Elderly heart failure patients and the role of beta-blocker therapy

In this article different aspects of chronic heart failure in old age are described. We mainly focus on the place of beta-blocker therapy in chronic heart failure. Beta-blockers are recommended for the treatment of stable chronic heart failure with left ventricular systolic dysfunction. There is additional information from recent studies that there is proven efficacy for beta-blocker therapy in patients with heart failure up to the age of 80 years. For patients with heart failure aged 80 and over the evidence to prescribe beta-blockers is limited. However, it is known that also in very elderly patients beta-blocker therapy is well tolerated. In patients with heart failure with preserved systolic ventricular function there is still no evidence that there is a beneficial effect of beta-blockers. It is still not clear if there are differences between beta-blocking agents. Of all beta-blockers, only bisoprolol, carvedilol, nebivolol and metoprolol CR are proven effective in stable chronic heart failure with impaired left ventricular systolic function and can be recommended in elderly patients on standard treatment with diuretics and ACE inhibition.     

Use of beta-blocker therapy in older patients after acute myocardial infarction in Ontario.

BACKGROUND: Despite its proven efficacy, beta-blocker therapy remains underused in elderly patients after myocardial infarction (MI). The objectives of this study were to identify undertreated groups of seniors and to determine whether older and frailer patients are being selectively dispensed low-dose beta-blocker therapy. METHODS: From a comprehensive hospital discharge database, all people aged 66 years or more in Ontario who survived an acute MI between April 1993 and March 1995 were identified and classified into those who did not receive beta-blocker therapy and those dispensed low, standard or high doses of this agent. Logistic regression models were used to study the effect of age, sex, comorbidity, potential contraindications to beta-blocker therapy and residence in a long-term-care facility on the odds of not being dispensed a beta-blocker. Among beta-blocker users, the odds of being dispensed low relative to standard or high doses of this agent were evaluated. RESULTS: Of the 15,542 patients, 7549 (48.6%) were not dispensed a beta-blocker. Patients 85 years of age or more were at greater risk of not receiving beta-blocker therapy (adjusted odds ratio [OR] 2.8, 95% confidence interval [CI] 2.5-3.2) than were those 66 to 74 years. Having a Charlson comorbidity index of 3 or greater was associated with an increased risk of not receiving beta-blocker therapy (adjusted OR 1.5, 95% CI 1.3-1.8) compared with having lower comorbidity scores. Patients who resided in a long-term-care facility were at increased risk of not being prescribed beta-blocker therapy (adjusted OR 2.6, 95% CI 2.0-3.4). Among the 5453 patients with no identifiable contraindication to beta-blocker therapy, women were significantly less likely than men to receive this agent (p = 0.005). Of the 6074 patients who received beta-blockers, 2248 (37.0%) were dispensed low-dose therapy. Patients aged 85 years or more had an increased risk of being dispensed low-dose therapy (adjusted OR 1.6, 95% CI 1.3-2.0) compared with those aged 66 to 74 years. Compared with those who had the lowest comorbidity scores, patients with the highest comorbidity scores were more likely to be dispensed low-dose beta-blocker therapy (adjusted OR 1.3, 95% CI 1.0-1.8). INTERPRETATION: Almost half of Ontario patients aged 66 or more who survived an MI, particularly those who were older or frailer, did not receive beta-blocker therapy. Among those dispensed beta-blocker therapy, older and frailer patients were more frequently dispensed low-dose therapy.     

Beta-blocker therapy and the risk of anaphylaxis.

Beta-blocker therapy is associated with an increase in the severity and, possibly, the incidence of acute anaphylaxis. The population at risk consists of people with allergic conditions who are given a beta-blocker for an unrelated condition. Anaphylaxis under these conditions may be severe, protracted and resistant to conventional treatment because of the beta-adrenergic blockade. Severe or fatal attacks have been triggered by insect stings, the ingestion of allergenic foods or drugs, and injections of radiocontrast media, antisera or immunotherapy antigens. These occurrences are probably infrequent, but their incidence is unknown. At least two fatal cases have recently occurred in Canada. Clinical allergists, internists and family practitioners in particular should be aware of the need for aggressive and prolonged support in patients who experience anaphylaxis while receiving beta-blocker therapy and should report all such occurrences to the federal registry of adverse drug reactions. Allergy skin testing or immunotherapy is inadvisable in patients who take a beta-blocker orally or in the form of ophthalmic eyedrops. The list of relative contraindications to beta-blocker use should be extended to include susceptibility to recurrent anaphylaxis, whether it is idiopathic or due to an identifiable cause.     

