Use Of Pharmacological Therapies Research Articles

Atrial Septal Defect: Spectrum of Care

Atrial septal defect (ASD) is a common congenital heart defect. Variability in management of this lesion exists among clinicians. A review of the literature reveals that there is lack of standard guidelines for the evaluation and management of patients with different types of ASDs. This survey-based study was conducted to test the uniformity of diagnostic and therapeutic approach to management of children with secundum, sinus venosus, and primum ASDs. Survey questionnaires were prepared to include questions regarding follow-up, diagnosis, and therapeutic intervention of different types and sizes of ASDs. Questions addressed follow-up visitations, type and frequency of investigative studies, pharmacological therapy, and choice of repair method. Surveys were sent out to all pediatric cardiology academic programs in the United States (n=48) and randomly selected international programs from Europe, Asia, and Australia (n=19). A total of 23 programs (34%) responded to the survey (15 from the United States and 8 internationally). A separate questionnaire was prepared for secundum, primum, and sinus venosus ASD. In each questionnaire, lesion types were subdivided into small, moderate, and large defect sizes to address differences of management approaches to each defect type and size. Results indicate that in secundum ASD, most participants use size of the defect and/or evidence of right-sided volume overload as criteria for defining small, moderate, and large defects. Frequency of follow-up does not vary with the type of lesion but is more frequent with larger defects. Most participants see patients with small defects at intervals of 6 months to 1 year and those with large defects at 3- to 6-month intervals. Age of patient and presence of symptoms determined the frequency of follow-up across all defects. Echocardiography was the most frequently used investigative modality in all defect sizes and types during follow-up visits (used by >80% for follow-up), followed by electrocardiography (ECG). There is a striking preference for the use of pharmacological therapy in primum ASD compared with secundum and sinus venosus ASD. The timing of repair was mainly dependent on patient age and symptomatology in different defects, with the presence of associated anomalies contributing to that in primum and sinus venosus ASD. Most participants use percutaneous approach to close secundum ASD (either as a first choice or as one of two choices depending on the presence of certain features). Before repair, participants use MRI or cardiac catheterization to fully evaluate a secundum ASD if it is large. These investigative modalities are not commonly used in primum and sinus venosus ASD. There is agreement on postoperative follow-up in different types of defects, with most participants continuing follow-up indefinitely, especially in larger defects.

Pharmacological Therapy for People with Alzheimer's Disease: The Balance of Clinical Effectiveness, Ethical Issues and Social and Healthcare Costs

The drive for evidence based practice and cost-effective use of pharmacological therapies has advantages, but can also be problematic. These difficulties are particularly challenging in the context of long-term conditions, such as Alzheimer's disease. The complexity of the illness, the variable and complex pattern of service use and the difficulty of conducting long term clinical trials are extremely difficult to factor into a meaningful cost effectiveness model. In Alzheimer's disease, the additional impact on caregivers as well as the person with dementia should be considered. In the current article we give a brief overview of the clinical effectiveness of cholinesterase inhibitors for the treatment of Alzheimer's disease, discuss in detail the NICE appraisal of these treatments in the UK as an example of an attempt at a standardised evaluation of cost-effectiveness and discuss a proposed way forward to achieve a unified and consistent approach to the assessment of cost-effectiveness for anti-dementia therapies.

Urticaria: current and future treatments

Urticaria is a common disorder with diverse clinical presentations. Correct recognition of the different clinical patterns promotes more effective treatment. Management involves treatment of any identifiable external causes, including infection, avoidance of drug, food and physical triggers and the appropriate use of pharmacological therapies. These can be divided into first-, second- and third-line approaches. The choice of treatment will be influenced by many factors, including drug licensing, safety, pattern of disease, disease severity, pharmacoeconomic considerations and patient preference. H1 antihistamines are the mainstay of treatment of most patterns of urticaria and are effective in the majority of patients with mast cell-mediated disease. Second-generation antihistamines have a better therapeutic index and improved pharmacodynamic properties compared with older ‘classic’ antihistamines and should be prescribed preferentially for chronic urticaria. Patients who are unresponsive to H1 antihistami...

