bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipoprotein(A): Physiologic Function, Association with Atherosclerosis, and Effects of Lipid-Lowering Drug Therapy
Authors: Spinler Sarah A. , Cziraky Mark J. 
Published: January 2017

OBJECTIVE: To review the structure and physiologic function of liipoprotein(a) [Lp(a)], review the association of Lp(a) with the development of atherosclerosis, and to critically evaluate the current literature regarding the effects of lipid-lowering drug therapy on Lp(a) serum concentrations. DATA SOURCES: English language clinical and animal studies, abstracts, and review articles pertaining to Lp(a). STUDY SELECTION AND DATA EXTRACTION: Relevant human and animal studies examining Lp(a)'s role in atherosclerosis and the effect of drug therapy on Lp(a) serum concentrations. DATA SYNTHESIS: Possible physiologic functions and potential atherogenic mechanisms of Lp(a) are discussed. Evidence supporting the association of Lp(a) with atherosclerosis is presented. Studies evaluating the effects of lipid-lowering drug therapy on Lp(a) concentrations are reviewed and critiqued. CONCLUSIONS: Lp(a) concentrations are correlated with the risk of atherosclerotic vascular disease (AVO) in both animal models and human studies. Drug therapies that have produced a consistent reduction in Lp(a) concentration include niacin alone or in combination with a bile acid sequestrant or neomycin. However, additional, larger studies are needed to evaluate the ability of drug therapies to specifically reduce elevated Lp(a) concentrations. Preliminary information suggests that reduction in Lp(a) concentrations may be associated with atherosclerotic plaque regression. Although drugs are available to lower Lp(a), one cannot conclude that lowering of Lp(a) is warranted until clinical trials demonstrating beneficial effects have been published.
Fluorouracil Cardiotoxicity
Authors: Anand Ajay J. 
Published: January 2017

OBJECTIVE: To review the clinical manifestations, postulated mechanisms, and therapeutic implications of fluorouracil-induced cardiac toxicity. DATA SOURCE: A MEDLINE search was used to identify pertinent literature. STUDY SELECTION: Studies and case reports on fluorouracil cardiotoxicity were identified through a MEDLINE search. A manual review of bibliographies of identified articles was performed to ensure that all pertinent articles were included. DATA EXTRACTION: Data pertaining to all aspects of fluorouracil cardiac toxicity, including pathogenesis, predisposing factors, clinical manifestations, and therapeutic implications, were evaluated. DATA SYNTHESIS: Estimates from large series suggest a 1.6–2.3 percent incidence of clinically demonstrated cardiotoxicity. Predisposing factors include the presence of coronary artery disease and concurrent radiotherapy. Postulated mechanisms include direct myocardial ischemia, coronary spasm, or cardiotoxic impurities in fluorouracil formulation, Clinical manifestations include chest pain, nausea, diaphoresis with typical ischemic electrocardiographic (ECG) changes, relieved to normal after stopping the drug therapy. Nitrates and calcium-channel blockers do not protect against cardiotoxicity. CONCLUSIONS: Fluorouracil cardiotoxicity may be much more common and clinically significant than previously thought. A high index of suspicion for cardiotoxicity must be maintained when the drug is administered, especially in the presence of heart disease and concomitant radiation therapy. In the presence of chest pain, it is mandatory to stop the infusion and, if possible, to replace fluorouracil with another chemotherapeutic agent.
Meropenem: A New Carbapenem Antimicrobial
Authors: Pryka Randy D. , Haig George M. 
Published: January 2017