Effect of Beta-Blocker Therapy on the Risk of Infections and Death after Acute Stroke – A Historical Cohort Study

BackgroundInfections are a frequent cause for prolonged hospitalization and increased mortality after stroke. Recent studies revealed a stroke-induced depression of the peripheral immune system associated with an increased susceptibility for infections. In a mice model for stroke, this immunosuppressive effect was reversible after beta-blocker administration. The aim of our study was to investigate the effect of beta-blocker therapy on the risk of infections and death after stroke in humans.Methods625 consecutive patients with ischemic or hemorrhagic stroke, admitted to a university hospital stroke unit, were included in this historical cohort study. The effect of beta-blocker therapy on post-stroke pneumonia, urinary tract infections and death was investigated using multivariable Poisson and Cox regression models.Results553 (88.3%) patients were admitted with ischemic stroke, the remaining 72 (11.7%) had a hemorrhagic stroke. Median baseline NIHSS was 8 (IQR 5–16) points. 301 (48.2%) patients received beta-blocker therapy. There was no difference in the risk of post-stroke pneumonia between patients with and without beta-blocker therapy (Rate Ratio = 1.00, 95%CI 0.77–1.30, p = 0.995). Patients with beta-blocker therapy showed a decreased risk for urinary tract infections (RR = 0.65, 95%CI 0.43–0.98, p = 0.040). 7-days mortality did not differ between groups (Hazard Ratio = 1.36, 95%CI 0.65–2.77, p = 0.425), while patients with beta-blocker therapy showed a higher 30-days mortality (HR = 1.93, 95%CI 1.20–3.10, p = 0.006).ConclusionsBeta-blocker therapy did not reduce the risk for post-stroke pneumonia, but significantly reduced the risk for urinary tract infections. Different immune mechanisms underlying both diseases might explain these findings that need to be confirmed in future studies.     

Cytokines in chronic heart failure: possible interaction in the neurohormonal and the cytokine system at the cAMP level?

In recent years, the pathophysiological concept of chronic heart failure (CHF) has changed from an isolated hemodynamic view to a more complex concept involving neuroendocrine and inflammatory pathways. New therapeutic strategies, such as beta-blocker therapy, are based on these new concepts and provide clinical evidence for a clinical benefit in patients with CHF. The survival benefit of beta-blocker therapy in CHF has been related to neurohumoral regulation. Thus, evidence evolved showing that following beta-blocker therapy cytokine levels in CHF patients are altered. We have shown that the levels of soluble TNF receptor type 2 correlated well with cAMP in leukocytes. Data from clinical studies in adult and infant CHF patients have demonstrated that beta-blocker therapy is accompanied by altered cytokine, cytokine antagonist, and/or soluble cytokine receptor levels. These alterations may result from a dysregulated interaction of beta-adrenergic pathways and the cytokine system, and are possibly related to cAMP-dependent regulation of the release or shedding of these mediators.     

De oudere patiënt met hartfalen en de rol van bètablokkers bij de behandeling

Tijdschrift voor Gerontologie en Geriatrie - In this article different aspects of chronic heart failure in old age are described. We mainly focus on the place of beta-blocker therapy in chronic...     

