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Treatment patterns of isolated benign headache in US emergency departments.

STUDY OBJECTIVE: I sought to describe and analyze the treatment of a large representative sample of adult US emergency department patients with isolated primary headache. METHODS: Information on adult patients with an isolated diagnosis of migraine headache or unspecified headache was extracted from the 100.4 million ED visits represented by the 1998 National Hospital Ambulatory Medical Care Survey. Demographic and clinical information are presented with descriptive statistics. The treatment of migraine headache was assessed in light of Canadian and US practice parameters. RESULTS: The migraine headache and unspecified headache cohorts included 811,419 and 604,977 participants, respectively. The majority of patients were young, white, and female. Patients received a mean of 1.8 medications from a pharmacopoeia of 36 drugs. Most patients (84.8%) given a diagnosis of migraine headache received a parenteral agent. The most commonly used medications were meperidine (30.0%), ketorolac (21.4%), and prochlorperazine (16.7%). Adjunct antiemetics were commonly administered with parenteral opioids (89.8%). Promethazine and hydroxyzine, antiemetics without anti-headache effects, were used 6 times more commonly as adjuncts than the dopamine antagonists that have established anti-headache effects (ie, prochlorperazine, metoclopramide, droperidol; 78.0% versus 11.8%). The US and Canadian recommendations for the use of nonopioid abortive medications (dopamine-antagonist antiemetics, dihydroergotamine, and 5-hydroxytrypamine(1) [5-HT(1)] receptor agonists) are supported by strong evidence. However, parenterally treated patients with migraines received opioids as their only anti-headache medication more commonly than they received any of the aforementioned non-opioids in their regimen (45.7% versus 26.0%). Of all the opioid recipients, most (77%) did not receive any nonopioid abortive headache medication. Meperidine was the most commonly administered opioid (70%). CONCLUSION: Polypharmacy and a broad pharmacopoeia characterize the US ED treatment of isolated benign headache. Opioid use, particularly meperidine, exceeds that of recommended nonopioid abortive migraine medications.

Administration, Oral↗

Variations among emergency departments in the treatment of benign headache.

STUDY OBJECTIVE: The practice patterns of US emergency departments in the treatment of patients with isolated benign headache have been recently described. How treatment varies among EDs has not been reported. To assess institutional variability in the pharmacotherapy of patients with benign headache, we describe and analyze the practice patterns of 3 US EDs. METHODS: This health records survey included a cohort sample of consecutive adult patients aged 16 to 65 years treated with parenteral medication for isolated benign headache at 3 nonaffiliated US EDs: a large, group-model health maintenance organization, a tertiary-care academic center, and a rural community hospital. Patients who underwent a diagnostic search for intracranial pathology, who had any nonheadache secondary diagnosis, or who had coexistent trauma, fever (temperature of > or =38.0 degrees C [100.4 degrees F]), or known pregnancy were excluded from study analysis. Demographic, clinical, and pharmacotherapeutic variables were collected for each ED visit. Descriptive analyses were performed; comparisons were made with t tests. RESULTS: Of the 490 eligible patients treated during the 4-month study period, the mean age was 36.4 years, and 374 (76%) were women. During their 629 visits, 364 (58%) received a migraine diagnosis, and 258 (41%) received a nonspecific headache diagnosis. Polypharmacy was common: 515 (82%) received 2 or more medications, and 154 (25%) received 3 or more medications. Pharmacotherapy varied greatly among the EDs. Use of opioid agonists showed the widest variation (16% to 72%), although use of dihydroergotamine (5% to 16%), prochlorperazine (32% to 59%), and adjunct diphenhydramine with prochlorperazine (42% versus 88%) also varied. CONCLUSION: Great institutional variability exists among US EDs in the parenteral treatment of patients with isolated benign headache.

Adolescent↗

Problems of nutritional assessment in the community.