OBJECTIVE: To describe and then compare an investigational carbapenem antibiotic, meropenem, with the only currently available antibiotic in this class, imipenem/cilastatin. DATA IDENTIFICATION: An English language search using MEDLINE (1988–1993); Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), 1991; and Abstracts of the 32nd ICAAC, 1992. STUDY SELECTION: All current scientific publications were reviewed for study design and quality. Emphasis was placed on susceptibility and pharmacokinetic analysis. Phase 3 clinical trials are now being completed and have only been published in abstract form. Hence, conclusions derived regarding efficacy were tempered. RESULTS: Meropenem is active against a broad spectrum of gram-positive and -negative pathogens including beta-lactamase producers. Meropenem appears to be two- to fourfold less active than imipenem against gram-positive organisms. Meropenem is two- to fivefold more active against enterobacteriaceae. The two compounds appear to be equally active against Pseudomonas aeruginosa. Pharmacokinetic disposition is also similar for imipenem and meropenem. Meropenem may exhibit greater tissue penetration. Meropenem is not labile to renal hydrolysis and can be administered without a competitive antagonist of dihydropeptidase, such as cilastatin. In clinical trials, meropenem appears to be as safe and effective as imipenem/cilastatin or ceftazidime in the treatment of infections involving soft tissue, urinary tract, upper respiratory tract, abdominal processes, and febrile neutropenic episodes. CONCLUSIONS: Meropenem is comparable to imipenem in terms of in vitro susceptibility pattern and pharmacokinetic disposition. Overall, meropenem seems to offer promise as the second of the carbapenem class of antibiotics. Clinical data are preliminary, and further data are needed.
Malabsorption of Digoxin Tablets, Gel Caps, and Elixir in a Patient with an End Jejunostomy
Authors: Ehrenpreis Eli D. , Guerriero Stephanie , Nogueras Juan J. , Carroll Maria A. 
Published: January 2017

OBJECTIVE: To report a case of malabsorption of digoxin from tablets, gel caps, and elixir in a patient with an end jejunostomy. CASE SUMMARY: A 69-year-old man with 18 cm of functioning jejunum following a surgical end jejunostomy was receiving oral digoxin. The patient presented on referral for short bowel syndrome, secretory diarrhea, and malabsorption. He was receiving digoxin tablets 0.75 mg/d with a serum digoxin concentration of 0.5 ng/mL. Attempts to achieve therapeutic digoxin serum concentrations of approximately 1.0 ng/mL by administration of digoxin in the form of liquid-filled gel caps and elixir were unsuccessful. DISCUSSION: Variable results have been presented in the literature regarding the ability to achieve therapeutic concentrations of digoxin following oral administration in patients with malabsorption syndromes. Several studies have suggested that changing the form of administered digoxin from tablet to elixir or liquid-filled gel caps may improve absorption in patients with small intestine malabsorption. Such changes in oral dosage form failed to achieve therapeutic digoxin serum concentrations in this case. CONCLUSIONS: The markedly diminished length and the lack of continuity of this patient's small intestine and colon likely resulted in severe malabsorption of orally administered digoxin. Some patients with end jejunostomies may require intravenous forms of medication because of inadequate absorption of orally administered medications.
Management of Bacterial Urinary Tract Infections in Adults
Authors: Hatton Jimmi , Hughes Melody , Raymond Claire H. 
Published: January 2017

OBJECTIVE: To provide a comprehensive review of the diagnosis and therapeutic management considerations in patients with urinary tract infections (UTIs). DATA SOURCES: A MEDLINE search was used to identify pertinent English language literature, including reviews. Infectious disease textbooks were used for background information. STUDY SELECTION: Clinical trials evaluating drug therapy in a variety of patient populations with UTIs were reviewed. DATA EXTRACTION: Background information was obtained from comprehensive reviews. Drug dosing strategies and efficacy comparisons were extracted from the investigations in this area. DATA SYNTHESIS: Information was processed to provide general guidelines and resources for practitioners to use in managing UTIs. CONCLUSIONS: There are a number of useful antibiotics for the management of UTIs. The distinctions between infection severity and underlying risk factors within a given population influence the appropriateness of drug selection and duration of treatment.
Meta-Analysis of Controlled Trials of Drug Therapy in Mild Chronic Asthma: The Role of Inhaled Corticosteroids
Authors: Milavetz Gary , Kelly H. William , Hatoum Hind T. , Schumock Glen T. , Kendzierski Donald L. 
Published: January 2017

