood pressure targets in stroke patients are discussed; these data did not lead to recommendation changes at this time. The Canadian Hypertension Education Program recommendations will continue to be updated annually.

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2013. This year's update includes 2 new recommendations. First, among nonhypertensive or stage 1 hypertensive individuals, the use of resistance or weight training exercise does not adversely influence blood pressure (BP) (Grade D). Thus, such patients need not avoid this type of exercise for fear of increasing BP. Second, and separately, for very elderly patients with isolated systolic hypertension (age 80 years or older), the target for systolic BP should be < 150 mm Hg (Grade C) rather than < 140 mm Hg as recommended for younger patients. We also discuss 2 additional topics at length (the pharmacological treatment of mild hypertension and the possibility of a diastolic J curve in hypertensive patients with coronary artery disease). In light of several methodological limitations, a recent systematic review of 4 trials in patients with stage 1 uncomplicated hypertension did not lead to changes in management recommendations. In addition, because of a lack of prospective randomized data assessing diastolic BP thresholds in patients with coronary artery disease and hypertension, no recommendation to set a selective diastolic cut point for such patients could be affirmed. However, both of these issues will be examined on an ongoing basis, in particular as new evidence emerges.

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2012. The new recommendations are: (1) use of home blood pressure monitoring to confirm a diagnosis of white coat syndrome; (2) mineralocorticoid receptor antagonists may be used in selected patients with hypertension and systolic heart failure; (3) a history of atrial fibrillation in patients with hypertension should not be a factor in deciding to prescribe an angiotensin-receptor blocker for the treatment of hypertension; and (4) the blood pressure target for patients with nondiabetic chronic kidney disease has now been changed to < 140/90 mm Hg from < 130/80 mm Hg. We also reviewed the recent evidence on blood pressure targets for patients with hypertension and diabetes and continue to recommend a blood pressure target of less than 130/80 mm Hg.

Hypertension is prevalent in patients with type 2 diabetes mellitus and contributes to substantial morbidity and mortality. Preventing microalbuminuria (MAU) is important in these patients because MAU is associated with an increased risk of end-stage renal disease and cardiovascular events. Current hypertension treatment recommendations are based on drug ‘class’ effects. For the treatment of hypertension in patients with diabetes, important agent-specific effects should be brought into consideration in the choice of drug. For these patients, and especially in the presence of kidney disease, the choice of agent must effectively target not only blood pressure reduction, but also prevention and treatment of MAU for optimal organ outcomes. A review of the current evidence suggests a diversity of MAU-associated risk reduction according to agent within the angiotensin receptor blocker and angiotensin-converting enzyme inhibitor classes, ranging from nonefficacy to significant efficacy. Recommendations should clearly state absolute risk reduction according to agent, based on the best available evidence.

To update the evidence-based recommendations for the prevention and treatment of hypertension in adults for 2010.

To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with hypertension.

To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with hypertension.

To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with hypertension.

To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with hypertension.

Atherosclerotic renovascular disease is a combination of renal artery stenosis and renal ischemia. Blood pressure does not rise until the stenosis is 60% or greater. Disease of both large and small blood vessels is often accompanied by the loss of glomerular filtration rate. Activation of the renin-angiotensin-aldosterone system leads to vasoconstriction and salt retention.

To provide updated, evidence-based recommendations for the management of hypertension in adults.

To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with high blood pressure.

Appreciation of the role of aldosterone in cardiovascular and renal disease has increased in the last 50 years. The use of spironolactone was limited by adverse sexual effects, including gynaecomastia. Eplerenone is a newer aldosterone antagonist that is much more selective, with minimal affinity for progesterone and androgenic receptors; therefore, there are very few reports of adverse sexual effects. A review of published trials shows that eplerenone reduces blood pressure (BP) in a dose-dependent manner, from 50 to 200 mg/day, and to a similar degree as enalapril. It has an additive effect when given to patients inadequately controlled on an angiotensin-converting enzyme inhibitor or an angiotensin-receptor blocker. Eplerenone performs better than losartan in African-American patients and lowers BP regardless of initial plasma renin activity. The risk of hyperkalaemia is low, similar to that of enalapril, and < 1% of patients have had to be withdrawn from studies because of elevated serum potassium levels. Eplerenone is an effective, well-tolerated antihypertensive agent that may be used alone or in conjunction with other agents; apart from the risk of hyperkalaemia, adverse effects are similar to placebo.

