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PubMed2000

Diagnosis and treatment of gastroesophageal reflux disease in the elderly.

Gastroesophageal reflux disease poses special diagnostic and therapeutic challenges in the elderly. These patients may not report the classic symptoms of dysphagia, chest pain, and heartburn, and they are more likely to develop severe disease and complications such as esophageal ulceration and bleeding. Therapeutic options include lifestyle changes, medication, and surgery. Polypharmacy and changes in renal, hepatic, and gastrointestinal function can complicate treatment. Proton pump inhibitors can help optimize disease management. The most common primary presenting symptoms of GERD in the elderly are regurgitation, dysphagia, dyspepsia, vomiting, and noncardiac chest pain, rather than heartburn. Because the elderly commonly take multiple drugs for various comorbidities, drug interactions and treatment responses must be carefully assessed in this patient population. Nonpharmacologic measures may be helpful but often do not relieve nighttime GERD symptoms.

Age Factors↗
PubMed2004

Should nursing home residents with atrial fibrillation be anticoagulated?

Most long-term care residents with atrial fibrillation would be at high risk for embolic stroke based on age and comorbidities according to the criteria presented here. Additionally, they are theoretically excellent candidates for adjusted-dose warfarin treatment for atrial fibrillation. They are accessible for monitoring and tend to have less dietary variability, a controlled medication list, and supervised medication administration. Balancing these features is at least a moderate risk of severe bleeding from anticoagulation based on age, comorbidities, and polypharmacy. However, studies suggest that even those long-term care residents identified as ideal candidates for anticoagulation may not receive warfarin. Those residents who do receive warfarin may not be anticoagulated within the therapeutic range much of the time. This treatment pattern may expose older adults with a high stroke risk to dying from a cardioembolic stroke or to acquiring functional deficits that make them more dependent and lower their quality of life.

Adult↗
PubMed1992

The elderly neuroscience patient: implications for the critical care nurse.

The elderly patient may present to the critical care unit with neurologic deficits such as acute confusion, loss of consciousness, or signs of a cerebrovascular accident. Recognizing the normal age-related changes that occur in the nervous system enables the critical care nurse to evaluate the patient's response to neurologic disorders. The normal neurologic changes associated with aging provide implications for assessment, response to the critical care environment, and the time needed for education and rehabilitation. Other changes, especially decreased immunity, malnutrition, and pulmonary and cardiac pathology, significantly increase the risk for morbidity and mortality after an acute neurologic event. Changes in pharmacokinetics and the likelihood of polypharmacy in the older patient greatly increase the risk for complications and side effects of the commonly used treatments. Important elements of nursing management for the elderly neuroscience patient include performing an accurate neurologic assessment, including noting changes in cognition, observing for adverse drug reactions, optimizing ventilation, and maximizing mobility and nutritional status. This article focuses on these aspects of nursing care for the elderly neuroscience patient.

Aged↗
PubMed2000

Surviving heart failure: Robert L. Frye lecture.

Heart failure is increasing in both incidence and prevalence and is associated with a high mortality. In patients with heart failure, coronary artery disease is the cause for about two thirds. Pathophysiologic changes have been linked to altered muscle function and hemodynamics, elevated neurohormones, and, more recently, cellular mechanisms, including apoptosis. Standard triple therapy for symptomatic heart failure consists of an angiotensin-converting enzyme (ACE) inhibitor, digoxin, and a diuretic. In patients with severe heart failure, spironolactone should be added. In large clinical trials, ACE inhibitors, spironolactone, and beta-blockers have reduced mortality. Other drugs may be helpful in the treatment of heart failure. Amiodarone is the antiarrhythmic drug of choice in patients with symptomatic arrhythmias and also has a role in the treatment of dilated cardiomyopathy. Angiotensin II receptor blockers are being compared with ACE inhibitors and appear promising. Newer agents being tested include antagonists to endothelin and tumor necrosis factor. Overall, it is clear that polypharmacy is the standard of care for patients with heart failure. A future challenge will be to prevent heart failure from occurring.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Pharmacogenomics: a clinician's primer on emerging technologies for improved patient care.