The present paper explores the problems associated with assessment of nutritional status in the community and reviews the literature related to this subject. The first problem is one of terminology, since a logical first step before assessment is screening, which identifies characteristics known to be associated with dietary or nutritional problems. Its purpose is to differentiate individuals who are at high nutritional risk or have poor nutritional status. There are certain factors which should alert the primary health care team to the fact that nutritional intake may be reduced and that risk of malnutrition is increased. These include disease condition, functional disabilities, inadequate or inappropriate food intake, poor dentition or difficulty swallowing, polypharmacy, alcoholism, depression, poor social circumstances or recent discharge from hospital. Patients suffering from these factors need to be identified so that screening becomes a routine part of their medical treatment. At-risk groups include the elderly, the chronically ill, those with cancer and neurological disorders, post-surgical patients and children with developmental disabilities. In the community, practice and community nurses see the majority of at-risk patients and should carry out screening. A number of screening tools have been developed for community use. Most are aimed at the elderly population, but there are others designed to assess nutritional risk in children with developmental disabilities and the general population. These are reviewed and problems of content and validity identified. Some problems associated with nutritional assessment are also reviewed.

Community Health Services↗

Hyperlipidemia therapy: can it prevent coronary atherosclerosis?

Improvements in diagnosis permit primary care physicians to identify lipid disorders. Until recently, most of the therapy for coronary artery disease was directed at the symptoms produced by the ischemic myocardium. As more studies reveal the close relationship between the presence of abnormal lipid levels and the prevalence and progression of coronary artery disease, physicians who care for coronary patients should pay closer attention to the possibility of preventing or attenuating progression of the disease. The development of effective drugs represents an initial phase in long-range resolution of the problem of progressive vascular disease. While dietary management is important, pragmatic considerations suggest that modification of serum lipids to ideal levels will require the use of polypharmacy.

Cholesterol↗

Gemfibrozil in combination with other drugs for severe hyperlipidemia. Preliminary study comprising four cases.

In this very early report, Dr Nash shares his insights into a newly developing approach to hyperlipidemia therapy. Four severely hyperlipidemic patients in whom maximum dietary therapy had proved ineffective showed a dramatic reduction in cholesterol and triglyceride levels when treated with multiple drugs, including gemfibrozil. These cases demonstrate that maximally effective polypharmacy can have striking results in selected patients. These provocative findings should encourage other investigators to verify or refute them.

Adult↗

Acute myocardial infarction. Treatment in the coronary care unit.

Management of the patient with acute myocardial infarction is in flux. In the current "reperfusion era," many patients receive intravenous thrombolytic therapy and aspirin before admission to the coronary care unit. Appropriate use of drugs limits expansion of the infarct and reduces mortality rates in patients with uncomplicated myocardial infarction. Percutaneous transluminal coronary angioplasty may be necessary in those who are not candidates for drug treatment or who show recurrent ischemia after thrombolysis, while cardiac transplantation may be the only hope for patients with multivessel disease who are in cardiogenic shock. The "cocktail era," in which polypharmacy is both acceptable and effective, will likely be the next stage in management of acute myocardial infarction.

Angioplasty, Balloon↗

Antipsychotic medication and length of stay at a psychiatric maximum-security unit in Norway (1987-2000).

The aim of this study was to evaluate psychopharmacological treatment and the length of stay (LOS) of patients with schizophrenia in a maximum-security psychiatric unit. Data were collected from the hospital files of 82 consecutively admitted patients with schizophrenia who were both admitted and discharged between the years 1987 and 2000. Psychotropic medication and LOS at the time of discharge were registered. Ninety-five per cent of the patients received antipsychotic medication. Zuclopenthixol was the most frequent medication, given to 43% of the patients. Antipsychotic polypharmacy was found in 20% of the cases. Twenty-seven per cent of the patients were medicated with doses above the recommended therapeutic dose range. During the study period, there was no change in the administration and number of psychotropics, but there was an increase in the dosage of antipsychotics. However, LOS was unchanged during the same time. This supports other findings, which suggest that there is no clinical benefit of higher antipsychotic dosage. It is suggested that an optimized medication practice could yield beneficiary effects, not only for schizophrenic symptoms, but also for violence in schizophrenic patients.