OBJECTIVE: To determine the role of inhaled corticosteroids in the treatment of mild chronic asthma. SOURCE OF STUDIES: Searches of MEDLINE and Index Medicus for English language literature dealing with asthma and inhaled corticosteroids. DESIGN: All retrieved articles were subjected to predetermined criteria for inclusion in the meta-analysis. Inclusion criteria centered around randomized, double-blind studies reporting objective clinical endpoint(s) for subjects with mild chronic asthma who were treated for more than seven days. Studies that were included were not allowed to have any predetermined exclusion criteria. RESULTS: The literature search identified 129 articles, of which 41 satisfied some but not all of the criteria for inclusion. Five articles met all the criteria and were subjected to meta-analysis. The total number of subjects was 141. Peak expiratory flow rate (PEFR) was used as the objective endpoint for effect size calculation. Subjecting these five studies to quality review revealed a range of 0.607–0.741, with 1 as the highest attainable quality and 0 the lowest. Reported results for the different studies were found to be homogenous, thus allowing for the calculation of overall effect size. Inclusion of children in some of the studies added variance to the reported studies, but not to the point at which studies would be considered heterogenous. Effect sizes ranged between 0.41 and 0.89, and the overall weighted average effect size for PEFR was 0.59, with the calculated 95 percent confidence interval at 0.32 to 0.84. A tabulated display of binomial effect size for included trials provided ranges of success rates for treatment versus control values. Results of the studies were judged robust, as 92 studies reporting no significant effects are needed to turn the finding of the meta-analysis insignificant. CONCLUSIONS: Based on the results of the meta-analysis, the existing literature suggests a role for inhaled corticosteroids in the treatment of mild chronic asthma.
Probable Ticlopidine-Induced Cholestatic Hepatitis
Authors: Cassidy L. Jane , Schuster Brenda G. , Halparin Lawrence S. 
Published: January 2017

Objective: To report a case of probable ticlopidine-induced cholestatic hepatitis. Case summary: A 76-year-old man with no known history of liver disease developed painless jaundice approximately 3 weeks after starting ticlopidine 250 mg bid. After ticlopidine was discontinued, the jaundice resolved and serum liver enzyme concentrations returned toward normal. A diagnosis of probable ticlopidine-induced cholestatic hepatitis was made. The patient was not rechallenged with ticlopidine. Discussion: A literature search produced 6 case reports describing 7 patients in whom probable ticlopidine-induced cholestatic hepatitis had been diagnosed. Only 1 of these reports appeared in the North American literature. Jaundice developed within 1 to 3 months of starting ticlopidine at less than or equal to the recommended daily dose. In all cases, jaundice resolved and serum liver enzyme concentrations normalized over a period of months after drug discontinuation. Conclusions: Routine monitoring of serum liver enzyme concentrations is not recommended. However, patients should be instructed to watch for signs and symptoms of liver injury. Should they occur, patients should stop taking the ticlopidine and consult their physician immediately.
Suspected Ciprofloxacin-Induced Hepatotoxicity
Authors: Villeneuve Jean-Pierre , Davies Campbell , Côté Jean 
Published: January 2017

Objective: To report a case of probable ciprofloxacin-induced hepatotoxicity. Case Summary: A 44-year-old woman developed severe hepatitis 3 weeks after initiation of a 7-day course of oral ciprofloxacin therapy. Liver biopsy showed severe hepatic necrosis, and other causes of liver injury were excluded. Liver function test results returned to normal 4 months after the appearance of jaundice. Discussion: The time course of events suggested that ciprofloxacin was the cause of severe hepatitis in this patient, and other causes of hepatitis were ruled out. Hepatotoxicity has been reported with other fluoroquinolone antibiotics, and there have been previous unpublished reports to the manufacturer of possible hepatotoxicity caused by ciprofloxacin. Conclusions: It is suggested that ciprofloxacin can cause severe hepatic injury and that healthcare providers should be aware of this possible adverse drug reaction.
Amphotericin B Toxicity Reduced by Administration in Fat Emulsion
Authors: Anderson Robert P , Clark Douglas A 
Published: January 2017