A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure

Beta-adrenergic receptor (betaAR) blockade is a standard therapy for cardiac failure and ischemia. G protein-coupled receptor kinases (GRKs) desensitize betaARs, suggesting that genetic GRK variants might modify outcomes in these syndromes. Re-sequencing of GRK2 and GRK5 revealed a nonsynonymous polymorphism of GRK5, common in African Americans, in which leucine is substituted for glutamine at position 41. GRK5-Leu41 uncoupled isoproterenol-stimulated responses more effectively than did GRK5-Gln41 in transfected cells and transgenic mice, and, like pharmacological betaAR blockade, GRK5-Leu41 protected against experimental catecholamine-induced cardiomyopathy. Human association studies showed a pharmacogenomic interaction between GRK5-Leu41 and beta-blocker treatment, in which the presence of the GRK5-Leu41 polymorphism was associated with decreased mortality in African Americans with heart failure or cardiac ischemia. In 375 prospectively followed African-American subjects with heart failure, GRK5-Leu41 protected against death or cardiac transplantation. Enhanced betaAR desensitization of excessive catecholamine signaling by GRK5-Leu41 provides a 'genetic beta-blockade' that improves survival in African Americans with heart failure, suggesting a reason for conflicting results of beta-blocker clinical trials in this population.     

An interdisciplinary approach to the treatment of a hyperfunctional voice disorder

The purpose of this article is to describe the treatment of a 45-year-old male with a hyperfunctional voice disorder by a biofeedback therapist and a speech-language pathologist. The interdisciplinary approach to the treatment of this voice disorder involved the combined use of traditional voice therapy techniques and EMG biofeedback procedures together with cognitive behavioral therapy. Voice therapy was facilitated through the use of a computer-based, speech-monitoring system. The remediation of this voice disorder was attributed to the collaborative efforts of two professionals representing diverse professional training and treatment protocols. The results showed reductions in muscle activity in the infrahyoid and laryngeal areas as well as improved use of proper breathing and voicing onset behaviors. Follow-up at 10 and 15 months posttreatment intervals indicated that the client had retained all target voice skills and the tension reduction/biofeedback skills. Results suggest that interdisciplinary, collaborative efforts using biofeedback and voice therapy can prove beneficial in the treatment of hyperfunctional voice disorders.Note: Neither author has been compensated in any way for the use of the CAFET System nor does either have any financial interest in the company.     

The Role of Stem Cells in the Treatment of Cerebral Palsy: a Review

Cerebral palsy (CP) is a neuromuscular disease due to injury in the infant’s brain. The CP disorder causes many neurologic dysfunctions in the patient. Various treatment methods have been used for the management of CP disorder. However, there has been no absolute cure for this condition. Furthermore, some of the procedures which are currently used for relief of symptoms in CP cause discomfort or side effects in the patient. Recently, stem cell therapy has attracted a huge interest as a new therapeutic method for treatment of CP. Several investigations in animal and human with CP have demonstrated positive potential of stem cell transplantation for the treatment of CP disorder. The ultimate goal of this therapeutic method is to harness the regenerative capacity of the stem cells causing a formation of new tissues to replace the damaged tissue. During the recent years, there have been many investigations on stem cell therapy. However, there are still many unclear issues regarding this method and high effort is needed to create a technology as a perfect treatment. This review will discuss the scientific background of stem cell therapy for cerebral palsy including evidences from current clinical trials.     

Leucine-induced hypoglycemia in a family: effect of diphenylhydantoin, oxprenolol, and diazoxide

The present report describes a mother and 2 children with leucine-induced hypoglycemia (LIH). Hypoglycemic episodes following high-protein meals first appeared at age 4-7 months. Leucine-stimulation tests triggered marked hyperinsulinism and hypoglycemia in the children and a milder but abnormal response in the mother. To evaluate the therapeutic effects and to study the mechanism of hyperinsulinism in LIH, the leucine test was repeated under treatment with diphenylhydantoin, oxprenolol (a beta-blocker), and diazoxide. Diazoxide abolished hyperinsulinism; diphenylhydantoin did not affect the response to leucine; and oxprenolol, tested in the mother only, increased hyperinsulinism and hypoglycemia. Our results indicate that LIH is an autosomal dominant disorder; LIH may persist into adulthood with milder clinical symptoms and chemical response to leucine; diazoxide is the treatment of choice in LIH. Considering the effects of the three agents on stimulated release of insulin, it is concluded that leucine triggers hyperinsulinism by a mechanism different from that of glucose and beta-adrenergic receptors.     