Differences in presentation and management of Stable Angina from East to West in Europe: A comparison between Poland and the UK

Aims Variations in the resources, stability and priorities of health care systems conceivably affect their capacity to implement health care reform and ensure an evidence based approach to health care. Such variation may partially account for differences in cardiovascular mortality rates between former communist states in Central Europe and Western European countries, but specific data on this subject is sparse. The aim of this study was to compare the presentation of stable angina to cardiology services in Poland vs. the United Kingdom, the management of the condition in relation to existing European guidelines and clinical outcome. Methods and results Data was collected as part of a prospective observational cohort study of stable angina in Europe. Information was recorded on referral patterns, clinical presentation and the use of pharmacological therapies, investigations, revascularisation and cardiovascular events during 1 year of follow up. A total of 571 patients with stable angina were enrolled in Poland and 319 in the UK. Patients presenting to cardiology services in Poland were less likely to be referred by a primary care physician, younger, and had more adverse clinical risk predictors at presentation. Non-invasive investigation and coronary angiography were performed less frequently in Poland, but waiting times for invasive assessment were shorter. European guidelines with regard to the use of evidence based secondary preventative medical therapy were applied widely by cardiologists in both countries. No differences were observed in rates of cardiovascular events. Conclusions The use of evidence based pharmacological therapy was equally high in both countries, but guidelines regarding investigation were less completely adhered to in Poland, where invasive assessment and subsequent management was prompt but only performed in a highly selected proportion of the population with stable angina.

Comprehensive, Integrative Management of Pain for Patients with Sickle-Cell Disease

The study was conducted to: (1) investigate both pharmacologic and complementary therapies used for pain management by caregivers of children with sickle cell disease (SCD), (2) investigate the prevalence and types of complementary therapies used for pain management by caregivers of children with SCD, and (3) explore caregivers' interests in using complementary therapies in the future. A cross-sectional, descriptive design was used. Sixty-three caregivers of children with SCD were asked to complete a questionnaire while they visited a SCD clinic. Chi-square tests were performed to compare demographic variables, examine use of pharmacologic therapies for pain management between age groups, and compare use of pharmacologic and complementary therapies. The most frequently used pain medications for children with SCD (mean age 9 years) were ibuprofen (37.5%), acetaminophen with codeine (32.1%), and acetaminophen with oxycodone (14.5%). More than 70% of 63 caregivers (mean age 33 years) were using some form of complementary therapies (3.67 +/- 2.95, range: 0-9) for their child. The most commonly used therapies were prayer, spiritual healing by others, massage, and relaxation. Complementary therapy use was significantly higher among caregivers of children who were taking two or more analgesics compared to children taking no analgesics or one analgesic (chi (2) = 3.954, p = 0.047). Although no difference was found in nonopioid analgesic use, there was significant difference in opioid analgesic use (chi (2) = 14.736, p = 0.002) and total medication use (chi (2) = 11.025, p = 0.012) between children < or = 12 years and > or =13 years. Caregivers of children using greater numbers of conventional pain medications were more likely to be using complementary therapies as well. If offered in the future, many caregivers were willing to try various types of complementary therapies for pain management.

New Cholesterol Guidelines for Children?

