Carlos Rojas-Fernandez

Treatment of Vitamin B12–Deficiency Anemia: Oral versus Parenteral Therapy

OBJECTIVE: To evaluate the use of oral cyanocobalamin therapy in the treatment of cobalamin (vitamin B12)–deficient anemia. DATA SOURCES: Primary and review articles were identified by MEDLINE search (1966–May 2000) and through secondary sources. DATA SYNTHESIS: Cobalamin-deficient anemia is among the most common diagnoses in older populations. Cobalamin-deficient anemia may be diagnosed as pernicious anemia, resulting from the lack of intrinsic factor required for cobalamin absorption or as protein malabsorption from the inability to displace cobalamin from protein food sources. Several studies provide evidence that daily oral cyanocobalamin as opposed to monthly parenteral formulations may adequately treat both types of cobalamin-deficient anemias. CONCLUSIONS: Daily oral cyanocobalamin at doses of 1000–2000 μg can be used for treatment in most cobalamin-deficient patients who can tolerate oral supplementation. There are inadequate data at the present time to support the use of oral cyanocobalamin replacement in patients with severe neurologic involvement.

Successful Use of Donepezil for the Treatment of Dementia with Lewy Bodies

OBJECTIVE: To report a case of the successful use of donepezil for treatment of cognitive and noncognitive symptoms in a patient with dementia with Lewy bodies. CASE SUMMARY: An 86-year-old white woman with dementia was experiencing early-onset significant fluctuation of her cognitive status, functional impairment, visual hallucinations, aggression, and parkinsonism. She was initially diagnosed with Alzheimer disease and Parkinsons disease and prescribed donepezil 5 mg/d and benztropine 1 mg twice daily. On reexamination of the case by a neurologist, the diagnoses were revised to dementia with Lewy bodies. The benztropine was discontinued, and donepezil was increased to 10 mg/d. The patients cognitive and functional status significantly improved, as did her visual hallucinations. DISCUSSION: This case supports previous reports of the marked responsiveness of patients with dementia with Lewy bodies to acetylcholinesterase inhibitors. This may be explained by the marked cholinergic deficit observed in patients with dementia with Lewy bodies and the evidence linking cognitive as well as noncognitive symptoms to this deficit. CONCLUSIONS: The present case suggests that patients with dementia with Lewy bodies respond well to acetylcholinesterase inhibitors. Controlled trials are necessary to further define the role of these drugs for this disease.

An assessment by the Statin Cognitive Safety Task Force: 2014 update.

The National Lipid Associations Safety Task Force convened a consensus conference of experts to develop a position statement on cognitive function to revise and update that published originally by the Association in the 2006 assessment of statin safety by a panel of neurologists. The current expert panel was charged with addressing the specific issue of potential adverse cognitive effects attributable to statins. Search strategies recently used in systematic reviews were used to identify relevant evidence using keywords and topics via Medline searches from 1966 to December 2013. Manual searches of bibliographies were also conducted. Panel members were asked to use the evidence to formulate answers to a series of questions of relevance to the subject matter. The strength of recommendations and quality of evidence were graded using accepted contemporary definitions and procedures. Recommendations to patients, health professionals, and researchers were put forth by the panel to aid in daily clinical decision making, and in future research endeavors.

Psychotropic Drugs and Falls: New Evidence Pertaining to Serotonin Reuptake Inhibitors

Falls are a significant cause of fatal and nonfatal injuries in older persons. Risk factors include previous falls, several disease states, and certain drugs such as tricyclic antidepressants and antihypertensives. We conducted a MEDLINE search from January 1966–March 1999 to identify studies and review articles on the association of neuroleptics, benzodiazepines, and antidepressants with fall risk in older people. The focus was on the risk associated with serotonin reuptake inhibitors, biologic plausibility, and limitations of these studies. It was thought that the agents did not increase the risk of falls, although recent evidence suggests that this is not the case.

