bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clarithromycin: Review of a New Macrolide Antibiotic with Improved Microbiologic Spectrum and Favorable Pharmacokinetic and Adverse Effect Profiles
Authors: Sturgill Marc G. , Rapp Robert P. 
Published: January 2017

OBJECTIVE: To compare the new macrolide antibiotic clarithromycin with erythromycin in terms of in vitro activity, pharmacokinetics, pharmacodynamics, clinical efficacy, and toxicity. DATA IDENTIFICATION: An English-language literature search employing MEDLINE (1987–91), Index Medicus (1987–91), Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy (1990), Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy (1991), and bibliographic reviews of related textbooks and review articles. STUDY SELECTION: Eighty-five articles were selected. Clinical trials with clarithromycin have been limited, and emphasis was placed on trials reported in the Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy and Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy. DATA EXTRACTION: Articles were assessed for study quality and specific information addressing the stated purpose. In articles reporting the results of clinical trials, emphasis was placed on comparative efficacy and toxicity. RESULTS OF DATA ANALYSIS: A review of 24 human trials suggests that clarithromycin is equally effective as erythromycin, penicillin VK, ampicillin, or amoxicillin for treatment of a variety of upper and lower respiratory tract or skin infections. Clarithromycin also appears to be better tolerated than these agents, with a lower incidence of gastrointestinal adverse effects. Limited clinical studies in patients with Mycobacterium leprae or Mycobacterium aviumintracellulare complex (MAI) suggest that clarithromycin may prove to be efficacious and well tolerated in the treatment of these infections. CONCLUSIONS: Clarithromycin is as effective in vivo as erythromycin, with less gastrointestinal irritation. Additionally, clarithromycin appears to expand the traditional spectrum of macrolide antibiotics, with promising activity against M. leprae and MAI.
Implications of the Study Population in the Early Evaluation of Anticholinesterase Inhibitors for Alzheimer's Disease
Authors: Cutler Neal R. , Sramek John J. , Murphy Michael F. , Nash Ralph J. 
Published: January 2017

OBJECTIVE: Velnacrine testing for tolerance and safety in both normal elderly subjects and patients with Alzheimer's disease (AD) is reviewed to illustrate the importance of Phase I trials in the target group as more predictive of safety and tolerance for subsequent multicenter trials than those conducted in healthy elderly subjects. DESIGN: Both a single-dose and a randomized, double-blind, placebo-controlled, ascending, multiple-dose study were performed with healthy, elderly men. In the multiple-dose study, the subjects were randomized to four groups of 14, with 10 subjects receiving velnacrine and 4 receiving placebo. The doses were velnacrine 25 (group 1), 50 (group 2), and 100 mg (group 3), respectively, administered twice daily; group 4 received 100 mg three times daily for 28 days. Blood and urine were collected serially for the pharmacokinetic assessment. With AD patients, 24 subjects were randomly assigned to receive either placebo or velnacrine for 10 days in a double-blind, sequential escalation study in a hospital setting. There were three groups of 8 subjects. Six patients in each group received velnacrine and 2 placebo. The three groups received respective dosages of 450, 300, and 225 mg/d three times daily. Adverse events were closely monitored and recorded. PATIENTS/PARTICIPANTS: The multiple-dose test in healthy elderly men included 56 men, aged 60–74 years. Rigorous screening for any potential complications that could affect absorption, distribution, metabolism, or excretion preceded patient entry in the AD patient study. Patients with a history of major psychiatric, neurologic, and cardiovascular disorders were excluded. The patients ranged in age from 56 to 89 years, and were equally distributed between gender. INTERVENTION: Velnacrine was administered in various doses. MAIN OUTCOME MEASURES: We emphasize the extreme adverse effects encountered in the AD patient group compared with the healthy group. Plasma concentrations of velnacrine over time in both groups are given, as well as the drug's half-life and excretion rates. RESULTS: The tolerable dosage predicted by studies performed in healthy elderly subjects was 300 mg/d. This dosage was not tolerable among the AD patients. A dosage as high as 450 mg/d resulted in a tonic seizure in one patient. The predicted dosage of 300 mg/d produced an adverse effect profile in AD patients that included dizziness, nausea and/or vomiting, headaches, and severe diarrhea. AD patients tolerated a dosage of 225 mg/d. CONCLUSIONS: A velnacrine dosage of 300 mg/d that was tolerated in healthy elderly subjects was not tolerated by AD patients.
Serum Albumin Concentrations: Who Needs Them?
Authors: Erstad Brian L. 
Published: January 2017