Purpose: The first criteria for the determination of brain death were developed in 1968 in part to address concerns that had arisen with the retrieval of organs for transplantation. Despite over 30 years of application, some professional and public doubt persists over the validity of the theoretical construct underlying this method of determining death. Our review will address historical perspectives on the development of brain death criteria, and inconsistencies in current clinical criteria. Method: Narrative review from selected MEDLINE references and other published sources. Principal findings: The primary construct of the determination of death is that either cardiopulmonary or neurological function irreversibly ceases. However, there is inconsistency in the neurological criteria for death between jurisdictions, between patient populations, and in the use of confirmatory tests. These inconsistencies may cause concern in the public or profession about the validity of the determination of death by neurological criteria. Conclusions: Organ transplantation is premised on professional and public acceptance that the donor is dead. Given that the criteria for brain death or their application remain variable, we suggest that it is reasonable to consider a national consensus to address these inconsistencies. Alternatively, the standard use of confirmatory radiographie testing prior to the retrieval of organs from donors who meet clinical brain death criteria should be considered to provide conclusive evidence of permanent and irreversible loss of brain function.

The aim of the current study was to examine, through posthoc analyses, changes in and predictive utility of mood–related cognitive variables as a function of treatment modality in a group of alcohol dependent patients with elevated depressive symptoms. In addition to the background partial hospital treatment for alcoholism which lasted a mean of 21.2 days, study patients (n = 35) received cognitive–behavioral treatment for depression (CBT–D) or a control treatment consisting of relaxation training (RTC). While both groups showed improvement on dysfunctional attitudes during treatment, only the CBT–D group improved on measures of alcohol–related expectancies. Changes in cognitive variables during treatment predicted drinking outcomes, and the predictors of drinking outcomes varied across the two treatments. Among the RTC patients, changes in positive alcohol–related expectancies were negatively correlated with drinking frequency and quantity at follow–up. However, for the CBT–D patients, changes in self–efficacy concerning negative mood situations and negative alcohol–related expectancies were negatively correlated with drinking at longer–term follow–up. The results of this study provide evidence concerning the mechanisms by which the treatment modalities examined may affect patient outcome. Although these results are preliminary in nature, they do suggest that future research might examine efforts to capitalize on these mechanisms through the facilitation of changes found to predict better drinking outcomes in this study.

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. © 2001 by the National Kidney Foundation, Inc.

Substance use disorders, particularly those involving alcohol, marijuana, and cocaine, are highly prevalent among patients with schizophrenia and contribute markedly to its overall morbidity. Unfortunately, standard (typical) antipsychotic medications do not seem to reduce substance use in patients with schizophrenia and may even increase it. Recently, however, a few anecdotal case reports and two previous small "N" surveys have found that clozapine, an atypical antipsychotic medication, seems to decrease substance use in patients treated with this drug for their psychoses. The authors report data from a retrospective survey of substance use in 58 patients treated with clozapine who had a history of comorbid schizophrenia (or schizoaffective disorder) and substance use disorder. Of these 58 patients, 43 were being treated with clozapine at the time of the survey; the remaining 15 patients had discontinued clozapine before the survey. The survey involved chart review and clinician interview to assess change in substance use and global clinical symptoms while receiving treatment with clozapine. More than 85% of the patients who were active substance users at the time of initiation of treatment with clozapine decreased their substance use over the course of clozapine administration. For patients who continued treatment with clozapine up to the present, the decrease in substance use was strongly correlated with a decrease in global clinical symptoms. Data from this retrospective survey further support the previous observations that clozapine reduces substance use among patients with schizophrenic disorders. Moreover, the data suggest the need for prospective controlled studies of the effects of clozapine on substance use in this population.

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.