Potential Interaction between Celecoxib and Warfarin

TO THE EDITO R : Celecoxib is a recently marketed nonsteroidal antiinflammatory drug with no significant effects on platelet aggregation or serum thromboxane production.1,2 Although the product monograph3 states that there is no drug interaction between warfarin and celecoxib, we recently observed a case in which administration of celecoxib to a patient receiving warfarin resulted in a significant increase in the patient’s i n t e rnational normalized ratio (INR). Case Report . An 88y e a r-old white woman with atrial fibrillation, osteoarthritis, glaucoma, hypertension, gout, and hypothyroidism was diagnosed with deep venous thrombosis on June 7, 1999, and prescribed warfarin 5 mg/d. Other medications included furosemide 40 mg/d, levothyroxine 125 μg/d, potassium chloride 10 mEq/d, diclofenac 50 mg and misoprostol 200 μg bid, felodipine 10 mg bid, allopurinol 300 mg/d, digoxin 125 μg/d, metaxalone 400 mg bid, Caltrate-D bid, a multivitamin, and calcitonin nasal spray. The patient was stabilized on warfarin 40 mg/wk (INR 2.7–3.1). Celecoxib 200 mg/d was started on July 8, and diclofenac/misoprostol was stopped (Figure 1). INR prior to starting celecoxib was 3.1. On July 13, the INR was 4.4 and on July 15, the INR further increased to 5.8. The patient experienced no complications, described no changes in dietary habits, and no changes in medication; all other laboratory indices were normal. Wa r f a r i n was withheld for two days and the dosage was reduced to 37.5 mg/wk. The INR decreased to 3.1 on July 20, and increased to 4.1 one week later. At that time, the warfarin dosage was reduced to 32.5 mg/wk. One week later, INR was 3.9, and the dosage was further reduced to 30 mg/wk. INR decreased to 3.0 within one week of this dosage adjustment. The total weekly warfarin dosage was 25% lower than before celecoxib was initiated. D i s c u s s i o n . Celecoxib undergoes hepatic metabolism by CYP2C9, which also is the isoform through which the S-enantiomer of warfarin is m e t a b o l i z e d .3 Although celecoxib did not appear to alter the pharm acokinetics of Ror S-warfarin in volunteers, it may cause an interaction in elderly patients.3 Various factors must be considered when designing pharmacotherapeutic regimens for geriatric patients, since they often consume multiple drugs, suffer from multiple diseases, and exhibit agerelated changes in pharmacokinetics such as decrements in renal and hepatic function.4 Indeed, an age-related decrease in the content and function of CYP2C9/10 has been documented.5 Also germane is a study by Mungall et al.,6 in which warfarin clearance decreased 1% each year in patients 18–70 years old. As we could find no other obvious reason for INR elevation, these events emphasize the importance of close monitoring of patients receiving these drugs concomitantly. This is especially true in geriatric patients who are at high risk for drug interactions and who require more stringent INR monitoring. On the Naranjo7 probability scale the score indicated a probable likelihood that celecoxib caused the increase in INR. Although additional studies are needed to further delineate the mechanism and clinical significance of the proposed celecoxib–warfarin interaction, we advocate monitoring INR on two occasions three to seven days after the initiation of celecoxib to assess its effect on the patient’s INR. It should also be noted that similar cases8 , 9 have been reported to the manufacturer and the Food and Drug Administration, and that rofecoxib also has been noted to increased INR.8 , 9

Undertreatment of osteoporosis in residents of nursing homes: population-based study with use of the Systematic Assessment of Geriatric Drug Use via Epidemiology (SAGE) database.

OBJECTIVE To determine the proportion of nursing home residents >65 years of age with osteoporosis who were receiving antiosteoporosis pharmacotherapy and to identify the predictors of administration of such drugs. METHODS We identified 29,357 patients with osteoporosis documented on the Minimum Data Set collected on residents of all nursing home facilities in 5 states during the period from 1992 through 1996. A multiple logistic regression model was used for analysis, with the dependent variable being use of any antiosteoporosis drug. RESULTS Among the nursing home residents with osteoporosis, 25% received antiosteoporosis drugs. Women were more likely than men to receive antiosteoporosis drugs (adjusted odds ratio [OR], 1.41; 95% confidence interval [CI], 1.26 to 1.57). Both increasing age and level of cognitive impairment were inversely related to receipt of antiosteoporosis drugs. A history of fracture or falls was not predictive of use of such drugs. Treatment was less likely for nursing home residents with > or = 6 medical conditions (OR 0.55, 95% CI 0.51 to 0.59); those admitted to a nursing home from a hospital (OR 0.86, 95% Cl 0.80 to 0.92); and those with a terminal prognosis (OR 0.60,95% CI 0.42 to 0.87). CONCLUSION The majority of nursing home residents with osteoporosis in this study did not receive drug therapy for this disabling and treatable disease. Although acceptable reasons may exist in some of these residents,others--especially the oldest old--may not be receiving adequate care.

Pharmacotherapy of behavioral and psychological symptoms of dementia: time for a different paradigm?

Behavioral and psychological symptoms of dementia can occur in 60–80% of patients with Alzheimers disease or other dementing illnesses, and are important in that they are a source of significant caregiver stress and often precipitate nursing home placement. These symptoms, namely, aggression, delusions, hallucinations, apathy, anxiety, and depression, are clinically managed with a variety of psychotropic drugs such as antipsychotics, antidepressants, antiepileptic drugs, and benzodiazepines. Various advances in the neuropathophysiology and pharmacotherapy must be considered in the optimal design of regimens for patients with these symptoms.

