bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Evaluation of the Safety and Efficacy of HMG-CoA Reductase Inhibitor Monotherapy in the Treatment of Primary Hypercholesterolemia
Authors: Hsu Irene , Spinier Sarah A , Johnson Nelda E 
Published: January 2017

Objective: To evaluate the comparative efficacy and safety of the 4 currently available hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, fluvastatin, lovastatin, pravastatin, and simvastatin, in the treatment of primary hypercholesterolemia. Data Sources: English-language clinical studies, abstracts, and review articles identified from MEDLINE searches and bibliographies of identified articles. Unpublished data were obtained from the Food and Drug Administration in accordance with the Freedom of Information Act. Study Selection: Placebo-controlled and comparative studies of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia. Data Extraction: Pertinent studies were selected and the data were synthesized into a review format. Data Synthesis: The chemistry, pharmacology, and pharmacokinetics of the 4 HMG-CoA reductase inhibitors are reviewed. Clinical trials evaluating the hypocholesterolemic efficacy of the HMG-CoA reductase inhibitors are examined, and results on the comparative efficacy and safety of these agents are summarized. On a milligram-per-milligram basis, simvastatin is twice as potent as lovastatin and pravastatin. The hypocholesterolemic effects of fluvastatin appear to be approximately 30% less than that of lovastatin. In posttransplant patients receiving cyclosporine, safety has been documented for low doses of lovastatin and simvastatin, but when a higher dosage of an HMG-CoA reductase inhibitor is warranted, pravastatin should be considered the drug of choice because of a lower incidence of myopathy. Relevant data on the incidence of adverse effects are presented. Pertinent outcomes data from clinical trials evaluating the effect of HMG-CoA reductase inhibitors on atherosclerosis regression and coronary mortality, as well as published economic analyses of cholesterol-lowering agents, are summarized. Recommendations on the selection of an HMG-CoA reductase inhibitor in various clinical situations are provided. Conclusions: The literature supports the comparable safety and tolerability of all 4 currently available HMG-CoA reductase inhibitors. Therefore, the choice of an HMG-CoA reductase inhibitor should depend on the extent of cholesterol lowering needed to meet the recommended treatment goal established by the National Cholesterol Education Program. Direct comparative studies are needed to confirm the relative, long-term cost-effectiveness of the various HMG-CoA reductase inhibitors in the treatment of primary hypercholesterolemia.
Therapeutic Approaches for Aids-Related Toxoplasmosis
Authors: Behbahani Roya , Moshfeghi Mersedeh , Baxter John D 
Published: January 2017

Objective: To summarize current knowledge of prophylaxis and treatment of AIDS-related toxoplasmosis. Data Sources: A MEDLINE search (1985-1994) was used to identify pertinent literature, including reviews. Study Selection and Data Extraction: All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion. Data Synthesis: Trimethoprim/sulfamethoxazole (TMP/SMX) appears to be useful for prophylaxis against toxoplasmosis in patients with AIDS. The most effective TMP/SMX dose for prevention of toxoplasmosis needs to be determined. Dapsone in combination with pyrimethamine therapy may be an effective alternative for toxoplasmosis prophylaxis. The most effective regimen for the treatment of AIDS-related toxoplasmosis is the combination therapy of pyrimethamine/sulfadiazine. In patients who cannot tolerate sulfadiazine therapy because of adverse effects or allergy, pyrimethamine with clindamycin therapy may be considered as a second-line alternative. Lifelong suppressive therapy is required after either treatment regimen to prevent relapse. Other newer agents such as azithromycin, clarithromycin, atovaquone, or trimetrexate-leucovorin need further studies to confirm their true effectiveness in the treatment of toxoplasmosis. Conclusions: TMP/SMX remains a useful agent in prophylaxis against toxoplasmosis. Pyrimethamine/sulfadiazine is the most effective combination in the treatment of acute toxoplasmosis.
Effect of Standard-Dose Trimethoprim/Sulfamethoxazole on the Serum Potassium Concentration in Elderly Men
Authors: Witt James M , Koo Ji M , Danielson Byron D 
Published: January 2017