Hyperhomocyst(e)inemia is now recognized as an independent risk factor for atherosclerotic cardiovascular disease in patients with normal renal function. Hyperhomocyst(e)inemia is common in patients with chronic renal failure. This study is designed to look for an association between hyperhomocyst(e)inemia and atherosclerotic vascular disease in patients with end-stage renal disease (ESRD). Two hundred eighteen patients undergoing hemodialysis were enrolled onto the study and had predialysis bloodwork performed for total homocyst(e)ine, red blood cell folate, and vitamin B12levels. A history of clinically significant atherosclerotic vascular disease (ischemic heart disease, cerebrovascular disease, or peripheral vascular disease) was elicited by patient questionnaire and verified by careful inpatient and outpatient chart review. Atherosclerotic vascular disease was present in 45.9% of patients. Mean homocyst(e)ine concentration was 26.7 μmol/L (95% confidence interval [CI], 25.0 to 28.4) overall. Mean homocyst(e)ine concentration was 28.6 μmol/L (95% CI, 25.6 to 31.7) and 25.0 μmol/L (95% CI, 23.2 to 26.8) in patients with and without atherosclerotic disease, respectively (P= 0.036). The adjusted odds ratio for atherosclerotic disease was 2.12 (95% CI, 1.03 to 4.39) for those subjects with a homocyst(e)ine level in the highest quartile compared with the lowest 3 quartiles. In the 126 men, the adjusted odds ratio for atherosclerotic disease was 3.4 (95% CI, 1.24 to 9.42) for those with homocyst(e)ine levels in the highest quartile compared with the lowest 3 quartiles. No association was found between homocyst(e)ine level and atherosclerotic disease in women. In conclusion, there is an association between hyperhomocyst(e)inemia and atherosclerotic vascular disease in patients undergoing dialysis. Prospective studies need to further examine the relationship between homocyst(e)ine level and atherosclerosis in women with ESRD.

The pharmacokinetics of flecainide acetate were studied in 20 patients with varying degrees of renal impairment following a single oral dose. The patients were divided into two groups, on the basis of renal creatinine clearance (CLCR), for statistical and kinetic analysis. Patients with a CLCRbetween 4 and 41 mL/min/m2were designated group 1 and those below 4 mL/min/m2or unmeasurable because of lack of urine output were designated group 2. In both groups peak plasma flecainide concentrations, time to peak concentrations, and apparent volume of distribution (Vd) were similar to those reported in healthy subjects with normal renal function. The mean flecainide plasma elimination half‐lives from both groups 1 and 2 were longer than those previously reported by several investigators in normal subjects. Nine patients in group 1 and seven patients in group 2 had half‐lives within the range reported in healthy subjects. Therefore, CLCRalone is not a good predictor of plasma elimination half‐life following a single oral dose of flecainide. Although renal clearance of flecainide is significantly reduced in end‐stage renal disease (ESRD), total plasma clearance of flecainide (CLflec) was not reduced to the same degree, although there was a significant, modest correlation with CLCR. Less than 1% of the administered oral dose of flecainide was removed during hemodialysis. The relationship between dosage and plasma elimination half‐life in patients with ESRD needs further study to evaluate possible dose‐dependent kinetics.

Drugs used in the treatment of peptic ulcer disease may interact with the renal system in a variety of ways. Since many agents are eliminated by renal excretion, clearance of these agents may be reduced and half-life extended in the presence of renal insufficiency. The histamine H2-receptor antagonists may interfere with renal tubular excretion of creatinine and cationic drugs, resulting in elevated serum concentrations and reduced renal clearance. The prostaglandin E1analogue misoprostol is used as a cytoprotective agent but has renal effects. The renal effects differ between systems studied. In the rat, misoprostol reduces cyclosporin-induced renal tubular toxicity, whereas in humans it has been shown to attenuate renal allograft rejection. Sucralfate is the aluminium salt of sucrose octasulfate. It permits the absorption of aluminium in amounts similar to aluminium-containing antacids, and toxicity has been demonstrated in the presence of renal insufficiency. Bismuth compounds are used increasingly to treat peptic ulcer disease, and bismuth toxicity has been described in association with renal insufficiency. Aluminium-, calcium- and magnesium-containing antacids are used as oral phosphate binders in patients with renal insufficiency in addition to their usual indications. Cation absorption and accumulation with all of these antacid preparations has been described and may lead to toxicity.