For children and adolescents, comprehensive guidelines for the diagnosis and management of elevated cholesterol have been published once, by the National Cholesterol Education Program in 1992.1 Since then, substantial research on early atherosclerosis and in related clinical areas has been conducted; simultaneously, the obesity epidemic has added the metabolic syndrome and its related high-triglyceride/low–high-density lipoprotein (HDL) phenotype to the agenda of those interested in establishing a consensus approach to early cardiovascular disease prevention.2 Article p 1056 Before assuming that new knowledge and secular trends in risk factors demand substantial revision of cardiovascular health guidelines for children, we must first consider several valuable, often prescient aspects of the 1992 report. First is an emphasis on the importance of nutritional management over pharmacological management of elevated low-density lipoprotein (LDL) cholesterol, unless levels clearly associated with premature cardiovascular disease exist and children are sufficiently old that advanced atherosclerotic lesions may be presumed to be present. Two randomized trials of dietary intervention, the DISC (Dietary Intervention Study in Children) and STRIP (Special Turku coronary Risk factor Intervention Project for babies) studies, have shown that the diet recommended by the 1992 report is safe and mildly effective in lowering LDL cholesterol and thus can be implemented in population-based strategies of cardiovascular disease risk lowering.3,4 Furthermore, the PDAY (Pathobiological Determinants of Atherosclerosis in Youth) study has shown that advanced, irreversible atherosclerotic lesions (American Heart Association grades IV and V) are rarely present before 19 years of age and that the relationship of risk to atherosclerosis in late adolescence is with regard to reversible early lesion grades (American Heart Association grades I through III).5 A second and woefully underrecognized virtue of the 1992 report is the definition of risk strata for LDL cholesterol, with borderline values being 110 to 129 mg/dL and high …

Novel metabolic drugs for the management of type 2 diabetes

Diabetes is one of the major public healthcare concerns of the 21st century. Within the UK alone, the number of people diagnosed with type 2 diabetes has recently exceeded 2 million people,1 and there is believed to be another million people who remain undiagnosed. The picture is similar on a global scale with the number of people with diabetes in 2003 estimated at 194 million, a number expected to double by 2025.2 The increasing prevalence of diabetes, and more specifically, type 2 diabetes, makes it not only an increasing healthcare problem, but also a political and social challenge. Current therapeutic approaches to the treatment of type 2 diabetes advocate the initial use of lifestyle changes, including diet modification, adopting a regular exercise regimen, and alteration of alcohol consumption.3 If these prove to be ineffective at achieving or maintaining blood glucose target levels (defined here as glycated haemoglobin (HbA1c) levels of 6.5–7.5 per cent4), then current guidelines recommend the use of pharmacological therapy with oral metformin as the initial first-line agent.3,4 Failure to reach glycaemic targets with oral monotherapy leads to the use of additional drugs, such as the sulphonylureas and the thiazolidinediones (TZDs). The gradual failure of oral hypoglycaemic agents (OHAs) to keep patients’ glucose levels at target, due to the progressive nature of type 2 diabetes and the inexorable decline in beta cell function, means that many patients with type 2 diabetes eventually require insulin therapy3. The recognised importance of managing the growing number of people with type 2 diabetes has led to an explosion in the research and development of diabetes treatments. A number of these new treatments function by improving, either directly or indirectly, endogenous insulin secretion. The incretin hormone, glucagon like peptide-1 (GLP-1), stimulates glucose-dependent insulin release and inhibits glucagon release from pancreatic islet cells. In type 2 diabetes, GLP-1 secretion is decreased,5 and so agents that restore the action of GLP-1 may be effective future therapies. There are several GLP-1 analogues in development, the most advanced of which are exenatide, D I S E A S E M A N A G E M E N T

Nonpharmacological Interventions for Preschoolers With ADHD

The past decade witnessed an increased use of stimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD) in preschool children. However, the reluctance of parents of preschoolers to place their young children on stimulants ( S. H. Kollins, 2004) coupled with the paucity of information regarding the long-term effects of stimulants in preschoolers makes the development and testing of nonpharmacological treatments for preschoolers with ADHD a major public health priority. This article addresses this issue. First, we highlight issues relating to the existence of ADHD in preschoolers as a clinically significant condition and the need for effective treatment. Second, we examine issues related to the use of pharmacological therapies in this age group in terms of efficacy, side effects, and acceptability. Third, we discuss existing nonpharmacological interventions for preschoolers and highlight the potential value of parent training in particular. Finally, we introduce one candidate intervention, the New Forest Parenting Package, and present initial evidence for its clinical value as well as data on potential barriers and limitations.