Pharmacogenomics is a term recently coined to embody the concept of individualized and rational drug selection based on the genotype of a particular patient. Customization of drug therapy offers the potential for optimal safety and efficacy in an individual patient. Such a process contrasts current prescribing practices, which use medications shown to be safe and effective in patient populations or based on anecdotal experiences. Within patient populations, medications vary in their efficacy among individual patients. More importantly, a medication that is safe and effective in one patient may be ineffective or even harmful in another. Underlying many of these phenotypic differences are genotypic variants (polymorphisms) of key enzymes and proteins that affect the safety and efficacy of a drug in an individual patient. An understanding of these polymorphisms has the potential to enhance patient care by allowing physicians to customize the selection of medication to meet individual patient needs. Pharmacogenomics may also lead to improved compliance and shorter time to optimal disease management, thereby reducing morbidity and mortality. Significant cost savings could result from reductions in polypharmacy as well as from fewer physician encounters and hospitalizations for exacerbations of underlying illness and because of adverse drug reactions.

Case Management↗
PubMed2004

Inappropriate medications for elderly patients.

The use of medications is common in elderly persons, and this population has the highest risk of medication-related problems. Elderly persons are more susceptible to the effects of various medications for a number of reasons. It is well known that polypharmacy is one of the most serious problems in caring for elderly persons; however, many of these patients continue to receive medications that have an increased risk of causing harm. In 1991, an important article was published about inappropriate medication use in the elderly population. This article raised awareness of the problem and presented explicit criteria for determining which medications were inappropriate for elderly patients residing in long-term care facilities. This list of drugs is still used for evaluating medications taken by elderly persons and for determining whether satisfactory prescribing practices are being used. We reviewed the medications described as inappropriate for elderly persons and searched the scientific literature to determine whether evidence exists to defend or refute the labeling of particular drugs. At times, evidence was difficult to find, and many of the original studies were dated. For most medications listed as inappropriate, we found evidence to support these designations.

Aged↗
PubMed2000

The increasing use of polypharmacotherapy for refractory mood disorders: 22 years of study.

BACKGROUND: Few studies have approached the subject of polypharmacotherapy systematically. This retrospective review of 178 patients with refractory bipolar disorder or unipolar depression (Research Diagnostic Criteria or DSM-III-R criteria) discharged from the National Institute of Mental Health (NIMH) Biological Psychiatry Branch between 1974 and 1996 was conducted to assess the degree and efficacy of "add-on" pharmacotherapy. METHOD: Following completion of formal structured blinded research protocols, patients entered a treatment phase (often again on a blind basis) in which all agents available in the community could be utilized. Each patient's retrospective life chart and all prospective double-blind nurse- and self-rated NIMH data were reviewed. The overall degree of improvement at discharge was assessed by rating on the Clinical Global Impressions scale (CGI) as modified for bipolar illness (CGI-BP). RESULTS: A 78% improvement rate (moderate or marked on the CGI) was achieved at the time of discharge. There was a significant relationship between number of medications utilized at discharge as a function of discharge date (r = 0.45, p < .0001). The percentages of patients discharged on treatment with 3 or more medications were 3.3% (1974-1979), 9.3% (1980-1984), 34.9% (1985-1989), and 43.8% (1990-1995). No correlation was found between polypharmacy and age (r = -0.03, p = .66). Patients more recently discharged from the NIMH had an earlier age at illness onset, more lifetime weeks depressed, and a higher rate of rapid cycling than patients in the earlier cohorts. CONCLUSION: Increasing numbers of medications in more recent NIMH cohorts were required to achieve the same degree of improvement at hospital discharge. More systematic approaches to the complex regimens required for treatment of patients with refractory mood disorder are clearly needed.

Adult↗
PubMed2000

Mood stabilizers during breastfeeding: a review.