OBJECTIVE: To examine the multiple factors that influence serum albumin concentrations and to discuss settings in which the monitoring of such concentrations provides clinically useful information. DATA SOURCES: Original investigations, review articles, books, and abstracts published in English. STUDY SELECTION: Studies pertaining to factors affecting serum albumin concentration were chosen based on general applicability. Recommendations related to the appropriate monitoring of albumin concentrations were based on studies performed in the clinical setting with direct applicability to patient care. DATA EXTRACTION: Data on factors affecting serum albumin concentration were extracted from studies that resulted in similar conclusions regardless of assay technique. Appropriate indications for albumin monitoring were derived from studies demonstrating direct clinical relevance. DATA SYNTHESIS: A number of factors may influence serum albumin concentration and ultimately affect interpretation of the concentration. Serum albumin concentrations generally are useful in the institutional setting shortly after admission or preoperatively to determine patient prognosis. Albumin concentrations have limited merit for predicting the free fractions of various hormones, electrolytes, and drugs. When used as an indicator of nutritional support, albumin concentrations are most helpful when measured over longer periods in relatively stable patients. CONCLUSIONS: Serum albumin determinations should be limited to those situations in which the concentrations are likely to provide clinically useful information. Such situations are limited.
Using Memory for Pain in Analgesic Research
Authors: Babul Najib , Darke Andrew C. , Johnson Donald H. , Charron-Vincent Karen 
Published: January 2017

OBJECTIVE: To determine the validity of pain intensity recall at 24 and 48 hours as a substitute for hourly pain assessments in repeated-dose analgesic studies. SETTING: Orthopedic unit of an acute care teaching hospital. PARTICIPANTS: Eighty-four patients undergoing arthroscopic reconstruction of the anterior cruciate ligament, using the patellar tendon, who were participating in a randomized, double-blind, parallel-group analgesic study. INTERVENTIONS: Patients rated their pain intensity every hour (while awake) for 48 hours and their recall of worst, least, and usual pain intensity at 24 and 48 hours using a visual analog scale (VAS). MAIN OUTCOME MEASURES: This study examined the relationship between recall of worst, least, and usual pain intensity at 24 and 48 hours and the experienced maximum, minimum, and mean pain intensity VAS scores obtained from hourly assessments over the 0–24- and 0–48-hour periods, respectively. The significance of differences between recalled and experienced pain intensity variables was assessed. RESULTS: Worst, least, and usual pain recall at 24 and 48 hours were highly correlated with experienced maximum, minimum, and mean pain from hourly reports, respectively, over the 0–24- and 0–48-hour periods (Pearson correlation coefficients, r=0.80–0.89, p<0.0001). Among the three pain recall variables, usual pain showed the highest correlation with hourly measurements. There were no significant differences between recalled pain and the corresponding measures of pain from the hourly VAS scores, except in the case of 48-hour recall of worst pain (Student's t-test, p=0.001). CONCLUSIONS: The close agreement between actual pain experience and recall of pain provides support for the use of pain recall in assessing analgesic efficacy in clinical trials.
Apparent Valproic Acid Neurotoxicity in a Hypoalbuminemic Patient
Authors: Gidal Barry E. , Collins D. Michael , Beinlich Brad R. 
Published: January 2017

