bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying the Clinical Significance of Drug—Drug Interactions: Scaling Pharmacists' Perceptions of a Common Interaction Classification Scheme
Authors: Roberts James S , Watrous Marc L , Schulz Richard M , Mauch Robert P , Nightengale Brian S 
Published: January 2017

OBJECTIVE: To develop a precise, interval level scale of the clinical significance of drug—drug interactions that reflects the professional judgments of practicing pharmacists. PARTICIPANTS: A convenience sample of 63 practicing pharmacists representing hospital (clinical and staff) and retail (chain and independent) practice settings. METHOD: Pharmacists judged the similarity among 15 interaction categories that have been commonly used to classify drug—drug interactions. A multidimensional scaling technique produced a spatial representation (i.e., a psychological map) of the structure inherent in those similarity judgments. Pharmacists' ratings of clinical significance were projected onto that same spatial representation using a multiple regression procedure, and the resulting information was used to develop a scale of clinical significance. RESULTS: The clinical significance scale developed from pharmacists' judgments was substantially different from a comparison scale published in a popular reference. The new scale was more precise than the comparison scale, and it also approximated an interval level of measurement. The judgments used to produce the new clinical significance scale were not reliably influenced by pertinent demographic characteristics of the sample. CONCLUSIONS: Inconsistencies between published clinical significance scales and the professional judgments of practitioners could affect patient care to the degree that a summary measure of clinical significance affects a practitioner's response to a potential drug—drug interaction. The clinical significance scale developed in this study has good measurement characteristics and reflects the professional judgments of practicing pharmacists. Use of the new scale is recommended on these grounds, although further assessment of its generality is warranted.
Cholestyramine Ointment to Treat Buttocks Rash and Anal Excoriation in an Infant
Authors: White C Michael , Gailey Ronald A , Lippe Scott 
Published: January 2017

OBJECTIVE: To describe a novel treatment for perianal excoriation in an infant receiving a promotility agent. CASE SUMMARY: A 2-month-old boy with reflux and regurgitation was treated with cisapride. Shortly after cisapride therapy he developed a rash on his buttocks and anal irritation that progressed in severity despite the use of numerous topical products and extended diaper-free periods. A topical cholestyramine ointment compound was prepared and administered, resulting in complete resolution within 3 days. DISCUSSION: Cisapride can decrease the gastrointestinal transit time, which can lead to less time for bile acid reabsorption in the distal ileum. If high concentrations of bile acids are contained in the stool, they can irritate the anus and buttocks in a manner similar to the skin irritation experienced by patients with ostomies. Cholestyramine, a bile acid sequestrant, can irreversibly bind the bile when applied topically and bring relief to the patient. CONCLUSIONS: Topical cholestyramine ointment may be a safe and efficacious treatment option for perianal irritation due to bile acids.
Cetirizine versus Hydroxyzine and Placebo in Chronic Idiopathic Urticaria
Authors: Breneman Debra L. 
Published: January 2017

OBJECTIVE: To compare the safety and efficacy of cetirizine with that of hydroxyzine and placebo in the treatment of chronic idiopathic urticaria. DESIGN: A 4-week multicenter, randomized, double-blind, double-dummy, placebo-controlled safety and efficacy study. SETTING: Patients were treated in a variety of allergy practice settings. PATIENTS: The study population consisted of 188 patients who were at least 12 years of age, with symptomatic chronic idiopathic urticaria that had occurred episodically for at least 6 weeks. INTERVENTIONS: Patients were given either cetirizine 10 mg once daily, hydroxyzine 25 mg tid, or placebo for 4 weeks. MAIN OUTCOME MEASURES: Patients and investigators used a 4-point scale to evaluate symptoms of urticaria and adverse effects of treatment. Ratings were compared among those taking cetirizine, hydroxyzine, or placebo. RESULTS: After 1 day of treatment, patients randomized to receive cetirizine 10 mg/d exhibited a reduction in the number of episodes of urticaria (and a reduction in pruritus) compared with patients who received hydroxyzine 25 mg tid and patients who received placebo (p = 0.002). The number of urticarial episodes in patients treated with hydroxyzine did not reach significance until day 2 (p = 0.001). Compared with patients who received placebo, patients who received cetirizine and those who received hydroxyzine showed reductions during weeks 1, 2, and 3 and at end-point analysis in the number and size of lesions and in the severity of pruritus (p < 0.04). Patient and physician evaluations at the end of week 4 revealed an improvement in urticarial symptoms for the hydroxyzine and cetirizine groups compared with the placebo group (p < 0.001). Four patients in the hydroxyzine group, 1 patient in the cetirizine group, and 1 patient in the placebo group discontinued the study because of sedation. No patient withdrew because of lack of efficacy. CONCLUSIONS: Cetirizine 10 mg once daily was equivalent to hydroxyzine 25 mg tid in controlling the symptoms of patients with chronic urticaria, as assessed by patient and investigator evaluations.
Selegiline in Treatment of Behavioral and Cognitive Symptoms of Alzheimer Disease
Authors: Tolbert Sandra R. , Fuller Matthew A. 
Published: January 2017