Systematic Review of the Efficacy of Cognitive-Behavior Therapy Related Treatments for Victims of Natural Disasters: A Worldwide Problem

Natural disasters can have devastating consequences. Each year, about 225 million people are victims of natural disasters worldwide, and up to 13,5 million of these people can develop post-traumatic stress disorder (PTSD) in the first or second year following the disaster. Cognitive-behavior therapy (CBT) is the first-choice treatment for this disorder. In order to evaluate the efficacy of psychotherapeutic treatment based on cognitive-behavior therapy for people who developed post traumatic stress disorder after natural disasters we conducted a systematic search of published studies. We used the terms reported below in the electronic databases ISI Web of Science, PsycINFO, PubMed, PILOTS and Scopus with no restrictions of language or publication date. Articles that described randomized controlled, non-randomized controlled and non controlled studies on the efficacy of cognitive-behavior therapy for individuals diagnosed with post-traumatic stress disorder after exposure to a natural disaster were eligible for inclusion. The studies were required to use a standardized measure of effectiveness before and after the intervention and have a group of patients who had used cognitive-behavior therapy as the only intervention. Our search identified 820 studies, and 11 were selected for this review. These 11 studies involved 742 subjects, 10 related to earthquakes and 1 to a hurricane. The cognitive-behavior therapy techniques used were various: 7 studies used exposure therapy, 2 studies used problem solving, and the only 2 studies with adolescents used techniques including reconstructions and reprocessing of the traumatic experience. As limitations, the search involved only five electronic databases, no experts in the field were consulted, and the heterogeneity of the findings made it impossible to perform a meta-analysis. The results suggest the efficacy of cognitive-behavior therapy, particularly exposure techniques, for the treatment of post-traumatic stress disorder after earthquakes. However, further studies with stronger methodologies, i.e. randomized-control trials and non-randomized controlled trials, are needed.     

beta受体阻断药在心力衰竭合并房颤治疗中的再评价

β肾上腺素受体阻断药被认定为心力衰竭治疗领域的里程碑,在心力衰竭指南中,β肾上腺素受体阻断药为IA类推荐。但针对慢性心力衰竭的经典、大型RCT临床试验中,房颤患者所占比率不高。新近对于心力衰竭合并房颤患者应用β肾上腺素受体阻断剂的死亡率和住院率进行Meta-分析示:β肾上腺素受体拮抗剂未见有更多临床获益(即死亡率和住院率减低水平无统计学意义)。本文就心力衰竭定义、心力衰竭时交感神经系统激活、作用于交感神经系统的β肾上腺素受体阻断药药理作用及分类、β肾上腺素受体阻断药在心力衰竭并发房颤治疗中应用地位、心力衰竭并发房颤患者应用β肾上腺素受体阻断药存在的争议及其原因分析进行简要综述。     

Significance of immune response to enzyme-replacement therapy for patients with a lysosomal storage disorder

Lysosomal storage disorders are collectively important because they cause significant morbidity and mortality. Patients can present with severe symptoms that include somatic tissue and bone pathology, developmental delay and neurological impairment. Enzyme-replacement therapy has been developed as a treatment strategy for patients with a lysosomal storage disorder, and for many of these disorders this treatment is either in clinical trial or clinical practice. One major complication arising from enzyme infusion into patients with a lysosomal storage disorder is an immune response to the replacement protein. From clinical trials, it is clear that there is considerable variability in the level of immune response to enzyme-replacement therapy, dependent upon the replacement protein being infused and the individual patient. Hypersensitivity reactions, neutralizing antibodies to the replacement protein and altered enzyme targeting or turnover are potential concerns for patients exhibiting an immune response to enzyme-replacement therapy. The relative occurrence and significance of these issues have been appraised.     