BACKGROUND: The postpartum period is an exceptionally high-risk time for recurrence of depression, mania, or psychosis for women with bipolar disorder. Puerperal prophylaxis with mood stabilizers decreases this risk. To allow patients and clinicians to make informed decisions about mood-stabilizer use during breastfeeding, there is a need for a critical review and analysis of the data. DATA SOURCES: A search of MEDLINE (1966-1998) and the Lithium Database, Madison Institute of Medicine, was conducted to obtain articles about lithium, valproate, carbamazepine, gabapentin, or lamotrigine use during lactation. Search terms used were pregnancy, teratogenesis, breastfeeding, lactation, breast milk levels and lithium, anticonvulsants, mood stabilizers. No other search restrictions were used. Unpublished data on gabapentin and lamotrigine were provided by the manufacturers. RESULTS: The search revealed 11 cases of lithium use during breastfeeding, 8 of which reported infant serum levels. Two cases reported symptoms consistent with lithium toxicity in the infants. Thirty-nine cases of valproate use during breastfeeding were found, 8 of which reported infant serum levels. There was 1 report of thrombocytopenia and anemia in an infant. Fifty cases of carbamazepine use during breastfeeding were found, 10 of which reported infant serum levels. Two infants experienced hepatic dysfunction. One unpublished study of gabapentin in breast milk was found. Three reports of lamotrigine use during breastfeeding were found. DISCUSSION: Available information remains limited to uncontrolled studies and case reports. Carbamazepine and valproate, but not lithium, have generally been considered compatible with breastfeeding. The overall paucity of data, data confounded by polypharmacy and infant age differences, and adverse reactions reported with all established mood stabilizers dictate a reassessment of these recommendations. We propose that a woman's historical response to medication and the clinical circumstances be the primary considerations when choosing a mood stabilizer during breastfeeding, rather than strict adherence to categorical assignments.

Acetates↗
PubMed2003

Prior antipsychotic prescribing in patients currently receiving clozapine: a case note review.

BACKGROUND: Clozapine is indicated for the treatment of resistant schizophrenia, which is usually defined as failure to respond to adequate trials of 2 antipsychotics. It is thought that only clozapine is likely to be effective in such cases and that other drugs are ineffective. We sought to discover prior patterns of antipsychotic prescribing in schizophrenic patients eventually prescribed clozapine. METHOD: Prescribing histories were obtained from prescription charts and case notes for all inpatients prescribed clozapine in 4 hospitals in southeast London during April 2001. RESULTS: 120 patients were identified, of whom 112 had been diagnosed with schizophrenia or schizoaffective disorder and whose data were analyzed. The mean duration of illness was 15.1 years. Subjects had experienced a mean of 9.2 (range, 2-35) episodes of antipsychotic prescription before clozapine was first used, with 5.7 (range, 0-25) episodes constituting adequate trials (drug used at therapeutic dose for 6 weeks). The mean number of different antipsychotics used was 5.5 (range, 1-13), with a mean of 4.0 (range, 0-12) given an adequate trial. Ninety percent of patients (N = 101) had received an atypical antipsychotic before first use of clozapine, and 65% (N = 73) had previously received antipsychotic polypharmacy. The mean maximum theoretical delay in using clozapine was 5.0 years (range, 0-11.1 years). Longer delay was significantly (p <.05) associated with being aged over 30 years at the time of the study, being diagnosed with psychotic illness before the introduction of clozapine, and completing adequate trials of 2 different antipsychotics before the introduction of clozapine or risperidone. CONCLUSION: Clozapine treatment was quite likely delayed for longer than is clinically desirable. This delay may have important effects on quality of life, clinical outcome, and health resource utilization.

Antipsychotic Agents↗
PubMed2004

Mental health service utilization by borderline personality disorder patients and Axis II comparison subjects followed prospectively for 6 years.

OBJECTIVE: The purpose of this study was to describe the psychiatric treatment received by a well-defined sample of patients with borderline personality disorder and Axis II comparison subjects over 6 years of prospective follow-up. METHOD: 362 inpatients were interviewed about their treatment histories during their index admission (1992-1995). 290 patients met both Revised Diagnostic Interview for Borderlines and DSM-III-R criteria for borderline personality disorder and 72 met DSM-III-R criteria for at least 1 nonborderline Axis II disorder (and neither criteria set for borderline personality disorder). Over 94% of surviving patients were re-interviewed about their psychiatric treatment histories 2, 4, and 6 years later. RESULTS: Only 33% of borderline patients were hospitalized during the final 2 years of the 6-year follow-up, a substantial decline from the 79% who had prior hospitalizations at baseline. Much the same pattern emerged for day and/or residential treatment (from 55% to 22%). In contrast, about three quarters of borderline patients were still in psychotherapy and taking psychotropic medications after 6 years of follow-up. Additionally, over 70% of borderline patients participating in these outpatient modalities did so for at least 75% of each follow-up period. While rates of intensive psychotherapy declined significantly over time (from 36% to 16%), rates of intensive polypharmacy remained relatively stable over time, with about 40% of borderline patients taking 3 or more concurrent standing medications during each follow-up period, about 20% taking 4 or more, and about 10% taking 5 or more. CONCLUSIONS: The results of this study suggest that the majority of borderline patients continue to use outpatient treatment in a sustained manner through 6 years of follow-up, but only a declining minority use more restrictive and costly forms of treatment.