OBJECTIVE: To evaluate the effects of selegiline on behavioral and cognitive symptoms of patients with Alzheimer disease. DATA SOURCES: An English-language MEDLINE search (1982–1995) was used to identify the review articles and human clinical trials discussed in this article. STUDY SELECTION: Double- and single-blind and open-label trials were reviewed. Studies were also reviewed if selegiline was evaluated comparatively with other agents. Review articles were used for background information. DATA EXTRACTION: Data were evaluated from human studies. Studies were critiqued on the basis of design, methodology, duration, sample size, and the degree to which neuropsychological tests used in each study were compared. DATA SYNTHESIS: Selegiline is a selective, irreversible inhibitor of monoamine oxidase type B. Eight of 11 controlled trials showed selegiline had a positive effect on cognition (e.g., word fluency, delayed recall, total recall). Two of 5 controlled trials evaluating selegiline's effect on behavior (e.g., anxiety, tension, excitement, depression) showed a positive effect. CONCLUSIONS: The role of selegiline remains to be determined by large well-controlled, long-term clinical trials. Selegiline may be a useful agent in managing behavioral and cognitive symptomatology associated with Alzheimer disease. Given that the management of Alzheimer disease is symptomatic and no standard treatment exists, selegiline should be considered among the various options.
Comparative Study of Bioavailability and Clinical Efficacy of Carbamazepine in Epileptic Patients
Authors: Silpakit Orawan , Amornpichetkoon Montri , Kaojarern Sming 
Published: January 2017

OBJECTIVE: To compare the bioavailability of three generic brands of carbamazepine tablets with that of a proprietary brand in adult patients with epilepsy. DESIGN: A double-blind, randomized, three-phase crossover study. SETTING: A psychiatric facility. PARTICIPANTS: Eighteen patients with epilepsy who had taken carbamazepine at least 5 months before entering the study. MAIN OUTCOME MEASURES: Ten blood specimens from each patient were collected at steady-state. Plasma concentration of carbamazepine was analyzed for pharmacokinetic parameters such as maximum plasma concentration (Cmax), mean time to reach maximum concentration (tmax), and mean AUC. RESULTS: There were no statistically significant differences in these parameters among four brands of carbamazepine. However, when comparing the 90% CI of AUC of three generic brands with that of the proprietary brand, the AUC of two generic brands lay within a range of 80% to 120%. The effects of gender and each brand of carbamazepine on these pharmacokinetic parameters were also analyzed. Breakthrough seizures occurred even though the plasma concentration of carbamazepine was therapeutic. CONCLUSIONS: The bioavailability of two generic brands of carbamazepine tablets (Carmapine and Carzepine) and the proprietary brand (Tegretol) were equivalent in this sample of adult patients with epilepsy.
Generalized Seizures Associated with the Use of Muromonab-CD3 in Two Patients after Kidney Transplantation
Authors: Seifeldin Raafat A , Lawrence Kenneth R , Rahamtulla Anisha F , Monaco Anthony P 
Published: January 2017

OBJECTIVE: TO report two cases of seizures associated with the use of muromonab-CD3. CASE SUMMARY: TWO uremic cadaveric kidney transplant recipients had developed generalized seizures following administration of muromonab-CD3 within the first 2 days after transplantation. Seizures were treated successfully with intravenous phenytoin, and muromonab-CD3 administration was discontinued. DISCUSSION: The overall frequency of seizures during muromonab-CD3 administration is 6%. Uremia in patients in the early posttransplant period appears to predispose them to seizures. Seizures that happened to our two uremic patients after transplant suggest that they had been induced by muromonab-CD3 administration. The mechanism of how this could have induced seizures is unknown. CONCLUSIONS: Prophylactic muromonab-CD3 should be used carefully in uremic kidney transplant recipients following surgery. If therapy with muromonab-CD3 is necessary, early hemodialysis should be considered in an effort to lower the risk of seizures.
Efficacy and Safety of Intravenous Phosphate Replacement in Critically Ill Patients
Authors: Perreault Marc M , Ostrop Nikola J , Tierney Michael G 
Published: January 2017