Objective: To report a patient with intolerance to amphotericin B reversed by preparing the antifungal in fat emulsion 20% and to review the medical literature on innovative formulations of amphotericin B. Case Summary: A 51-year-old man diagnosed with acute myelogenous leukemia was treated with standard induction chemotherapy. Empiric antibiotic therapy was initiated 2 days postchemotherapy; however, the patient continued to be febrile until day 7. At this time amphotericin B 35 mg/250 mL D5W over 4 hours was administered. Despite premedication, the patient experienced severe rigors, chills, and fever. As the result of continuing infusion-related adverse events, the patient refused further therapy after the third daily dose. In an attempt to reduce the infusion-related events, a trial of amphotericin B 35 mg/35 mL of fat emulsion 20% was administered over 2 hours after patient consent was obtained. Premedication was administered and the patient tolerated therapy without adverse events. Amphotericin B dosage escalations to 50 and 70 mg were tolerated similarly. During this treatment the patient became afebrile and the serum creatinine concentration decreased to normal. Discussion: Despite significant toxicities and the development of newer antifungal agents, amphotericin B remains the drug of choice for the empiric coverage of suspected fungal infection in neutropenic patients. Amphotericin B often exacerbates the nephrotoxicity of other agents characteristically prescribed in these patients. Furthermore, infusion-related events, if not intolerable, can dramatically reduce the patient's quality of life. For these reasons, novel means of amphotericin B administration are being explored. Conclusions: The delivery of amphotericin B in a lipid diluent may have substantial benefit in reducing the nephrotoxicity and infusion-related events associated with the antifungal. Prospective clinical trials comparing lipid-complexed amphotericin B with liposomal and approved formulations of amphotericin B are essential to define potential differences in toxicity and efficacy.
Water Handling In Patients Receiving Haloperidol Decanoate
Authors: Rider Joan M , Mauger Theodore F , Jameson John P , Notman Douglas D 
Published: January 2017

Objective: To determine whether water handling in patients receiving haloperidol decanoate (HD) was impaired. Design: Prospective, controlled trial of water handling in patients without symptomatic hyponatremia receiving HD. Eligibility for study inclusion required that patients had received HD for at least 4 months, were not taking any medication reported to cause inappropriate antidiuretic hormone secretion or hyponatremia (excluding haloperidol), and would agree to participate in the study. An age- and gender-matched healthy control subject was enrolled for each study patient. Baseline laboratory values were obtained within 48 hours prior to the standard water-loading test to screen for abnormalities in electrolytes, kidney function, and liver function. A 20-mL/kg water-load test was administered to each patient. Urine volume and osmolality were measured every hour for 4 hours. Setting: A community mental health (CMH) outpatient psychiatric facility for the patients receiving HD and Saint Mary's Health Services for the controls. Participants: Fifteen patients receiving HD from the CMH facility and 15 age- and gender-matched control subjects were enrolled. Main Outcomes Measures: Impaired water handling was defined as a failure to dilute urine to less than 100 mmol/kg or a failure to excrete more than 65% of a water load in 4 hours. Results: Five patients receiving HD were excluded because of protocol refusal or violation. Five of 10 evaluable patients receiving HD had abnormal water handling. Two of these could not lower their urine osmolality to less than 100 mmol/kg, 2 could not excrete more than 65% of the water load, and 1 did not meet either criteria. None of the healthy volunteers had abnormal free water handling. The difference between the study patients and the control subjects was statistically significant (p = 0.0097). Conclusions: Fifty percent of our study patients receiving HD had abnormal free water handling. This finding, combined with our clinical observations of symptomatic hyponatremia in other patients receiving the drug, suggests the need to investigate the incidence of hyponatremia and to design a useful screening tool to identify patients at risk. In the meantime, clinicians should be aware of the potential for impaired water handling in patients receiving HD.
Gastrointestinal Complications Associated with Intramuscular Ketorolac Tromethamine Therapy in the Elderly
Authors: Maliekal James , Elboim Charles M 
Published: January 2017

Objective: To report 3 cases of gastrointestinal (GI) complications associated with the use of intramuscular ketorolac tromethamine therapy in elderly patients. Case Summaries: In case 1, an 88-year-old woman was taken to surgery for the management of an acute abdomen and repair of a 2+ cm perforated prepyloric gastric ulcer. The patient had received a total 16 doses of ketorolac 30 mg im. The patient died after surgery from complications associated with bacterial and candidal sepsis, as well as acute renal failure. In case 2, an 80-year-old woman with no known history of GI problems developed a prepyloric gastric ulcer, which perforated and penetrated into the pancreas after the patient received 13 doses of ketorolac 30 mg im. The patient died from complications associated with candidal sepsis, peritonitis, and cardiopulmonary collapse. In case 3, an 85-year-old man with a history of a gastric ulcer developed GI bleeding after receiving a total of 9 doses of ketorolac 30 mg im. The bleeding was stabilized and the patient was discharged 12 days later in stable condition. Discussion: Ketorolac tromethamine is a nonsteroidal antiinflammatory drug with potent analgesic properties. We report 3 cases of GI complications associated with intramuscular ketorolac therapy in the elderly. A temporal relationship was established with the development of gastric ulceration in 2 patients and the recurrence of a gastric ulcer in the third patient. Conclusions: We recommend that the manufacturer's guidelines be followed when ketorolac is used in elderly patients, and the drug should not be used in patients with a history of gastric ulcer disease. The use of misoprostol may be warranted as prophylactic therapy in high-risk patients who are receiving ketorolac.
Desogestrel, Norgestimate, and Gestodene: The Newer Progestins
Authors: Kaplan Barbara 
Published: January 2017