Adolescent↗
PubMed2005

Carnitine levels in valproic acid-treated psychiatric patients: a cross-sectional study.

BACKGROUND: Carnitine facilitates the transport of long-chain fatty acids across the mitochondria for beta oxidation, and the removal of potentially toxic acylcoenzyme-A metabolites from the inner aspect of mitochondrion as acylcarnitines. Previous studies suggest a significant decrease in carnitine concentrations and changes in the ratio of acylcarnitine to free carnitine in seizure-disoriented patients treated with valproic acid (VPA), which may lead to clinical manifestations of carnitine deficiency. This study sought to explore whether the same decrease in plasma free carnitine and increase in acylcarnitines are seen when VPA is used in the treatment of patients with psychiatric disease. METHOD: Thirty psychiatric patients treated with VPA for at least six months were selected for the study and granted informed consent for participation. Exclusion criteria included liver disorder or pancreatitis, metabolic defects known to affect plasma carnitine levels, or noncompliance with VPA regimen. Plasma free carnitine, total carnitine, VPA, and amylase levels were determined, and liver function tests (LFTs) were performed. Pearson correlations were conducted between VPA levels, levels and ratios of carnitines, as well as LFTs and amylase levels. RESULTS: Plasma free and total carnitine levels were lower than the reported normal range for the laboratory performing the assay, and the ratio of acylcarnitine to free carnitine was increased. There was a significant positive correlation of VPA levels and acylcarnitine-free carnitine ratio, a trend toward significance between VPA levels and acylcarnitine levels, and a marginal negative correlation between VPA levels and free carnitine levels. VPA levels correlated also with several LFTs and acylcarnitine levels. Octanoyl carnitine and acylcarnitine levels, as well as acylcarnitine-free carnitine and octanoyl-free carnitine ratios, correlated significantly with amylase levels. CONCLUSION: Although the study was limited by a cross-sectional design without direct control comparison, the findings suggest that patients with various psychiatric conditions treated with polypharmacy that includes VPA may have lower plasma carnitine levels than would be expected in healthy controls.

Adult↗
PubMed2001

Recognition and Management of Behavioral Disturbances in Dementia.

Behavioral disturbances are seen in most patients with dementia at some point in their course. They cause immense patient suffering and are responsible for caregiver stress, institutionalization, and hospitalization. Identification of predisposing and precipitating factors is very important. The approach to the management of behavioral disturbances in dementia patients should be structured and thorough. Ensuring the safety of the patient and others should be paramount. Addressing the causes of behavioral disturbances such as comorbid medical illnesses, polypharmacy, pain, personal need, environmental factors, etc. is critical to a successful outcome. Many behavioral disturbances such as wandering and hoarding are not amenable to pharmacotherapy. Nonpharmacologic interventions are the mainstay of managing behavioral disturbances. Success of pharmacologic interventions will depend on accurate identification of specific syndromes, e.g., depression-anxiety and psychosis and severity of symptoms. Response to pharmacologic interventions is usually modest and may be associated with significant symptom resolution. Many behavioral disturbances can be prevented by avoiding inappropriate medications and educating patient, family, caregivers, and health care providers. Hospitalization can be avoided and institutionalization delayed by early recognition and treatment of behavioral disturbances. Leadership from physicians to implement preventive measures is recommended. Research to clarify the biological underpinnings of behavioral disturbances and to address cost-effectiveness of currently identified interventions is needed.

Journal Article↗
PubMedDate not supplied

Glycemic control and prevention of microvascular and macrovascular disease in the Steno 2 study.