OBJECTIVE: To evaluate the efficacy and safety of intravenous potassium phosphate administered in a fixed-dose regimen in critically ill patients. DESIGN: Prospective, unblind study. SETTING: Surgical—medical intensive care unit (ICU). PARTICIPANTS: Patients who developed hypophosphatemia during their ICU admission. INTERVENTIONS: Patients with a serum phosphate concentration between 1.27 and 2.48 mg/dL (group 1) and those with a concentration of 1.24 mg/dL or less (group 2) received 15 and 30 mmol, respectively, of phosphate as a potassium salt via a central line over 3 hours. MAIN OUTCOME MEASURES: Normalization of serum phosphate within 6 hours of infusion, the development of arrhythmias during the infusion, and the development of hypocalcemia and hyperkalemia after the infusion were evaluated. Redevelopment of hypophosphatemia and the need for further therapy were also assessed. RESULTS: Thirty-seven episodes of hypophosphatemia were entered in this study: 27 in group 1 (17 patients) and 10 in group 2 (10 patients). The mean serum phosphate concentration increased significantly from 2.02 to 2.82 mg/dL in group 1 and from 0.83 to 2.17 mg/dL in group 2, with no change in calcium or potassium. Normalization of serum phosphate with this initial dose occurred in 81.5% of the episodes in group 1 and 30% in group 2. However, over the following 2 days, 45% of the patients in group 1 and 60% in group 2 required further phosphate supplementation. No arrhythmias occurred during the 3-hour infusion that were related to the potassium phosphate. A significant drop in total serum calcium concentrations occurred in 2 patients who were slightly hypercalcemic prior to the infusion. Serum calcium concentrations remained above normal, but this was not associated with any adverse effects. CONCLUSIONS: The administration of potassium phosphate 15 mmol to critically ill patients with mild-to-moderate hypophosphatemia over 3 hours is both effective and safe. The administration of potassium phosphate 30 mmol to severely hypophosphatemic patients was safe but achieved normalization of serum phosphate in a minority of patients. Either a higher dose or the subsequent administration of more potassium phosphate may be required to normalize serum phosphate concentrations. Once normalization has occurred, there is a high likelihood of redevelopment of hypophosphatemia over the following 2 days and supplementation should be given accordingly.
Severe Minocycline-Induced Eosinophilic Pneumonia: Extrapulmonary Manifestations and the Use of in Vitro Immunoassays
Authors: Bentur Lea , Bar-Kana Yaniv , Livni Ella , Finkelstein Renato , Ben-Izhak Ofer , Keidar Shlomo , Bentur Yedidia 
Published: January 2017

OBJECTIVE: To report a severe and unusual reaction to minocycline and the use of in vitro immunologic assays. CASE SUMMARY: A 46-year-old white man developed severe respiratory distress with pulmonary infiltrates on chest X-ray and eosinophilia in blood, bronchoalveolar lavage fluid, and biopsied lung tissue during exposure to minocycline. Additional manifestations included pleuropericardial effusion, liver function abnormality, and bone marrow eosinophilia. Macrophage inhibition factor and mast cell degranulation assays were positive to minocycline. DISCUSSION: The patient's manifestations were compatible with the diagnosis of eosinophilic pneumonia. After excluding other possible etiologies, minocycline was identified as the offending agent. Generalized damage was suggested by the presence of a combination of extrapulmonary manifestations previously not reported. Results of the in vitro immunologic assays supported the hypersensitivity nature of the disease and confirmed the diagnosis. CONCLUSIONS: Minocycline-induced eosinophilic pneumonia may involve extrapulmonary sites. It is suggested that in vitro immunoassays be used for confirmation of the diagnosis rather than rechallenge or invasive procedures.
Depression in Primary Care: Review of AHCPR Guidelines
Authors: Cohen Lawrence J , Guthrie Sally K 
Published: January 2017