Misdiagnosis and exacerbation of unusual obsessive-compulsive disorder presentation with risperidone and clozapine in an adolescent girl - A case report

Obsessive-compulsive disorder (OCD) is a heterogenous disorder with different clinical presentations. The most common symptoms are those that involve contamination, possible harm, ordering/symmetry, aggressive/sexual/religious concerns and hoarding. A variety of less common symptoms have been described. Unusual OCD symptoms may lead to misdiagnosis, inappropriate treatment with possible serious side effects. In this report we present a case of an adolescent girl in which unusual OCD presentation and symptoms were misinterpreted to represent psychosis and exacerbation of OCD symptoms with risperidone and clozapine treatment. We discuss the possible pathophysiological mechanisms of OCD symptom exacerbation, clinical implications, and successful management of this case, with fluvoxamine therapy. This case may represent the first report of musical obsessions successfully managed with fluvoxamine therapy.     

Salient components of a comprehensive service for eating disorders

Eating disorders are challenging and difficult to treat, because of the necessity of a multidisciplinary treatment team for effective outcomes and the high mortality rate of anorexia nervosa. An adequate initial assessment and evaluation requires a psychiatric assessment, a medical history and medical examination, a social history and an interview of family members or collateral informants. A comprehensive eating disorder treatment team includes a psychiatrist coordinating the treatment and appropriate medical physician specialists, nutritionists, and psychotherapists. An adequate outpatient eating disorder clinic needs to provide individual psychotherapy with cognitive behavioral techniques specific for anorexia nervosa and bulimia nervosa, family therapy, pharmacological treatment and the resources to obtain appropriate laboratory tests. Eating disorder patients requiring inpatient care are best treated in a specialized eating disorder inpatient unit. A cognitive behavioral framework is most useful for the overall unit milieu. Medical management and nutritional rehabilitation are the primary goals for inpatient treatment. Various group therapies can cover common core eating disorder psychopathology problems and dialectical behavior therapy groups can be useful for managing emotional dysregulation. Residential, partial hospitalization and day treatment programs are useful for transitioning patients from an inpatient program or for patients needing some monitoring. In these programs, at least one structured meal is advisable as well as nutritional counseling, group therapy or individual counseling sessions. Group therapies usually address issues such as social skills training, social anxiety, body image distortion or maturity fears. Unfortunately there is s paucity of evidence based randomized control trials to recommend the salient components for a comprehensive service for eating disorders. Experienced eating disorder clinicians have come to the conclusion that a multidisciplinary team approach provides the most effective treatment.     

Ultra-short acting beta-blockers: a proposal for the treatment of the critically ill patient

Beta-blockade is of proven value in the therapy of acute myocardial infarction but, unfortunately, may produce cardiac failure by removal of needed sympathetic support. The long duration of action of available blockers (hours) makes reversal of failure a complicated problem and precludes rapid modification of therapy to match changing autonomic conditions. To improve the safety and efficacy of beta-blockade in this setting we have developed the concept of ultra-short beta-blockade and have identified a novel beta-blocker (ASL-8052) which possesses a duration of action less than 15 minutes. This compound is cardioselective and possesses efficacy in an animal model of acute myocardial infarction. It, therefore, appears to be suitable for rapid attainment of controlled levels of beta-blockade via intravenous infusion and rapid recovery from beta-blockade if required by the clinical situation. The compound should, therefore, be useful for safe therapy in critically ill cardiac patients.     

Detection of gynecological cancer; use of fluorescence microscopy to show nucleic acids in malignant growth

Vitamin D resistant rickets is not a rare disorder. Increased awareness of this metabolic disorder during the examination of children with bowed legs, even infants receiving normal supplements of vitamin D, may lead to diagnosis oftener. Ten previously unrecorded cases of this disorder are included within this report. Three of the patients had associated congenital anomalies which also required treatment. Treatment of the vitamin D resistant rickets consists of the oral administration of large doses of vitamin D. Careful observation of patients during vitamin D therapy to prevent overdosage and resultant hypercalcemia is of utmost importance. Surgical correction of the bony deformities is rarely necessary. The cause of vitamin D resistant rickets is thought to be a defect of renal tubular mechanisms.     