OBJECTIVE: To report a case of possible neurotoxicity caused by markedly elevated free valproic acid (VPA) plasma concentrations. CASE SUMMARY: A patient with a history of a mixed-type seizure disorder that had been treated with oral VPA 1000 mg four times daily for the previous two years was admitted to the neurology service with the chief complaint of increasing difficulty in walking and involuntary muscle jerks that were new in onset. The patient was hypersomnolent and dysarthric. The total plasma VPA concentration was 103 μg/mL, which was only slightly above the recommended therapeutic range (50–100 μg/mL). VPA free fraction and free plasma concentrations, however, were unexpectedly elevated (26 percent, 26.8 μg/mL, respectively). Further laboratory evaluation revealed a serum albumin concentration of 33 g/L. The neurologic symptoms resolved upon VPA dosage reduction. DISCUSSION: VPA displays concentration-dependent protein binding, resulting in disproportionate increases in drug free fraction with increasing drug concentration. This effect may be magnified in patients with decreased plasma protein-binding capacity. The plasma protein-binding kinetics of VPA are reviewed and the implications for therapeutic drug monitoring are discussed. CONCLUSIONS: It is likely that the markedly elevated free VPA plasma concentrations contributed to the neurologic symptoms displayed in this patient. In patients with decreased albumin concentrations, failure to recognize concentration-dependent protein binding, as well as exclusive reliance upon total drug concentrations, may lead to erroneous pharmacokinetic and therapeutic interpretations.
Maternal Noncompliance with Antibiotics during Breastfeeding
Authors: Ito Shinya , Koren Gideon , Einarson Thomas R. 
Published: January 2017

OBJECTIVE: To determine the incidence of antibiotic prescription failure in breastfeeding women, and to characterize breastfeeding patterns during antibiotic therapy. DESIGN: Prospective cohort study by telephone follow-up of 203 breastfeeding women who were prescribed antibiotics as monotherapy. SETTING: A teratogen/drug information service (the Motherisk Program) in a tertiary care, pediatric hospital in Toronto, Canada. MAIN OUTCOME MEASURES: Number of breastfeeding women who did not initiate the antimicrobial therapy, and breastfeeding patterns during therapy in women who started it. RESULTS: Of 203 breastfeeding women who consulted the Motherisk Program for information about the safety of antimicrobials during breastfeeding, 125 (62 percent) were followed within 32 weeks (median 11). Nineteen of the 125 (15 percent) did not initiate the antimicrobial therapy. Of the remaining 106 women, 7 (7 percent) stopped breastfeeding during therapy. Despite reassuring advice, 1 in 5 women either did not initiate therapy or did not continue breastfeeding. CONCLUSIONS: Physicians should be aware of the substantial rate of noncompliance with drug regimens among nursing women and the potential negative impact of drug therapy on breastfeeding.
Antifungal Prophylaxis in Immunocompromised Hosts
Authors: Reents Stan , Goodwin S. Diane , Singh Vipul 
Published: January 2017

OBJECTIVE: To review the literature on the efficacy and safety of antifungal agents for prophylaxis of fungal infections in populations of immunocompromised hosts (key words: hematology-oncology, surgical, solid organ transplant, HIV infection), and to develop guidelines and recommendations regarding safe and effective drug regimens for antifungal prophylaxis in this patient population. DATA EXTRACTION: Comprehensive review of clinical trials of antifungal prophylaxis published in the English literature, with an emphasis on controlled trials, and discussion of key clinical trials illustrating efficacy and safety of agents for antifungal prophylaxis in immunocompromised patients. RESULTS: Much of the clinical data evaluating the efficacy and safety of antifungal prophylaxis has been generated in cancer patients. The choice of antifungal agent for prophylaxis in this population remains controversial. However, azole compounds such as clotrimazole, ketoconazole and fluconazole appear to be more effective and better tolerated than nystatin suspension. Although ketoconazole has been shown to reduce fungal colonization in surgical patients, current data do not support the routine use of antifungal prophylaxis in this population. In renal transplant recipients, clotrimazole troches have been shown to be more effective than placebo or nystatin suspension. Selective bowel decontamination with nonabsorbable antibiotics and nystatin may be useful in reducing Candida colonization in liver transplant patients but no definitive recommendations may be made at this time regarding optimal antifungal prophylaxis in these patients. In patients with advanced HIV disease or history of prior fungal disease prophylaxis for oropharyngeal candidiasis is indicated, although the agent of choice remains controversial. Fluconazole is the drug of choice for prevention of relapse of cryptococcal meningitis in patients with AIDS. Finally, only limited data exist assessing the relationship between local colonization and systemic fungal infection. Adverse effects associated with antifungal prophylaxis, generally limited to nausea and vomiting and transient elevations in hepatic transaminases, occur with similar frequency among available oral or topical agents. However, the incidence of nausea and vomiting with resultant poor patient tolerance and compliance is usually higher with nystatin. CONCLUSIONS: Based on available data from controlled clinical trials, azole agents are currently the most effective and best-tolerated drugs for antifungal prophylaxis in immunocompromised hosts. Choice of one agent in this group over another may be dictated by cost. As new antifungal treatments are released onto the market, these drugs should be compared with existing agents in controlled clinical trials. Future studies should be designed to evaluate the relationship between local colonization and disseminated infection.
Beta-Agonists in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: Dasta Joseph F. , Kuhl David A. , Agiri Olakunbi A. , Mauro Laurie S. 
Published: January 2017