OBJECTIVE: To present an overview and evaluation of the Agency for Health Care Policy and Research (AHCPR) clinical practice guidelines for the treatment of depression. INTRODUCTION: One responsibility of the AHCPR is the development and periodic review and update of clinical practice guidelines. This process is undertaken by an independent panel composed of groups of clinicians and other experts from the private sector. Their findings are published in a four-volume, softcover set of booklets. DATA SOURCE AND EVALUATION: Volume 2 in the four-volume set includes a comprehensive compilation, synthesis, and critical evaluation of the studies of different treatments for depression. Studies included for evaluation were randomized, prospective clinical trials that were pertinent to all topics concerning the treatment of depression. In some areas, the opinions of the panel were included due to a paucity of data from well-controlled clinical trials. Each AHCPR guideline was followed by a code that indicated whether the strength of evidence supporting that guideline was based on good or fair research-based evidence, or whether it was based primarily on panel members' opinions. CONCLUSIONS: With regard to drug treatment, the guidelines are good. However, since these guidelines were published in 1993 they might be considered somewhat dated because more antidepressants have become available in the interim. Overall, the AHCPR guidelines reflect an extensive review of the literature provided by the panel, as well as input from a highly respected group of reviewers. The panel included physicians, a nurse, a social worker, a psychologist, and a consumer representative. Unfortunately, a pharmacist was not included on the panel. Input from pharmacy practitioners would have been valuable.
Pharmacokinetics of Methotrexate in Plasma and Cerebrospinal Fluid
Authors: Morikawa Norifumi , Mori Teruaki , Abe Tatsuya , Ghoda Makoto , Takeyama Masaharu , Hori Shigeaki 
Published: January 2017

OBJECTIVE: To investigate the pharmacokinetics of methotrexate (MTX) in plasma and cerebrospinal fluid (CSF) during osmotic disruption of the blood-brain barrier and the intraarterial administration of combination chemotherapy postoperatively in a patient with glioblastoma. CASE SUMMARY: A 60-year-old Japanese woman with a glioblastoma received two courses of combination intraarterial chemotherapy. In the first course of treatment, 20 mL of mannitol 20%, peplomycin 10 mg, vindesine 2 mg, and MTX 500 mg were administered via the right internal carotid artery, and then via the right vertebral artery. In the second course of treatment, 20 mL of mannitol 20%, peplomycin 15 mg, vindesine 2.5 mg, and MTX 1000 mg were similarly administered. Blood samples and CSF samples from the ventricle and the space left by tumor removal were obtained; the MTX concentrations were measured from these sites by fluorescence polarization immunoassay. The pharmacokinetic parameters of MTX in plasma and CSF were estimated. DISCUSSION: The plasma concentration of MTX decreased in a biexponential decay pattern during each course of treatment. CSF concentrations of MTX in the ventricle and in the space left by tumor removal peaked at 2 and 6 hours, respectively, after drug administration and decreased monoexponentially. When the dose of MTX was doubled, the AUC for the plasma MTX concentration increased 2.4-fold and the AUCs for MTX in the ventricle and the space left by tumor removal increased 3.4- and 9.1-fold, respectively. The half-life of MTX in the CSF in the space left by tumor removal exceeded the half-lives of MTX in the plasma and in the ventricular CSF. CONCLUSIONS: The CSF AUCs of MTX in the ventricle and the space left by tumor removal increased markedly and in parallel with the MTX dosage increase during osmotic disruption of the blood-brain barrier and intraarterial combination chemotherapy. Such treatment improves the delivery of chemotherapy agents to the brain.
Paclitaxel-Induced Acute Bilateral Pneumonitis
Authors: Khan Amir , McNally Daniel , Tutschka Peter J , Bilgrami Syed 
Published: January 2017