DECOPI (DEsobstruction COronaire en Post-Infarctus): a randomized multi-centre trial of occluded artery angioplasty after acute myocardial infarction

To determine whether late recanalization of an occluded infarct artery after acute myocardial infarction is beneficial. Two hundred and twelve patients with a first Q-wave myocardial infarction (MI) and an occluded infarct vessel were enrolled. After coronary and left ventricular contrast angiography, patients were randomized to percutaneous revascularization (PTCA, n=109), carried out 2-15 days after symptom onset or medical therapy (n=103). The primary endpoint was a composite of cardiac death, non-fatal MI, or ventricular tachyarrhythmia. The majority had single-vessel disease and less than one-third had involvement of the left anterior descending artery. The use of pharmacological therapy was high in both groups. At six months, left ventricular ejection fraction was 5% higher in the invasive compared with the medical group (P=0.013) and more patients had a patent artery (82.8% vs 34.2%, P<0.0001). Restenosis was seen in 49.4% of patients in the PTCA group. At a mean of 34 months of follow-up, the occurrence of the primary endpoint was similar in the medical and PTCA groups (8.7% vs 7.3% respectively, P=0.68), but the overall costs were higher for PTCA. The secondary endpoint combining the primary endpoint with admission for heart failure was also similar between groups (12.6% vs 10.1% in the medical and PTCA groups, respectively, P=0.56). Systematic late PTCA of the infarct vessel was associated with a higher left ventricular ejection fraction at six months, no difference in clinical outcomes, and higher costs than medical therapy. These results must be interpreted with caution given the small size and low risk of the population.

Pharmacologic treatment of hypertensive disorders during pregnancy.

Pregnancy complicated by hypertension is a common problem faced by clinicians. It can lead to substantial maternal and/or fetal/neonatal morbidity and mortality. There are a variety of medications that can be used during pregnancy either for treatment of significant chronic hypertension or in cases of acute severe hypertension. Most antihypertensive drugs have been shown to be safe for use in pregnancy. A variety of medications are available to treat more severe hypertension, although the use of pharmacologic therapy to treat mild chronic hypertension during pregnancy has not been supported in the literature. The data are more limited concerning drugs that would be used in the event of hypertensive emergencies or in an intensive care setting; however, in such a situation, maternal health and life become paramount and, despite lack of good studies, appropriate treatment should be rendered.