OBJECTIVE: To review key findings and insights from the Steno 2 trial involving 160 patients with type 2 diabetes in Denmark. METHODS: The Steno 2 study design, with conventional and intensive treatment arms, is described, and the outcomes are summarized. RESULTS: Intensive and target-driven behavior modeling and polypharmacy for 7.8 years induced an absolute risk reduction of 20% in cardiovascular disease events in patients with type 2 diabetes and the metabolic syndrome in comparison with a conventional multifactorial treatment. The relative risk reduction found for microvascular events after 4 years was maintained at a similar level after 7.8 years of intervention: nephropathy 61%, retinopathy 58%, and autonomic neuropathy 63%. CONCLUSION: Improving glycemic control in patients with type 2 diabetes may be as important as, or even more important than, treating hypertension and dyslipidemia for the prevention of both microvascular and macrovascular complications, particularly when aggressive treatment is initiated at an early stage of the disease.

Blood Glucose↗
PubMed2005

Antipsychotic use in patients with schizophrenia treated in private psychiatry.

QUESTIONS UNDER STUDY: The aim of this study was to assess antipsychotic treatment practices among private psychiatrists in Switzerland. METHODS: For each patient seen during 4 consecutive weeks, 101 participating private psychiatrists documented psychiatric diagnosis. For each schizophrenic patient, demographic details as well as treatment issues were assessed in a questionnaire-based survey. Participating psychiatrists were representative for Swiss private psychiatry with regards to gender distribution and region of practice. RESULTS: Overall, 8425 patients were assessed in our survey. Of these, 905 patients (10.7%) received a diagnosis of schizophrenic psychoses, of whom 733 details on antipsychotic treatment were documented. 73.1% of these patients received second generation antipsychotics. Most private psychiatrists prescribed antipsychotic monotherapy and maintained antipsychotic treatment according to recommendation from international guidelines. Almost half of these patients had a history of medication non-adherence, with non-compliance being the most frequent reason. CONCLUSION: The findings of this survey suggest that Swiss private psychiatrists prescribe according to international guidelines in terms of drug choice as well as maintenance treatment. Moreover they show low rates of polypharmacy and comedication practice as compared to their colleagues in other European countries. This may reflect solid experience in prescribing second-generation antipsychotics of a subgroup of private psychiatrists in Switzerland.

Adult↗
PubMed2004

Therapeutic drug monitoring of trazodone: are there pharmacokinetic interactions involving citalopram and fluoxetine?

OBJECTIVE: Therapeutic drug monitoring (TDM) of the new generation antidepressants is subject of controversial discussion. Nonetheless, TDM may safeguard against drug-drug interactions, can be used to control compliance and is valuable in the investigation of overdose. METHOD: The aim of this prospective study was to investigate serum levels of trazodone when prescribed as monotherapy or when used in combination with the selective serotonin reuptake inhibitors citalopram and fluoxetine in a simultaneous assay using high-performance liquid chromatography (HPLC). Over a 1-year period, we studied 97 patients (63 females) with depressive syndrome who were subdivided into 3 main diagnostic groups. Fifty-two patients were smokers, the mean age was 39.9 years and the mean weight was 72.4 kg; 40 patients were taking trazodone alone, 41 trazodone in combination with citalopram and 16 patients trazodone in combination with fluoxetine. RESULTS: The use of citalopram and fluoxetine in combination with trazodone had no significant impact on trazodone serum levels, and the same was true for differences in body weight and smoking behavior. On the other hand, age and sex had a significant influence on the pharmacokinetic pattern of trazodone, causing higher concentrations in females and in older patients. Since the polypharmacy investigated did not change the serum levels of trazodone, we assume that there is no metabolic interaction between trazodone and citalopram and trazodone and fluoxetine. We observed none of the adverse effects which might have been expected, including dizziness, severe headache, daytime sedation, fatigue or the serotonin syndrome even in a mild form. CONCLUSION: A "double-tracked" antidepressive treatment using trazodone and the SSRIs citalopram and fluoxetine is associated with a wide safety margin.

Adult↗
PubMed2005

Drug-induced gastrointestinal disorders in surgical patients admitted to the University Hospital, Jena, Germany.