Adult↗

Empirical evidence for the use of lithium and anticonvulsants in children with psychiatric disorders.

BACKGROUND: The use of psychotropic medications-in particular, mood stabilizers--in youths with psychiatric illness has grown. There are trends toward polypharmacy and the increased use of newer mood stabilizers in youths with psychiatric illness despite a paucity of studies examining the short- and long-term efficacy and safety of these agents in the pediatric population. METHOD: PubMed was used to identify peer-reviewed publications from the past 30 years (January 1975 to August 2005) studying lithium and anticonvulsants in youths with psychiatric illness. RESULTS: Evidence supporting the use of lithium and valproate in the treatment of juvenile bipolar disorder and reactive aggression has grown. Evidence for the use of other anticonvulsants in youths with psychiatric illness is sparse. Side effects from lithium and anticonvulsants are typically mild to moderate. Data are accumulating in regard to the longer-term safety of lithium and DVPX in the juvenile psychiatric population. Although data in regard to the newer anticonvulsants are limited, they may have more desirable side-effect profiles. CONCLUSION: Double-blind, placebo-controlled trials of lithium and anticonvulsants are greatly needed as clinical use of these agents has risen without sufficient evidence supporting their efficacy in the pediatric population.

Amines↗

Trends in antipsychotic prescribing in schizophrenia in Auckland.

OBJECTIVE: This study describes antipsychotic prescribing practices for outpatients with schizophrenia over a 3 year period in two large mental health catchment areas of Auckland. METHODS: All community files were reviewed at three time points. Patient characteristics, diagnosis and antipsychotic treatment information were recorded and analysed. RESULTS: Over the three time periods, the number of outpatients with a diagnosis of schizophrenia or schizoaffective disorder was stable. There was a marked change in the type of antipsychotic prescribed, with an 18.6% increase in atypical antipsychotics and a decrease in both intramuscular and oral typical antipsychotics. Clozapine was the most commonly prescribed antipsychotic in 2003 (35%). Despite the fact that polypharmacy was relatively low (14.6% in 2003), those receiving more than one antipsychotic had a greater likelihood of being prescribed a higher total daily dose. CONCLUSIONS: This study describes a change in antipsychotic prescribing towards recommended practice guidelines for the treatment of schizophrenia over a 3 year period.

Administration, Oral↗

The off-label use of clozapine in adolescents with bipolar disorder, intermittent explosive disorder, or posttraumatic stress disorder.

OBJECTIVE: There are limited data in the literature regarding clozapine use in adolescents with diagnoses other than schizophrenia. This report describes the use of clozapine in adolescents with diagnoses of bipolar disorder, intermittent explosive disorder (IED), and posttraumatic stress disorder (PTSD). METHODS: A chart review of 39 adolescents treated with clozapine at two residential facilities was undertaken. Data extraction included demography, illness variables, medication information, and clinical outcomes. Categorical outcomes were analyzed using contingency statistics, and continuous variables were analyzed using a paired t test. RESULTS: The cohort included 26 females and 13 males with a mean age of 14 years. Clozapine was titrated slowly, and the mean daily dose was 102 mg. The diagnoses included bipolar disorder (n = 7), IED (n = 9), and PTSD (n = 19). There were significant reductions in polypharmacy once the clozapine dosage was stabilized. Prior to clozapine treatment, nearly 70% of the subjects were receiving either mood-stabilizing or antidepressant agents in combination with the previous antipsychotic drug. Once the clozapine dosage was stabilized, only 24% of the subjects required concomitant mood stabilizers (p < 0.001), and only 21% of the subjects required concomitant antidepressants (p < 0.001). Anxiolytic medication use was also significantly reduced during clozapine treatment. Most patients were discharged to a less restrictive setting. Eight subjects discontinued clozapine due to agranulocytosis (n = 1), neutropenia (n = 2), excessive weight gain (n = 2), or not requiring it long term (n = 1), and data were unavailable in 2 subjects. Significant weight gain (5% or greater change from baseline) was noted in 20 subjects. CONCLUSIONS: Clozapine, in relatively modest doses, appears to have clinical benefits for adolescent with bipolar disorder, IED, and PTSD. There is no labeled indication for clozapine use in these disorders. Clozapine is also associated with serious side effects in subsets of individuals. Therefore, a very careful evaluation of the risk-to-benefit ratio in each individual subject being considered for clozapine is highly recommended.