Methodology for Developing Deprescribing Guidelines: Using Evidence and GRADE to Guide Recommendations for Deprescribing.

Background Class specific deprescribing guidelines could help clinicians taper and stop medications no longer needed or which may be causing more harm than benefit. We set out to develop methodology to create such guidelines using evidence-based methods for guideline development, evidence synthesis and recommendation rating. Methods and Findings Using a comprehensive checklist for a successful guideline enterprise, we conducted a national modified Delphi consensus process to identify priorities for deprescribing guidelines, then conducted scoping exercises to identify feasible topics, and sequentially developed three deprescribing guidelines. We selected guideline development team members for clinical expertise; a GRADE member worked with staff to ensure guideline development processes were followed. We conducted or used systematic searches and reviews of deprescribing trials of selected drug classes, reviews or systematic reviews of drug class effectiveness, reviews of reviews of drug class harm and narrative syntheses of contextual questions to inform recommendations and guideline development. Our 8 step process for guideline development included defining scope and purpose, developing a logic model to guide the process and generate key clinical questions, setting criteria for admissible evidence and conducting systematic reviews, synthesizing evidence considering additional contextual information and performing quality estimates, formulating recommendations and providing strength estimations, adding clinical considerations, conducting clinical and stakeholder review and finally updating content pre-publication. Innovative aspects of the guideline development process included synthesizing evidence for outcomes of tapering or stopping medication, and incorporating evidence for medication harm into the recommendation strength rating. Through the development of three deprescribing guidelines (for proton pump inhibitors, benzodiazepine receptor agonists and antipsychotics) and associated decision-support algorithms, we were able to gradually hone the methodology; each guideline will be published separately. Conclusion Our methodology demonstrates the importance of searching for short and long-term outcomes, showing the benefits of deprescribing and studying patient preferences. This publication will support development of future deprescribing guidelines.

Considerations in the treatment of geriatric depression: Overview of pharmacotherapeutic and psychotherapeutic treatment interventions.

Geriatric (or late-life) depression is common in older adults, with an incidence that increases dramatically after age 70 to 85, as well as among those admitted to hospitals and those who reside in nursing homes. In this population, depression promotes disability and is associated with worsened outcomes of comorbid chronic medical diseases. Geriatric depression is often undetected or undertreated in primary care settings for various reasons, including the (incorrect) belief that depression is a normal part of aging. Current research suggests that while antidepressant agent use in older adults is improving in quality, room for improvement exists. Improving the pharmacotherapy of depression in older adults requires knowledge and understanding of many clinical factors. The purpose of this review is to discuss salient issues in geriatric depression, with a focus on pharmacotherapeutic and psychotherapeutic interventions.

Atypical antipsychotics for insomnia: a systematic review

BACKGROUND Observational evidence suggests that atypical antipsychotics such as quetiapine are increasingly being used to manage insomnia. This is concerning given the uncertain efficacy and potential adverse effects associated with these medications. OBJECTIVES The objectives of this study are to evaluate the benefits and adverse effects of atypical antipsychotics used specifically for insomnia. METHODS The methods used in this study are systematic review and narrative synthesis. DATA SOURCES The data were collected from PubMed; EMBASE; Cochrane Library; PsycINFO; grey literature; and the manufacturers of risperidone, quetiapine and olanzapine. PARTICIPANTS AND INTERVENTIONS Adult patients ≥18 years of age using atypical antipsychotics specifically for primary or co-morbid insomnia for ≥ 1 week were compared to those receiving active intervention or placebo. APPRAISAL AND SYNTHESIS METHODS Two independent reviewers screened titles, abstracts and full-text articles; extracted data; and conducted risk-of-bias analysis. Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment was completed. RESULTS One double-blind randomized controlled trial (n = 13) met the eligibility criteria. Statistically significant differences were not observed from baseline between quetiapine and placebo after 2 weeks for primary insomnia in terms of total sleep time (mean difference (MD) 52.68 min, 95% CI -27.27 to 132.6), reduction in sleep latency (MD 72.44 min, 95% CI -2.65 to 147.5) or improved sleep satisfaction measured with a visual analogue scale out of 100 (MD 6.16, 95% CI -12.32 to 24.64), despite a trend towards improved sleep parameters. The study was rated as very low quality. CONCLUSIONS AND IMPLICATIONS Very low quality evidence suggests that quetiapine does not significantly improve sleep parameters compared with placebo in primary insomnia, despite a trend towards clinical improvements. Atypical antipsychotics should be avoided in the first-line treatment of primary insomnia until further evidence is available.