Epilepsy: major advances in treatment

1assessed the dose–response association of lamotrigine and TMS in 16 healthy male volunteers in a double-blind, randomised, placebo-controlled, three-way-crossover study. There was a correlation of lamotrigine dose with TMS response. There was also high interindividual variability in the correlation of serum concentration of lamotrigine and TMS response. This first description of a dose–response relationship between an AED and TMS in healthy volunteers is a significant achievement and suggests a role for TMS in the titration of lamotrigine and other AEDs in individual patients. Before this test could be used clinically, however, additional studies are needed in patients with epilepsy to prove that TMS is safe, to relate TMS responses with AED efficacy and tolerability, and to show that TMS is better than serum concentrations as a predictor of efficacy and tolerability. Depression is the most common psychiatric comorbidity in patients with epilepsy, is associated with diminished quality of life, and is a risk factor for suicide. But depression is underdiagnosed and undertreated, perhaps in part because clinicians might falsely assume that all is well in patients without active seizures. Attarian and colleagues 2 investigated the relation between seizure rates and depression in 143 patients with epilepsy from outpatient clinics. 11% of patients who were seizure free more than 6 months were depressed, which was nearly identical to the percentage of patients with active seizures who were depressed (10%). Furthermore, there was no relation between severity of depression and the monthly seizure rate. This study, which needs to be replicated in other settings, suggests that epilepsy— but not current seizure frequency—is a risk factor for depression and that seizure frequency does not predict severity of depression. In light of the significant psychosocial morbidity and risk of suicide associated with depression in patients with epilepsy, this study should prompt clinicians to assess all patients for depression irrespective of degree of seizure control. Epilepsy syndromes are diagnosed on the basis of two or more unprovoked seizures together with other characteristic clinical and demographic features. A possible exception is Panayiotopoulos syndrome, which affects up to one in eight young children and typically manifests as a single, long-lasting seizure with autonomic features. Lada and colleagues 3 studied the clinical features, EEG findings, and prognosis in 43 patients with Panayiotopoulos syndrome who were followed up for up to 17 years (mean 5·6 years). Two-thirds of the patients were female, and the mean age at first seizure was 5 years. Nausea and emesis with retained consciousness heralded seizure onset in more than threequarters of patients. Other characteristic ictal features were confusion or impaired consciousness as the seizure progressed (100%), lateral gaze deviation (56%), and additional autonomic signs—including urinary incontinence, pallor, perioral cyanosis, and hypersalivation. In 36 patients (84%), seizures occurred in association with sleep or near arousal from sleep. Seizures in nearly half the patients lasted for over 30 min, many ended in generalised or half-body convulsions. Most children were treated with AEDs, doses of which were tapered off. Over half the patients experienced only one seizure; others had two or three. EEGs were normal in about a third of the patients and showed epileptiform abnormalities in the others. Six children (14%) were misdiagnosed as having encephalitis, head injury, or gastroenteritis. This study shows for the first time that interictal EEGs are commonly normal. Paediatricians, family physicians, and neurologists should all consider this syndrome when making the differential diagnosis of children newly presenting with seizures, especially prolonged, sleep-related seizures with vomiting at onset. One in three patients with epilepsy will not achieve seizure freedom from available AEDs, and thereby become potential candidates for resective brain surgery. Yet for many patients, referral for presurgical assessment is delayed for years after response to antiseizure therapy is established. Perhaps one factor is the lack of certainty about long-term prognosis. Clinicians are generally aware of the high probability of shortterm seizure freedom from resection for epilepsy, but what about long-term results? Yoon and colleagues 4 assessed long-term seizure outcome in 175 patients at one centre who had lobectomy from 1972 to 1992 and who were seizure-free during the first year after surgery. Over a mean follow-up of 8·4 years, nearly two-thirds of patients were seizure free. After 10 years, the likelihood of continued seizure freedom was 56%. Long duration of preoperative epilepsy and normal pathology were associated with increased risk of relapse. Of those patients whose seizures relapsed, half had at most one seizure per year. These data should reassure clinicians about the excellent long-term prognosis from resection, especially when surgery is compared to the primary alternative—continued use of pharmacological therapy in patients who have not responded to the therapy.

Neural control of the urethra and development of pharmacotherapy for stress urinary incontinence.

This review discusses the control of the urethra by the central nervous system, emphasizing the importance of nervous system control and the role of serotonin and noradrenaline in storage, micturition and sphincter reflexes. The concept of pharmacological neuromodulation and the use of pharmacological therapy as first-line therapy for stress urinary incontinence (SUI) is presented. Coordination between the urinary bladder and urethra is mediated by many reflex pathways organized in the brain and spinal cord. During bladder filling, activation of mechanoreceptor afferent nerves in the bladder wall triggers firing in the cholinergic efferent pathways to the external urethral sphincter and in sympathetic adrenergic pathways to the urethral smooth muscle. These storage reflexes depend on interneuronal circuitry in the spinal cord and are modulated by descending pathways. It would therefore seem that neurotransmission in the central nervous system and periphery may be important in SUI, and moreover that pharmacological agents affecting these neurotransmitter pathways may be used to treat SUI. The central and peripheral mechanisms of action of duloxetine affect serotonin and noradrenaline neurotransmission in ways that may ameliorate the symptoms of SUI.