OBJECTIVE: To critically evaluate the following issues regarding the use of beta-agonists in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD): (1) optimal dose, (2) use of nebulizer (NEB) versus metered-dose inhaler-spacer devices (MDISs), (3) comparison with anticholinergic agents, and (4) use in mechanically ventilated patients. The patient populations addressed are limited primarily to emergency department (ED) and intensive care/acute care settings. DATA SOURCES: English-language journal articles published between 1977 and 1993. STUDY SELECTION: Nine studies were evaluated that included beta-agonists alone or in combination with other bronchodilators in the treatment of acute exacerbation of COPD. Many of the studies contained design flaws or were limited in size, making interpretation difficult. In studies containing both asthma and COPD patients, focus was restricted to analysis of COPD patients when possible. DATA EXTRACTION: Performed subjectively by the authors. Studies were evaluated for methodologic strengths and weaknesses. DATA SYNTHESIS: Dosing studies in patients with stable disease show a relationship between dose and the various pulmonary function tests (PFTs). Dose also correlates with duration of action and incidence of adverse effects. Four studies compared NEBs versus MDISs. Studies revealed significant improvement in PFTs for both treatments, with no significant difference between groups noted. Five studies compared various combinations of beta-agonists and ipratropium. Both ipratropium and beta-agonists caused statistically significant increases in PFTs from baseline. Combination therapy provided no further increase in spirometry compared with that of single-agent therapy. One study did report an early discharge from the ED with the addition of ipratropium. Most studies did not use large doses of beta-agonists or evaluate the effect of repeated doses. Many studies allowed concomitant therapy. Most did not include outcome measurements, such as ED length of stay, admission rates, hospital stay, or incidence of relapse. CONCLUSIONS: Dose—response studies in patients with stable disease suggest that doses of albuterol powder up to 1 mg may be tolerated safely, although use of repeated larger doses has not been well studied. Beta-agonists given by MDIS or NEB are equally effective in this setting. There is no apparent advantage to combined use of beta-agonist and ipratropium in the acute setting. Future research in this area should evaluate the use of larger or repeated doses of beta-agonists in the acute setting. Optimizing concurrent therapy and evaluating various patient outcomes should receive special attention in further investigations.
Pharmacists' Attitudes toward Adverse Drug Reaction Reporting in Hong Kong
Authors: Lee Kenneth K.C. , Chan Thomas Y.K. , Raymond Kenneth , Critchley Julian A.J.H. 
Published: January 2017

OBJECTIVE: To study the attitudes and knowledge of pharmacists in Hong Kong toward the reporting of adverse drug reactions (ADRs). METHODS: In December 1993, all pharmacists who were working in retail shops (n=230), hospitals (n=44), or outpatient clinics (n=12) in Hong Kong were sent a questionnaire as well as a letter explaining the purpose of the survey. RESULTS: One hundred and twenty-nine pharmacists (retail pharmacies 40.4 percent, hospitals 68.2 percent, outpatient clinics 50 percent) responded. Although 93 percent of the pharmacists in this survey agreed that it is necessary to report ADRs, a much smaller proportion (14.7 percent) had actually done so in the previous 12 months. Most pharmacists (87.4 percent) were not aware of any ADR reporting system in Hong Kong. There did not appear to be a relationship between ADR reporting and the length or place of practice, workload, or patient contact time. Severe or unusual ADRs and ADRs to new products were perceived to be significant enough to report. CONCLUSIONS: The great majority of pharmacists in Hong Kong agreed on the necessity of reporting ADRs. The lack of knowledge of an ADR reporting program might have led to nonreporting in the past. It is important that there be continuing efforts to promote ADR reporting programs.
Cyclosporine and Vancomycin Disposition During Continuous Venovenous Hemodiafiltration
Authors: Munar Myrna Y , Doyle Ian C , Meyer Mary M 
Published: January 2017