OBJECTIVE: To report three cases of paclitaxel-induced acute bilateral pneumonitis, as well as to ascertain its incidence and outcome. CASE SUMMARIES: A total of 239 patients with a variety of underlying malignancies received 528 courses of paclitaxel-containing chemotherapy. Paclitaxel 200 mg/m2 was infused over 3 hours with standard premedication. Three patients developed bilateral interstitial infiltrates either during or within 6 hours of the administration of paclitaxel. Symptoms included a nonproductive cough, dyspnea, and sudden arterial oxygen desaturation. Response to parenteral corticosteroids was dramatic and reversed the process in all 3 patients. DISCUSSION: Paclitaxel-induced acute bilateral pneumonitis appears to be a rare adverse reaction. It may either be a direct toxic effect of the chemotherapeutic agent or an adverse effect of its Cremophor EL diluent. Although the exact pathophysiology is unclear, a variety of immune and nonimmune mechanisms have been postulated, including hypersensitivity reactions, release of cytokines from macrophages, and the possible role of prior thoracic irradiation. CONCLUSIONS: Acute bilateral pneumonitis occurs in less than 1% of individuals receiving 3-hour infusions of paclitaxel, and responds dramatically to parenteral corticosteroid therapy.
Ofloxacin-Lnduced Seizure
Authors: Walton Gary D , Hon Jeremy K , Mulpur Tejanand G 
Published: January 2017

OBJECTIVE: To describe a possible case of ofloxacin-induced generalized tonic—clonic seizure. Although the etiology is unknown, ofloxacin most likely precipitated this patient's seizure threshold because of sepsis or secondary to drug accumulation due to the patient's compromised renal function. CASE SUMMARY: A 69-year-old white woman with non-small-cell lung cancer and a history of central nervous system metastatic disease treated with radiation therapy presented to the emergency department with symptoms of urosepsis. Because of multiple drug allergies she was started on ofloxacin (hospital formulary quinolone). After 4 days of therapy she developed a generalized tonic—clonic seizure. A computed tomography scan of the head with and without contrast was negative. The ofloxacin was discontinued and aztreonam therapy was started. Phenytoin therapy was instituted and, despite serum concentrations below the conventional therapeutic range, there was no recurrence of seizure. Subsequent discontinuation of phenytoin did not result in a seizure for this patient. DISCUSSION: Seizures induced by the fluoroquinolones are uncommon. The histopathologic features of this phenomenon are currently unknown. In this patient, imaging studies were negative for structural defects, ruling out metastasis as the cause of the seizure. Therefore, an investigation of drug-related causes ensued. The most likely offending agent was ofloxacin. Ofloxacin has been reported in the literature as a cause of seizures in patients with compromised renal function. CONCLUSIONS: This case and other reports indicate that fluoroquinolones, including ofloxacin, may contribute to seizure development in patients with or without a history of epilepsy. Fluoroquinolone therapy should be used with caution in patients with risk factors for the development of drug-induced seizures.
Extrapyramidal Reactions and the Selective Serotonin-Reuptake Inhibitors
Authors: Caley Charles F 
Published: January 2017

OBJECTIVE: To review the known published reports of extrapyramidal reactions (EPRs) associated with the use of selective serotonin-reuptake inhibitors (SSRIs). DATA SOURCES: Information was selected from a MEDLINE search (January 1990 to January 1996) of English-language medical literature. Manual searches of pertinent journal article bibliographies were also performed. DATA EXTRACTION: Appropriate information from all reports obtained was included, with specific attention directed toward patient age, gender, primary psychiatric diagnosis, total daily SSRI dosage, dosage escalation strategy, and concurrent psychotropic medications. DATA SYNTHESIS: Reports of EPRs associated with SSRI use have been accumulating in the medical literature for several years. More commonly associated with high-potency antipsychotics, EPRs can have an adverse impact on medication compliance and hospital readmissions. The proposed hypothesis for EPRs occurring with SSRI use involves serotonin's inhibitory actions on extrapyramidal dopamine activity. Other possible contributing factors include pharmacokinetic interactions or drug—disease interactions. EPRs may include dystonias, dyskinesias, akathisia, parkinsonism, exacerbations of Parkinson's disease, and possibly the neuroleptic malignant syndrome. The majority of SSRI-related reactions appear to occur within the first month of treatment. Information from available case reports does not strongly support any consistent risk factor, although some worth considering may include total SSRI daily dose, rapid dose escalation strategies, increased age, female gender, concurrent psychotropics known to also precipitate EPRs, and concurrent disease states such as Parkinson's disease. Since SSRI-related EPRs have occurred in different situations with different possible contributing factors, clinical pharmacy practitioners and other healthcare providers should remain aware of these reactions and carefully consider educating and monitoring their patients accordingly. CONCLUSIONS: The use of SSRIs may be associated with the development of EPRs; therefore, appropriate monitoring should be considered for patients so that optimal pharmaceutical care may be provided.