Statins and C-reactive protein: considering a novel marker of cardiovascular risk.

Landmark intervention trials have validated the importance of lipid control in reducing the incidence of coronary ischemic events, over a range of baseline lipid levels. With the release of the third iteration of the National Cholesterol Education Programs Adult Treatment Panel guidelines, there is renewed debate about the appropriate use of pharmacologic therapies in individual patients, especially in primary prevention. Markers of low-grade inflammation may capture the inflammatory aspect of atherosclerosis and may prove to be useful clinical predictors of excess coronary risk. C-reactive protein, an acute-phase reactant protein, appears to be one such promising measurement and may have important implications for the optimal targeting of statin therapy.

Pharmacological strategies to decrease transfusion requirements in patients undergoing surgery.

Surgical procedures are inevitably associated with bleeding. The amount of blood loss may vary widely between different surgical procedures and depends on surgical as well as non-surgical factors. Whereas adequate surgical haemostasis may suffice in most patients, pro-haemostatic pharmacological agents may be of additional benefit in patients with (diffuse) surgical bleeding or in patients with a specific underlying haemostatic defect. In general, surgical haemostasis and pharmacological therapies can be complementary in controlling blood loss. The use of pharmacological therapies to reduce blood loss and blood transfusions in surgery has historically been restricted to a few drugs. Antifibrinolytic agents (aprotinin, tranexamic acid and aminocaproic acid) have the best evidence supporting their use, especially in cardiac surgery, liver transplantation and some orthopaedic surgical procedures. Meta-analyses of randomised, controlled trials in cardiac patients have suggested a slight benefit of aprotinin, compared with the other antifibrinolytics. Desmopressin is the treatment of choice in patients with mild haemophilia A and von Willebrand disease. It has also been shown to be effective in patients undergoing cardiac surgery who received aspirin up to the time of operation. However, overall evidence does not support a beneficial effect of desmopressin in patients without pre-existing coagulopathy undergoing elective surgical procedures. Topical agents, such as fibrin sealants have been successfully used in a variety of surgical procedures. However, only very few controlled clinical trials have been performed and scientific evidence supporting their use is still limited. Novel drugs, like recombinant factor VIIa (eptacog alfa), are currently under clinical investigation. Recombinant factor VIIa has been introduced for the treatment of haemophilia patients with inhibitors, either in surgical or non-surgical situations. Preliminary data indicate that it may also be effective in surgical patients without pre-existing coagulation abnormalities. More clinical trials are warranted before definitive conclusions can be drawn about the safety and the exact role of this new drug in surgical patients. Only adequately powered and properly designed randomised, clinical trials will allow us to define the most effective and the safest pharmacological therapies for reducing blood loss and transfusion requirements in surgical patients. Future trials should also consider cost-effectiveness because of considerable differences in the costs of the available pro-haemostatic pharmacological agents.

Pharmacological therapy of osteoarthritis.