Objective: To report cyclosporine and vancomycin disposition during continuous venovenous hemodiafiltration (CVVHD) in a 41—year-old heart transplant patient while in the intensive care unit at a primary and tertiary care teaching hospital. Case Summary: The patient received a 60—mg infusion of cyclosporine over 24 hours and vancomycin 1 g over 1 hour. Blood samples subsequently were collected and analyzed using whole blood monoclonal radioimmunoassay and fluorescence polarization immunoassay, respectively. Blood samples were measured every hour from the arterial and venous lines of the apparatus, as were ultrafiltrate drug concentrations. Drug clearance rates into the ultrafiltrate subsequently were calculated. Discussion: Measurements of ultrafiltrate detected no cyclosporine. A slight variation existed between arterial and venous drug concentrations, which was not statistically significant (p > 0.05, paired Student's t-test). Analysis of vancomycin samples revealed a steady decline of drug concentration, with 4.75% of the dose eliminated in the ultrafiltrate. Vancomycin arterial and venous concentrations decreased from 24.4 and 23.3 mg/L to 15.7 and 12.3 mg/L, respectively. Conclusions: Vancomycin is eliminated by CVVHD and it may be necessary for these patients to receive the drug more frequently. In contrast, cyclosporine is not removed effectively by CVVHD; therefore, replacement doses are not warranted.
Clinafloxacin-Theophylline Drug Interaction
Authors: Matuschka Paul R , Vissing Richard S 
Published: January 2017

Objective: To report an apparent pharmacokinetic interaction between clinafloxacin and theophylline in a patient with chronic obstructive pulmonary disease (COPD). Case Summary: A patient with a history of COPD was admitted for a fracture of the right femoral neck. Admission medications included extended-release theophylline 400 mg bid. The initial serum theophylline concentration was 81.03 µmol/L (normal 55—110). A subsequent concentration was subtherapeutic (46.62 µmol/L) and the theophylline dosage was increased to 300 mg tid. Therapeutic steady-state concentrations were achieved. The patient later developed pneumonia and was enrolled in a study of nosocomial acquired pneumonia involving clinafloxacin versus ceftazidime. He was randomized to receive clinafloxacin 200 mg iv ql2h. After clinafloxacin therapy was initiated, the serum theophylline concentration increased into the toxic range (155.96 µmol/L). Theophylline administration was held for 2 doses and the dosage then reduced to 200 mg tid. Serum concentrations decreased to within the therapeutic range. Discussion: The fluoroquinolones have been shown to interact with the hepatic metabolism of theophylline and increase serum theophylline concentrations. The quinolone metabolite, 4-oxo-quinolone, inhibits the N-demethylation of theophylline, leading to a decrease in the clearance of theophylline. The resultant rise in theophylline concentrations corresponds with the decrease in clearance and possible toxicity. In our patient, careful monitoring of theophylline concentrations and dosage adjustments resulted in the restoration of therapeutic serum concentrations. Conclusions: The observation of this drug interaction between clinafloxacin and theophylline suggests a need for prudent monitoring of theophylline concentrations. Dosage adjustments may be warranted when this combination of medications is used. Such action may prevent significant toxicities and prolonged hospitalization. Further controlled clinical trials in healthy volunteers are needed to substantiate the interaction between clinafloxacin and theophylline.
Sinus Arrest After Administration of Intravenous Metoclopramide
Authors: Malkoff Marc D , Ponzillo John J , Myles Geraldine L , Gomez Camilo R , Cruz-Flores Salvador 
Published: January 2017

Background: Sinus arrest is a rare complication of metoclopramide administration. Case Description: A 51-year-old woman developed Guillain-Barre syndrome and severe dysautonomia. Metoclopramide was administered for the treatment of gastroparesis. Sinus arrest followed drug administration on several occasions and on rechallenge. Conclusions: After reviewing the literature and discussing possible etiologies for this unusual adverse drug reaction in this setting, we recommend that metoclopramide be used with caution in patients prone to develop bradyarrythmias, particularly those with dysautonomias and Guillain-Barre syndrome.