Adolescent↗

Psychotropic prescription practices in child psychiatric inpatients 9 years old and younger.

OBJECTIVE: We set out to examine psychotropic prescribing patterns among inner city children on public assistance admitted to a university-based inpatient service. METHODS: A chart review of children 9 years old and younger admitted between 1998 and 2001 recorded demographic variables, diagnoses, and admission and discharge medications. RESULTS: The sample (N = 301) was 78% male, 66% African American, and averaged 7.2 years of age. Of this sample, 85% had a behavior disorder on admission and discharge; 51.8% of the patients were medicated on admission, 78.7% on discharge. Approximately 25% received polypharmacy on either admission or discharge. Stimulants were the most widely used psychotropic (38.2% on admission, 60.5% on discharge). Other medications prescribed at admission versus discharge were alpha-2 agonists (9.3% vs. 9%), atypical antipsychotics (9% vs. 12%), antidepressants (8.3% vs. 15.9%), and mood stabilizers (5.6% vs. 2.3%). CONCLUSIONS: Among inner city children, pharmacotherapy is more prevalent in an inpatient unit compared with the community standard. Community physicians prescribed more mood stabilizers; the academic faculty used more stimulants, atypical antipsychotics, and antidepressants. Predictors of pharmacotherapy in the community such as age, sex, race, and a behavior disorder shifted at discharge to include only length of stay and a behavior disorder diagnosis. Further research is needed to clarify whether nonadherence, treatment failure, and social factors account for lower medication utilization in the community.

Child↗

Concomitant use of atomoxetine and OROS-methylphenidate in a 10-year-old child suffering from attention-deficit/hyperactivity disorder with comorbid bipolar disorder and Tourette syndrome.

Atomoxetine and OROS methylphenidate were successfully used concomitantly in a 10-year-old boy suffering from attention-deficit/hyperactivity disorder (ADHD) with comorbid bipolar disorder and Tourette syndrome (TS). The child received valproic acid, clonidine, and ziprasidone concurrently. Because possible side effects of pharmacological treatment for one diagnosis may exacerbate a comorbid condition, contingent management strategies, when using polypharmacy, are mandated.

Adrenergic Uptake Inhibitors↗

A case of serotonin syndrome and mutism associated with methadone.

A patient was seen on the palliative care service at our institution who developed serotonin syndrome and mutism associated with methadone use. Serotonin syndrome is often described as a clinical triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities, but not all of these findings are consistently present in all patients with the disorder. The incidence of the serotonin syndrome is thought to mirror the increasing number of proserotonergic agents being used in clinical practice. In 2002, the Toxic Exposure Surveillance System, which receives case descriptions from office-based practices, inpatient settings, and emergency departments, reported 26,733 incidences of exposure to selective serotonin-reuptake inhibitors (SSRIs) that caused significant toxic effects in 7349 persons and resulted in 93 deaths. Serotonin syndrome is not an idiopathic drug reaction; it is a predictable consequence of excess serotonergic agonism of central nervous system (CNS) receptors and peripheral serotonergic receptors. The myriad of symptoms with which serotonin syndrome may present is compounded by the fact that more than 85% of physicians are unaware of serotonin syndrome as a clinical diagnosis. Other SSRIs such as fluoxetine and fluvoxamine have been shown to increase methadone plasma concentrations in dependent patients. Although the exact mechanism is unknown, there are several pathways via which a significant interaction could occur. This would include the effects methadone has on N-methyl-D-aspartate (NMDA) in addition to the impact of methadone on the cytochrome P450 enzyme system. The mainstay of treatment of serotonin syndrome is withdrawal of the offending agent and supportive care. These actions resulted in resolution of our patient's symptoms. Serotonin syndrome is becoming more common, and with the utilization of polypharmacy on many palliative care services should be considered as unifying differential diagnosis in the appropriate setting.