In 2000, both the American College of Rheumatology (ACR) and the European League of Associations of Rheumatology (EULAR) published recommendations for the use of pharmacological therapy in the treatment of patients with lower limb osteoarthritis. These recommendations are based on the level of evidence observed in systematic reviews and/or meta-analyses of published randomized controlled trials as well as expert opinion. Acetaminophen (paracetamol) is considered as first-line oral therapy for symptomatic lower limb osteoarthritis with mild to moderate pain because it is more efficacious than placebo and is generally considered to be safe and well tolerated. Data obtained in recent trials and the results of a meta-analysis, however, show that acetaminophen is not as efficacious as non-steroidal anti-inflammatory drugs (NSAIDs) for pain at rest and pain on motion. Furthermore, data from a recent epidemiological study suggest that use of high-dose acetaminophen (>2 g/day) may convey the same magnitude of increased risk for serious upper gastrointestinal adverse events as NSAIDs.NSAIDs have demonstrated efficacy superior to placebo in patients with osteoarthritis. The newer cyclo-oxygenase (COX)-2-specific inhibitors (coxibs) have comparable efficacy to traditional dual inhibitor NSAIDs and have demonstrated a better gastrointestinal safety profile. Thus, for patients who have severe pain and/or signs of inflammation or who have failed to respond to acetaminophen, the use of a coxib should be considered, especially if the patient is at increased risk for serious upper gastrointestinal adverse events from a traditional NSAID.Compounds different from pure analgesics and NSAIDs are also used for the management of patients with osteoarthritis. Recent clinical trials have demonstrated statistically significant efficacy of such compounds (e.g. chondroitin sulphate, diacerhein, glucosamine sulphate) with the following characteristics: (1) the effect size seems to be of slightly lower magnitude than that seen for NSAIDs; (2) the onset of action is delayed for approximately 4 to 6 weeks; and (3) the symptomatic effect is maintained after stopping the treatment for periods of 4 to 8 weeks.The methodology for evaluating the possible structure-modifying effect of drugs has dramatically improved during the past decade. Two agents have demonstrated a beneficial structural effect: glucosamine sulphate in osteoarthritis of the knee, and diacerhein in osteoarthritis of the hip. The clinical relevance of such an effect needs to be further evaluated in long-term outcome studies.

Clinical case-based approach to understanding intradialytic hypotension

The approach to end-stage renal disease (ESRD) patients who develop intradialytic hypotension (IDH) encompasses an understanding of the pathophysiology, appropriate dialysis prescription modification, application of newer pharmacologic therapies, and development of strategies for prevention. Patients should have a “minimal data set” as part of their predialysis assessment. This information is critical to prescription modifications that may help decrease the risk for IDH. Individuals at “high risk” for IDH should be kept to a “safe zone” for dialysis ultrafiltration (≥3% of body weight). Specific maneuvers that may decrease the risk for IDH include adjustment of the dialysate sodium or calcium concentration and dialysate temperature. The first priority for patients developing IDH should be the stabilization of the blood pressure and improvement in the patient's symptomology. Pharmacologic intervention should be considered for patients who require repeat interventions for IDH. “At-risk” patients with a strong cardiac history should undergo an assessment of their cardiovascular status if IDH episodes occur. The use of pharmacologic therapy, ie, midodrine, alone or in combination with prescription modification, can be helpful in decreasing interventions required for IDH. Noncompliance and high interdialytic weight gain in the setting of left ventricular hypertrophy (LVH) and diastolic dysfunction can increase the risk of IDH. Assessment of antihypertensive medications should be performed on a regular basis to determine the correct dosing schedule for patients with hypertension who develop IDH. Coronary flow reserve may be compromised in patients with LVH, adding to the risk for perfusion injury with low blood pressure. Increasing the dialysate calcium concentration may decrease the incidence of arrhythmogenicity in certain patients. Patients with low body temperature may benefit most from cool dialysate. Unit personnel should be aware of the potential link between hypotension and the increased relative risk for death in ESRD patients. Clinical training sessions on IDH risk recognition and appropriate treatment should be implemented within the dialysis unit. Because repeated bouts of IDH can be disruptive to the smooth efficiency of unit operations, attention to prevention as well as acute intervention of IDH is important. Preventive strategies can be developed in each unit to decrease the number of future IDH events. Considering the importance of hypotension in overall patient survival, attention to identifying the percentage of patients in each unit who experience IDH and/or who present with low blood pressure (systolic <110 mm Hg) should be tracked as a quality assurance initiative. © 2001 by the National Kidney Foundation, Inc.