End-stage renal disease (ESRD) is recognized as imposing severe psychosocial stresses upon patients with the result that depression is believed to be highly prevalent. A number of studies have reported low levels of depression, however, and this contradictory finding has been explained via the construct of defensive denial-i.e., patients may minimize the impact of illness-related experiences upon their overall experiences of life. The present study tested this hypothesis in a sample of seventy ESRD patients. Participants rated a series of twelve life dimensions (e.g., work, family and marital relations, recreation) in terms of perceived intrusiveness and control as well as indicating their perceived similarity using a card sort task. Standard measures of depression, positive and negative moods, somatic symptoms of distress, self-esteem, and life happiness were also obtained via structured interviews. A multidimensional scaling analysis applied to the card sort data indicated that ESRD patients do, indeed, perceive illness-related and nonillness aspects of life as independent. However, an analysis of partial variance-controlling for age and nonrenal health-failed to provide evidence of defensive denial. The suggestion is forwarded that previous findings of a high prevalence of depression in ESRD may be in error due to the misidentification of uremic symptoms as symptoms of depression.

Kinetics of sotalol, a beta adrenoceptor blocker, was studied in 20 patients with varying renal function. In subjects with creatinine clearance (Clcr) ≥ 39 ml/min/m2, sotalol plasma clearance (\[xmacr] ± SD) was 71 ± 31 ml/min/m2, elimination half-life (t½) was 8.1 ± 3.4 hr, and renal clearance was 46 ± 26 ml/min/m2. In patients with moderate renal impairment (Clcr= 8 to 38 ml/min/m2) elimination t½ rose to 24.2 ± 7.5 hr, and plasma clearance fell to 24 ± 7 ml/min/m2. In patients receiving dialysis, elimination t½ rose to 33.9 ± 27.1 hr. Elimination t½ during hemodialysis was 5.8 ±2.1 hr and was associated with a 56.7 ± 21% reduction in plasma levels.Clinical Pharmacology and Therapeutics (1981) 29, 457–463; doi:10.1038/clpt.1981.63

In this study of the toxicokinetics of aluminum we have examined some of the fundamental issues that currently define our understanding of the toxicology of aluminum in humans. There is a vast literature on this subject, and it was not our aim to review this literature but to use it to develop our understanding of the toxicokinetics of aluminum and to identify critical and unresolved issues related to its toxicity. In undertaking this task we have chosen to define the term toxicokinetics to encompass those factors that influence both the lability of aluminum in a body and the sites at which aluminum is known to accumulate, with or without consequent biological effect. We have approached our objective from the classical pharmacological approach of ADME: the absorption, distribution, metabolism, and excretion of aluminum. This approach was successful in identifying several key deficits in our understanding of aluminum toxicokinetics. For example, we need to determine the mechanisms by which aluminum crosses epithelia, such as those of the gastrointestinal tract and the central nervous system, and how these mechanisms influence both the subsequent transport and fate of the absorbed aluminum and the concomitant nature and severity of the biological response to the accumulation of aluminum. Our hope in highlighting these unresolved issues (summarized in Table 1) is that they will be addressed in future research.

Several psychosocial variables were investigated as predictors of 4-year survival in a sample of 97 end-stage renal disease (ESRD) patients undergoing treatment by hemodialysis, continuous ambulatory peritoneal dialysis, or renal transplantation. Hypothesized psychosocial predictors included depression, mood disturbance, life happiness, affect, pessimism, self-esteem, knowledge of renal disease and its treatment, perceived control over important life domains, perceived intrusiveness of ESRD into important life domains, illness-related concerns, difficulties in daily activities, number of regular leisure activities, somatic symptoms of distress, social networks, recent negative life events, and defensive response styles. Methodological controls were incorporated to test the prognostic significance of these variables and included a) exclusion of deaths attributable to “unnatural” causes; b) multivariate statistical controls for physical and demographic determinants of survival; c) widely used standardized psychosocial instruments; and d) temporally aggregated psychosocial measurements to enhance reliability. Hierarchical multiple regression analyses identified four variables as significant and independent predictors of increased survival times in ESRD: a) comparatively fewer serious nonrenal comorbid illnesses; b) younger age; c) regular involvement in an increased number of leisure activities; and d) overall life happiness described as “an even mixture of unhappiness and happiness” (as compared with “very happy”). However, no evidence was obtained to support the hypothesis that increased depressive symptoms and/or moods contribute to compromised survival in ESRD