VITAMIN D RESISTANT RICKETS

Vitamin D resistant rickets is not a rare disorder. Increased awareness of this metabolic disorder during the examination of children with bowed legs, even infants receiving normal supplements of vitamin D, may lead to diagnosis oftener. Ten previously unrecorded cases of this disorder are included within this report. Three of the patients had associated congenital anomalies which also required treatment. Treatment of the vitamin D resistant rickets consists of the oral administration of large doses of vitamin D. Careful observation of patients during vitamin D therapy to prevent overdosage and resultant hypercalcemia is of utmost importance.Surgical correction of the bony deformities is rarely necessary.The cause of vitamin D resistant rickets is thought to be a defect of renal tubular mechanisms.     

Electroconvulsive therapy for manic state with mixed and psychotic features in a teenager with bipolar disorder and comorbid episodic obsessive–compulsive disorder: a case report

Background

Comorbidity of bipolar disorder and obsessive–compulsive disorder is common in adolescence. Obsessive–compulsive disorder symptoms may be episodic and secondary to alterations in mood, and display specific features. Management of pediatric bipolar disorder-obsessive–compulsive disorder is challenging, as pharmacotherapy of obsessive–compulsive disorder may induce or exacerbate manic episodes and there is limited evidence of treatment efficacy. Electroconvulsive therapy is sparsely used in children and adolescents, but is documented to be a safe and efficacious intervention in adults with bipolar disorder. In view of the severity of symptoms in juvenile mania, studies on treatment strategies are warranted. We report a case of an adolescent with bipolar disorder-obsessive–compulsive disorder who was successfully treated with electroconvulsive therapy during an episode of severe mania.

Case presentation

A 16-year-old girl of Middle East origin first presented to us with depressed mood, irritability, and increased obsessive–compulsive disorder symptoms, which were initially interpreted in the context of acute stress secondary to migration. She had been diagnosed with bipolar disorder and obsessive–compulsive disorder in her previous home country, but had difficulties in accounting for earlier psychiatric history. During hospitalization her mood switched to a manic state with mixed and psychotic features, at times showing aggression toward others. Interruption in her lithium treatment for a short period and possibly the introduction of an atypical antipsychotic could in part have been triggering factors. After 8 weeks of in-patient care and psychotropic drug trials, electroconvulsive therapy was initiated and administered every second or third day for 4 weeks, with marked positive response. No apparent side effects were reported.

Conclusions

This case demonstrates the need for a detailed medical history, taking special note of periodicity and character of obsessive–compulsive disorder symptoms, in adolescents with mood disorders. When treating culturally diverse patients, extra consideration should be taken. Special concerns in the pharmacological treatment to avoid the patient’s condition from worsening must be addressed, including giving priority to mood stabilization before obsessive–compulsive disorder symptoms. There are potential benefits in considering electroconvulsive therapy in young patients with severe mania where first-line treatment options have failed.

     

A retrospective,follow-up study of biofeedback-assisted relaxation therapy in patients with posttraumatic headache

Although biofeedback in the treatment of migraine and tension-type headache has been widely researched, there is little research examining biofeedback therapy in posttraumatic headache (PTH). In this retrospective study, 40 subjects with PTH who had received biofeedback-assisted relaxation at our headache clinic were questioned at least 3 months following the completion of therapy. Subjects were queried about improvements in headache, increases in ability to relax and cope with pain, and overall benefits, lasting effectiveness, and continued use of biofeedback in daily life. Results indicate 53% reported at least moderate improvement in headaches; 80% reported at least moderate improvement in ability to relax and cope with pain; 93% found biofeedback helpful to some degree; 85% felt headache relief achieved through biofeedback had continued at least somewhat; and 95% stated they were continuing to use biofeedback skills in daily life. A correlation analysis revealed a negative relationship between response to biofeedback and increased chronicity of the disorder. In other words, the more chronic the disorder, the poorer the response to treatment. A stepwise regression analysis found that chronicity of the disorder and number of treatment sessions significantly affected response to treatment. Data suggest that biofeedback-assisted relaxation should at least be considered when planning treatment strategies for posttraumatic headache.We wish to express our appreciation to Sandra Tomlinson Becky Kinloch, and C. M. Bundrick for their assistance in this project.