The use of drugs is always accompanied by the risk of adverse drug reactions (ADRs). Particularly important among these are serious ADRs that require hospital admission. Such cases often include patients with gastrointestinal ADRs and many reports have been published on drug-induced gastrointestinal bleeding and ulcers. The objective of the project described here was to detect gastrointestinal ADRs by systematic screening of all medical files in three university departments of surgery, i.e. visceral surgery, vascular surgery and traumatic surgery in the University Hospital of Jena, Germany. The study was retrospective involving the analysis of patients records for the period January 1, 2000 to June 30, 2001. The evaluation concerned all the medical files of individual patients in surgery and in particular those with gastrointestinal disorders due to adverse drug reactions. Side effects were classified according to their severity, duration, symptomatology and pathogenesis and assessed according to frequency, age and sex of the patient and the surgical unit in which the side effect was being treated. Out of a total of 7,715 patients evaluated in the university surgical departments, 471 (6.1%) had gastrointestinal disorders, in 144 (1.9%) of these patients 202 adverse drug reactions were diagnosed and in 70 patients (49.3%) the adverse drug reactions affecting the gastrointestinal tract were classified as serious. Gastric ulcers were present in 86 patients (42.6%) and intestinal ulcerations in 62 patients (30.7%) with intestinal bleeding occurring in 21 (10.4%). In 33 patients (16.3%) the etiology of the gastrointestinal bleeding was uncertain. The average age of patients with gastrointestinal ADRs was 66.1 years in men and 74.4 years in women. Only 1.7% of our patients were aged below 40 years. In approximately 20% of patients analgetic drugs had been withdrawn because of side effects. It is known that there is a correlation between polypharmacy, multiple morbidity and advancing age. The relationship however is complex and the extent to which age is a causative factor in ADRs is difficult to determine. In addition, it is often difficult to obtain clear documentation on the drug history prior to admission to hospital. Physicians are usually unable to devote enough time for a thorough analysis of adverse drug effects and there is a need to correct this deficiency.

Adverse Drug Reaction Reporting Systems↗
PubMedDate not supplied

Successful limb salvage with prostaglandin infusion: a review of ergotamine toxicity.

OBJECTIVE: A case of severe acute peripheral arterial insufficiency secondary to ergotamine toxicity treated successfully with intravenously administered prostaglandin is presented to highlight the features of this condition and to demonstrate the efficacy of treatment with prostaglandin infusion. CLINICAL FEATURES: A 35-year-old unemployed Caucasian woman with a background of polypharmacy abuse and recurrent migraines presented to St Vincent's Hospital Emergency Department with limb-threatening ischaemia of both legs secondary to chronic ergotamine overuse. INTERVENTION AND OUTCOME: A prostaglandin infusion was started and a dramatic and rapid improvement of her peripheral circulation occurred within six hours. CONCLUSION: Ergotamine toxicity is an uncommon but well documented cause of peripheral vascular insufficiency that should be recognised and treated aggressively because its sequelae can be disastrous. Intravenously administered prostaglandin proved to be successful in this case and is a logical choice as first-line therapy for ergotamine toxicity.

Adult↗
PubMed1993

Drug-induced disorders of glucose tolerance.

PURPOSE: To review the medications that influence glucose metabolism and to examine the mechanisms of these medications on glucose metabolism. DATA SOURCES: Data were obtained from a MEDLINE search back to 1966 and included animal and human studies published in the English language. STUDY SELECTION: Approximately 80% of original publications were included after review by the authors. Case reports were included if they provided additional information. DATE EXTRACTION: The original data from the literature were included on the basis of independent extraction by the authors. DATA SYNTHESIS: Many common therapeutic agents influence glucose metabolism. Multiple mechanisms of action on glucose metabolism exist through pancreatic, hepatic, and peripheral effects. Based on circumstances at the time of use, a drug may cause both hyper- and hypoglycemia in a patient. The patient's previous pancreatic reserve, nutritional state, use of other medication, or exposure to alcohol may influence the direction of the plasma glucose alterations. CONCLUSION: Hyperinsulinemia and insulin resistance form an intrinsic component of diabetes, hyperlipidemia, and atherosclerotic vascular disease (syndrome X). The induction of hyperinsulinemia and insulin resistance by medication may therefore counteract intended benefits. An extensive review of recent medication in patients with disorders of glucose tolerance and the avoidance of polypharmacy are recommended. It is prudent to monitor plasma glucose values when it is not possible to avoid prescription of medication with known effects on carbohydrate metabolism.

Animals↗