Calming the plaque to delay intervention for 24 hours in acute coronary syndromes

One approach to management of patients with acute coronary syndromes involves use of pharmacologic therapy to passivate plaque for at least 24 hours before interventional procedures are undertaken. This approach is supported by the view that whatever subsequent treatment the patient receives will less likely be complicated. An important factor in revolutionizing treatment for acute coronary syndromes in recent years has been the introduction of potent new antithrombotic and antiplatelet pharmacologic therapies such as low-molecular-weight heparins and glycoprotein IIb/IIIa inhibitors. Incorporation of these newer agents into clinical practice, along with a better understanding of the pathophysiology underlying acute coronary syndromes, has contributed greatly to improved outcomes in these patients. Although the optimal methods for integrating the newer therapies remains to be determined, thus far, they have been shown to lower the risk of acute complications, as well as improve long-term results.

Observed patient compliance with a structured outpatient bladder retraining program

Objective: Our purpose was to determine patient compliance with a telephone-based retraining program. Study Design: This was a retrospective study of 123 women with urinary urgency or urge incontinence who were offered bladder retraining with facsimile machine submission of a retraining diary and weekly telephone feedback. Results: Completion was defined as having ≥4 follow-up sessions and ≥6 weeks of retraining. Seventy-one percent (87/123) began the retraining program; 63% (55/87) of them completed it, for an overall compliance rate of 45% (55/123). When we compared those who completed retraining with those who started but did not complete it, only concurrent use of pharmacologic therapy was significantly different (87% vs 53%, respectively; P < .001). This difference remained significant after we controlled for other independent variables, including urodynamic diagnosis and physician. Conclusions: A total of 55% of women to whom telephone-based bladder retraining was recommended either never started or were noncompliant with the treatment. Bladder retraining success in the “real world” may be substantially lower than that described in well-funded labor-intensive clinical trials. (Am J Obstet Gynecol 1999;181:1392-4.)

Why are we trying to reduce length of stay? Evaluation of the costs and benefits of reducing time in hospital must start from the objectives that govern change.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but life-threatening disease resulting from unresolved thromboembolic obstructions. Pulmonary endarterectomy (PEA) surgery is the gold-standard treatment as it is potentially curative; however, not all patients are deemed operable and up to one-third have persistent or recurrent CTEPH after the procedure. Pulmonary arterial hypertension (PAH) and CTEPH have similar clinical presentations and histopathological features, so agents shown to be effective in PAH have often been prescribed to patients with CTEPH in the absence of proven therapies. However, clinical evidence for this strategy is not compelling. A number of small uncontrolled trials have investigated endothelin receptor antagonists, prostacyclin analogues and phosphodiesterase type 5 inhibitors in CTEPH with mixed results, and a phase III study of the endothelin receptor antagonist bosentan met only one of its two co-primary end-points. Recently, however, the soluble guanylate cyclase stimulator, riociguat, was approved in the USA and Europe for the treatment of inoperable or persistent/recurrent CTEPH following positive results from the phase III CHEST study (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial). This article reviews the current evidence for the use of pharmacological therapies in CTEPH.

ミエロペルオキシダーゼに対する抗好中球細胞質抗体(MPO-ANCA)陽性の抗糸球体基底膜抗体(GBM)型腎炎の一例

A 68-year-old patient visited our hospital, because of progressive renal failure. Laboratory data were serum creatinine 13.3 mg/dl, BUN 74.3 mg/dl, AGBMA 134U, MPO-ANCA 37% and CIC 1.6 g/dl. Hemodialysis was performed on admission and renal biopsy was conducted. Though the histological findings showed fibrocellular crescents and global sclerosis in many glomeruli, renal function was gradually ameliorated by administration of prednisolone (40 mg/day) and cyclophosphamide (50 mg/day). After 3 weeks of therapy, hemodialysis was withdrawn temporarily. Because of the complication of pneumocystis carini, prednisolone and cyclophosphamide were discontinued, and maintenance hemodialysis was resumed. In spite of progressed histological findings, hemodialysis was withdrawn at least temporarily through the use of pharmacological therapy. Thus, the presence of ANCA may indicate a relatively good prognosis of AGBMA nephritis.