Aged↗

A prospective study of urinary retention and risk of death after proximal femoral fracture.

Older age, dementia syndrome and impaired mobility are well recognized risk factors for fatality after fracture of the proximal femur. Urinary retention is recognized as a common complication of elective total hip replacement. In this investigation, we estimated the incidence of urinary retention associated with hip fracture in older women and assessed its relationship to 2-year post-operative fatality. Over a 7-month period, 309 women aged 65 and over were admitted to one trauma unit with hip fracture. Readings of post-voiding residual volume were taken on admission (pre-operative), within 24 hours of operation (post-operative) and 5-7 days post-operatively (recovery). Of the 309 patients, 244 (79%) had readings of post-voiding residual volume taken on admission; 90/244 (37%) had retention pre-operatively, 122/216 (56%) post-operatively and 40/183 (22%) in the recovery phase. One year after operation 305 patients were traced and median follow-up was 2 years. Older age, cognitive impairment, polypharmacy, impaired mobility and urinary retention on admission and during recovery were associated with a higher fatality in the first post-operative year. Pre-operative urinary retention is common among older women with proximal femoral fracture and affects over half post-operatively. Retention is one of several factors associated with higher fatality.

Aged↗

Enzymes of drug metabolism during delirium.

BACKGROUND: Delirium is common in ill medical patients. Several drugs and polypharmacy are recognised risk factors, yet little is known about drug metabolism in people with delirium. OBJECTIVE: The aim of this study was to investigate the activities of plasma esterases (drug metabolising enzymes) in delirium. DESIGN: This was a prospective study of delirium present at time of hospital admission (community acquired) or developing later (hospital acquired) in patients admitted as a medical emergency and aged 75 years or over. METHODS: Following informed consent or assent cognitive screening was completed on all patients on admission and every 48 hours subsequently. Delirium was diagnosed by Confusion Assessment Method and DSM IV criteria. Blood samples were taken on admission and at onset of delirium if this was later. Four plasma esterase assays were performed spectrophotometrically: acetylcholinesterase, aspirin esterase, benzoylcholinesterase, butyrylcholinesterase. RESULTS: 283 patients (71% of eligible) were recruited, with mean age 82.4 years and 59% female. 27% had community acquired delirium, 10% developed hospital acquired delirium, 63% never developed delirium. On admission the mean activities of all four esterase assays were statistically significantly lower in delirious than non delirious patients. There were no significant differences on admission in any plasma esterase activity between patients with hospital and community acquired delirium. In-hospital mortality was associated with low plasma esterase activities on admission. CONCLUSION: Plasma esterase activities are suppressed during delirium. These data reinforce the need for extreme caution with drugs in this vulnerable population.

Acetylcholinesterase↗

Treatment of hyperlipidemia in HIV-infected patients.

The treatment of hyperlipidemia in patients infected with HIV is discussed. Hyperlipidemia is common in HIV-infected patients receiving antiretroviral therapy, especially protease inhibitors and stavudine. The recommendations of the National Cholesterol Education Program (NCEP) may not entirely apply to HIV-infected patients. The pathogenesis of hyperlipidemia in these patients may make them refractory to traditional pharmacotherapy, and NCEP's emphasis on diet and exercise may be unrealistic. Other factors that may complicate treatment of hyperlipidemia include metabolism of many antiretroviral drugs by the cytochrome P-450 isoenzyme system, polypharmacy, and drug-food interactions. A patient's cardiac risk should first be assessed. Nonpharmacologic measures, such as a low-fat diet, weight reduction, and exercise, should be considered. Drug therapy is indicated for patients with familial combined hyperlipidemia that is associated with atherogenesis and for patients with triglyceride concentrations exceeding 1000 mg/dL. Drug therapy for hyperlipidemia involves niacin and statins, in addition to fibric acid derivatives and probucol. Switching among antiretroviral agents when one is found to cause hyperlipidemia should be done cautiously because of the risk for viral rebound and disease progression. NCEP guidelines recommend monitoring low-density-lipoprotein cholesterol levels four to six weeks after the start of lipid-lowering therapy and then at three months; more frequent monitoring may be necessary in HIV-infected patients. The treatment of hyperlipidemia in HIV-infected patients is complicated by their need for antiretroviral drugs, which can themselves contribute to lipid disorders.