Objective: To review and compare the newer progestins desogestrel, norgestimate, and gestodene with regard to chemistry, pharmacokinetics, efficacy, and tolerability. Data Sources: Primary literature on desogestrel, norgestimate, and gestodene was identified from a comprehensive MEDLINE English-literature search from 1984 through 1994, with additional studies selected by review of the references. Indexing terms included progestins, desogestrel, gestodene, norgestimate, levonorgestrel, and norgestrel. Study Selection: Only human clinical and pharmacokinetic trials performed in Europe, Canada, and the US were included. Data Extraction: All available data from human studies were reviewed; both comparative and noncomparative studies were included because of the paucity of direct comparative information available. Data Synthesis: The newer progestins were designed to minimize the adverse effects (e.g., acne, hirsuitism, nausea, carbohydrate and lipid metabolism changes) observed with older oral contraceptives (OCs) while maintaining efficacy and good menstrual cycle control. Desogestrel, norgestimate, and gestodene have minimal amounts of androgenicity and antiestrogenic potential. All of these agents are pharmacokinetically similar to older agents: they are highly bioavailable when administered orally, hepatically metabolized, and obtain steady-state concentrations after 8-10 days of continuous administration. The newer agents have similar Pearl Indexes and slightly better cycle control. Furthermore, the new progestins appear to cause fewer adverse effects, such as acne and hirsuitism, and similar rates of weight gain, blood pressure changes, and lipid and carbohydrate metabolism changes. Conclusions: Desogestrel, norgestimate, and gestodene appear to offer clinical advantages because of their decreased androgenicity. Women whose cycles are currently well controlled with other OCs should not be switched to a newer progestin. However, any of the combination OC products that contain these progestins may be prescribed for women intolerant of older agents or to first-time users of OCs. The newer progestins appear to be efficacious and offer similar cycle control, improved safety and tolerability profiles, and comparable price with the older agents.
Changing Physician Behavior in Ordering Digoxin Assays
Authors: Fraser Gilles L , Wennberg David E , Dickens John D , Lambrew Costas T 
Published: January 2017

OBJECTIVE: TO assess the ability to modify physicians' use of serum digoxin assays in a sustained fashion through (1) an educational intervention by a clinical pharmacist, and (2) changes in the computerized medical information system. DESIGN: A before/after methodology was used to compare test use by hospital staff physicians in two phases. Phase 1 was an educational intervention conducted by a clinical pharmacist with an 8-month follow-up. Phase 2 was a medical information system intervention with a 12-month follow-up. PATIENTS: Adult inpatients from July 1990 through December 1993 who received either digoxin therapy or at least one serum digoxin assay. MAIN OUTCOME MEASURE: Digoxin assays per patient day while receiving digoxin (assays/digoxin day), in-hospital mortality, and length of stay were compared before and after implementation of the interventions. RESULTS: A total of 9468 patients received a digoxin and/or serum digoxin assay. Baseline use of serum digoxin assays was 0.178 assays/digoxin day. Following phase 1, the educational intervention, use declined 20.2% to 0.142 assays/digoxin day (p < 0.03). After phase 2, the implementation of changes in the medical information system, digoxin assay use was maintained at 16.3% less than that at baseline (p < 0.03). Patient mortality was unaffected. CONCLUSIONS: A low-intensity educational intervention by a clinical pharmacist supplemented by medical information system modification resulted in an important decrease in the use of digoxin assays. The change in physician behavior was sustained for more than 18 months. The model presented is not labor intensive, does not require continuous maintenance by healthcare personnel for a sustained effect, and may be widely applicable to healthcare providers.