During a longitudinal study of the quality of life of end-stage renal disease, 204 patients with deteriorating renal function were identified before dialysis or transplantation was required to preserve their lives. These patients were randomly assigned to either an enhanced or a standard education condition. The enhanced education condition consisted of a specially prepared slide-lecture show concerning kidney diseases and their treatment that was delivered by a trained research assistant. The standard education condition consisted of whatever educational procedures were routinely available at the participating hospital. All but six patients have now started treatment by maintenance dialysis. Individuals in the enhanced education condition survived an average of 4.6 months longer than did those in the standard education group without requiring the initiation of renal replacement therapy. This effect could not be attributed to physical differences between the groups, to cohort effects, to delays in contacting the patients, or to when or where they were identified. Possible mechanisms for this effect are discussed.

Cognitive theory ascribes nonendogenous depression to latent dysfunctional beliefs activated by Stressors impinging upon core values (e.g., rejection for a sociotropic person). To address ambiguities in past tests of the theory, this study measured personality (Sociotropy-Autonomy Scale) and recent Stressors (Life Experience Survey and Hassles Scale) among 14 Gushing syndrome patients and 12 controls. Patients scored nonsignificantly higher in sociotropy, and sociotropy correlated positively with depression among patients. Because depression in Gushing syndrome presumably results from biological dysfunction rather than from the interaction of personality and relevant Stressors, these results imply that sociotropy may be a consequence of depression as opposed to a contributory cause. There was no congruence between personality and types of Stressors reported, which suggests that mood-dependent recall does not account for past evidence of congruence.

Twenty-five subjects, divided into four groups according to their creatinine clearance, each received a 0.5 g intravenous dose of ceftizoxime over 1 to 2 min in order to determine the pharmacokinetics of parenteral ceftizoxime in subjects with various degrees of renal insufficiency and of high doses of parenteral ceftizoxime in subjects with normal renal function. Blood and urine samples were taken periodically and measured for drug concentration (in serum, by well-plate diffusion and in urine, by high performance liquid chromatography). The mean pharmacokinetic parameters were calculated, and the data compared. Ceftizoximes relatively small steady-state volume of distribution throughout the body is not altered in renal disease. No concentration-dependent kinetics are indicated since the data did not vary significantly over a wide dosage range. Ceftizoxime is eliminated primarily by the kidneys and has a prolonged serum half-life in patients with end-stage renal disease so that dosage should be adjusted for patients with moderate-to-severe renal impairment. The protein binding of ceftizoxime in subjects with normal renal function is 31%; the haemodialysis clearance of ceftizoxime is 44.8 ± 21.5 ml/min. Supplemental dosage of ceftizoxime is not necessary after haemodialysis.

Posttraumatic stress disorder (PTSD) is a psychological consequence of traumatic work-related hand injury. In the current study, we investigated this relationship by examining the prevalence, of PTSD symptoms in 121 Worker's Compensation patients enrolled in a work rehabilitation program following a wide array of work-related injuries. Eighty-eight men and 33 women, ranging in age from 16 to 78 (M=40.9,SD=10.2), completed the Injury Adjustment Survey, a measure of PTSD symptoms, psychological/behavioral changes following injury, and desire for psychological treatment. We found that the majority of patients reported difficulties sleeping, a diminished sense of future, loss of interest, and increased anger. Twenty percent of patients endorsed symptoms from criteria B (reexperiencing the trauma), C (persistent avoidance or numbing), and D (inreased arousal) for PTSD according to the DSM-IV. PTSD symptoms did not significantly, relate to age, gender, locations of injury, type of injury, seeing the injury occur, or length of time since injury. PTSD symptoms did significantly relate to psychological/behavioral changes or difficulties and the desire to seek psychological treatment. Discussion of the results proceeds from within a psychotraumatological framework. In general, our research confirmed that PTSD symptoms appear to be a clinically significant problem for patients suffering from a variety of work-related injuries.