Anti-HIV Agents↗

Gram-negative bacterial infections: a look at the past, a view of the present, and a glance at the future.

An overview of infections caused by gram-negative bacteria over the past 40 years discloses remarkable changes in their specific etiology and management. These organisms were responsible for disease in the preantibiotic era but at a much lower frequency than at present, and fatality rates were generally high. Bacteria such as Pseudomonas and Serratia, now relatively commonly involved in infection, rarely, if ever, caused disease before antibiotics became available. Although often present in surgical wounds, these organisms clearly were colonizers rather than pathogens. It is clear that the use of potent antimicrobial agents has been responsible for a general decrease in the fatality rates associated with gram-negative bacterial infections. However, it is evident that their use has been involved in the development of potentially lethal complications not seen in the past. Factors presently recognized as playing important roles in the problems associated with the treatment of gram-negative bacterial infections are the increasing number of older and sometimes debilitated patients and the longer survival of individuals with tumors or leukemia who, because of immunosuppression due to disease or treatment, are highly susceptible to invasion by almost any organism. Factors that have increased the magnitude of the problem of treatment of gram-negative bacterial infections include an increasing frequency of bacterial resistance to one or more antibiotics and a tendency of physicians to use more than one drug, sometimes as many as three or four, to treat gram-negative bacterial infections, especially in immunosuppressed people. Such polypharmacy is responsible for the development of suprainfections, some of which are caused by organisms very difficult to eradicate.

Anti-Bacterial Agents↗

Neurohormonal modulation in heart failure: ACE inhibition and beyond.

Angiotensin converting enzyme (ACE) inhibition undoubtedly has become the cornerstone of heart failure treatment. Useful in each stage, it should possibly be considered first-line treatment in many patients with mild heart failure in whom fluid retention is not clearly present. Careful consideration of the optimal dose for the individual is important. Until further data are available concerning the efficacy and tolerability of high and low doses, the clinician should consider the target doses used in large controlled heart failure trials. Even under optimal dosing conditions, it is likely that ACE inhibition may not suffice in completely modulating the extensive neurohormonal stimulation extant in heart failure. In part this may result from a breakthrough of the ACE inhibitor effect as well as from activation of hormones and peptides that may not be affected by ACE inhibition. Also, a substantial proportion of patients may not tolerate sufficient ACE inhibition. Alternative or additional therapy aimed at modulating neurohormonal activation concerns interference with other parts of the renin angiotensin system, such as angiotensin II receptor and aldosterone receptor antagonism. Sympathetic activity and catecholamine levels may decrease with dopaminergic D2 agonists and, possibly, beta-blockade; in the latter, this may be confined to patients with pre-existing sympathetic over-activation. Increasing circulating levels of atrial natriuretic peptide via neutral endopeptidase inhibition may offer an alternative way to increase diuresis and natriuresis without neuroendocrine stimulation. Novel possibilities that have not yet been tested sufficiently in patients with heart failure include endothelin receptor antagonism, arginine vasopressin antagonism, and renin inhibition. Finally, digitalis glycosides may be considered neurohormonal modulators in addition to being positive inotropes. Heart failure is a complex condition that involves many organs and systems besides the heart. Polypharmacy tailored to the individual is mandatory. It is thus necessary to investigate approaches to the modulation of neurohormonal activation beyond ACE inhibition.

Angiotensin Receptor Antagonists↗