The prevention and treatment of aluminum (Al) accumulation and toxicity are reviewed. Recommendations to further our understanding of desferrioxamine (deferoxamine, DFO) treatment and to develop more effective chelation approaches are provided. Reduction of Al accumulation and toxicity may benefit end-stage renal disease (ESRD) patients and perhaps those suffering from specific neurodegenerative disorders as well as workers with Alinduced neurocognitive disorders. The clearance of Al may be increased by extracorporeal chelation, renal transplantation, perhaps complexation with simple ligands such as silicon (Si), and systemic chelation therapy. The abilities of extracorporeal chelation and Si to reduce Al accumulation require further evaluation. Although it may not be possible to design Al-specific chelators, chelators with greater Al selectivity are desired. Aluminumselective chelation might be achieved by targeted chelator distribution or by the use of adjuvants with the chelator. The ability of carboxylic acids to facilitate Al elimination, under specific conditions, warrants further study. Desferrioxamine does not produce significant biliary Al excretion. A chelator with this property may be useful in ESRD patients. The necessity for an Al chelator to distribute extravascularly to be effective is unknown and should be determined to guide the selection of alternatives to DFO. The lack of oral efficacy and occasional side effects of DFO encourage identification of orally effective, safer Al chelators. The bidentate 3-hydroxypyridin-4-ones are currently the most encouraging alternatives to DFO. They have been shown to increase urinary Al excretion in rats and rabbits, but to have toxicity comparable to, or greater than, DFO. Their toxicity may relate to incomplete metal complexation. The ability of orally effective chelators to increase absorption of chelated metal from the gastrointestinal (GI) tract needs to be evaluated. Orally effective, safe Al chelators would be of benefit to peritoneal dialysis patients and those with neurodegenerative disorders, if Al chelation therapy is indicated. The reduction of Alzheimer's disease (AD) progression and the reversal of Al-induced behavioral deficits and neurofibrillary tangles by DFO encourage further study of Al chelation therapy for selected neurodegenerative disorders.

Sodium sensitivity in subjects with high-renin hypertension has been associated with non-modulation of cardiovascular and biochemical responses to alteration in sodium intake. Using the percentage suppression of plasma renin activity in response to an increase in dietary sodium intake, high-renin hypertensive subjects were categorized in two groups, tn association with the increase in sodium intake, modulators showed >58 suppression of plasma renin activity, and significant reductions in mean arterial pressure, plasma aldosterone, norepinephrine and serum calcium concentration. Non-modulators had no significant change in plasma renin activity, mean arterial blood pressure, plasma aldosterone, norepinephrine or serum calcium concentration. The blood pressure response to an increase in dietary sodium intake may be a composite of responses of the renin-angiotensin-aldosterone axis, the adrenergic nervous system and calcium regulatory system.

The pharmacokinetics of a single intravenous dose of propafenone were studied in subjects with normal renal function (n = 5), renal insufficiency (n = 5), and renal failure (n = 3). No difference in central volume of distribution, total systemic clearance or terminal half‐life existed. None of the pharmacokinetic parameters examined correlated to creatinine clearance. Within the confines of the small number of patients studied, there does not appear to be any effect of renal insufficiency or failure on single‐dose propafenone disposition.

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2011. The major guideline changes this year are: (1) a recommendation was made for using comparative risk analogies when communicating a patient's cardiovascular risk; (2) diagnostic testing issues for renal artery stenosis were discussed; (3) recommendations were added for the management of hypertension during the acute phase of stroke; (4) people with hypertension and diabetes are now considered high risk for cardiovascular events if they have elevated urinary albumin excretion, overt kidney disease, cardiovascular disease, or the presence of other cardiovascular risk factors; (5) the combination of an angiotensin-converting enzyme (ACE) inhibitor and a dihydropyridine calcium channel blocker (CCB) is preferred over the combination of an ACE inhibitor and a thiazide diuretic in persons with diabetes and hypertension; and (6) a recommendation was made to coordinate with pharmacists to improve antihypertensive medication adherence. We also discussed the recent analyses that examined the association between angiotensin II receptor blockers (ARBs) and cancer.

Medications to treat peptic ulcer disease are used widely and may have adverse effects on renal function. Similarly, renal dysfunction may alter the pharmacokinetics of this diverse group of medications resulting in dosage adjustments. The older agents, antacids and sucralfate, allow absorption of cations (calcium, magnesium and aluminum) which may result in toxicity. Newer medications (H2 blockers and omeprazole) appear to have fewer side effects and be better tolerated with appropriate dosage adjustments.