OBJECTIVE: To determine the effect of standard-dose trimethoprim/sulfamethoxazole (TMP/SMX) (TMP 160 mg and SMX 800 mg q12h) on the serum potassium concentration. DESIGN: Retrospective and concurrent study. SETTING: A Veterans Affairs Medical Center. PATIENTS: Fifty-three men hospitalized at the Fargo Veterans Affairs Medical Center. Thirty-three patients who received standard-dose TMP/SMX for 3 or more days comprised the study group. Twenty patients who received oral cephradine or amoxicillin for 3 or more days comprised the control group. Patients who received potassium supplements, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, nonsteroidal antiinflammatory drugs, beta-blockers, heparin, known nephrotoxic agents, patients with a serum creatinine concentration of more than 177 μmol/L, and patients with baseline hyperkalemia (serum potassium concentration>5.1 mmol/L) were excluded. RESULTS: The serum potassium concentration in the study group was 4.22 ± 0.40 mmol/L and increased by 0.31 ± 0.38 mmol/L at the end of therapy (p < 0.001). Twenty-six patients in the study group (78.8%) had an increase in the serum potassium concentration during TMP/SMX therapy. Fourteen of these patients had follow-up serum potassium concentrations obtained after completion of therapy. The serum potassium concentration returned to baseline in 10 of these patients. The serum creatinine concentration also increased during therapy. However, the correlation between the increase in the serum potassium concentration and the increase in the serum creatinine concentration was weak (Pearson r = 0.29). The serum potassium in the control group was 4.34 mmol/L and remained essentially unchanged during therapy. CONCLUSIONS: Therapy with standard-dose TMP/SMX is associated with a slight increase in the serum potassium concentration. Routine monitoring of the serum potassium concentration in patients who are treated with standard-dose TMP/SMX therapy is unnecessary. However, TMP/SMX should be considered as a possible cause of unexplained hyperkalemia in elderly patients receiving TMP/SMX therapy.
Use of Pharmacy Computer Prescription Database to Access Hypertensive Patients for Mailed Survey Research
Authors: Beto Judith A , Listecki Robert E , Meyer Donald A , Budhy Richard J , Bansal Vinod K 
Published: January 2017

OBJECTIVE: To evaluate the use of a pharmacy computer prescription database (PCPD) to identify and sample hypertensive patients outside of their treatment setting for mailed, self-administered survey research comparing the presence and lack of participation incentives and mailed follow-up reminders. SETTING: Two independent, privately owned, free-standing community pharmacies. PARTICIPANTS: A total of 735 individuals identified from a PCPD search who had been prescribed at least 1 of 130 PCPD medications potentially used in hypertensive therapy. METHODS: PCPD was searched by the pharmacist/owner per protocol; participants were sent an individually addressed cover letter on pharmacy letterhead signed by the pharmacist that requested voluntary anonymous completion of an enclosed self-administered, quality-of-life opinion survey; the first search used no incentive or follow-up; die second search used an incentive and mailed a follow-up reminder. Research protocol followed published ethics guidelines. RESULTS: There was a mean 84% return with incentive and follow-up strategies compared with a mean 25% return without strategies (p < 0.01) for all drug groups between searches; no statistical difference in response was shown between the same drug groups (alpha1-blockers, calcium-channel blockers, and centrally acting alpha2-agonists) within searches. CONCLUSIONS: Acceptable response rates (74–93% return) can be obtained with traditional follow-up mailed incentives, prescription issuance within 6 months, incentives to both hypertensive and nonhypertensive responders, and sampling strategies within potential drug groups. Methodology can be adapted to other populations by alternative drug sampling strategies.
Hypersensitivity Reactions to Etoposide
Authors: Hoetelmans Richard MW , Schornagel Jan H , ten Bokkel Huinink Wim W , Beijnen Jos H 
Published: January 2017

OBJECTIVE: To report a hypersensitivity reaction to etoposide occurring in a patient after 2 months of drug therapy. CASE SUMMARY: a 20-year-old man with a diagnosis of testicular carcinoma was treated with bleomycin, etoposide, and cisplatin (BEP regimen). After dose 20 of etoposide, an exanthema was noted, which was attributed to etoposide. The patient had received 19 doses of etoposide during the previous 2 months without any sign of an allergic reaction. Rechallenging the patient with etoposide from another batch resulted in recurrence of the exanthema. DISCUSSION: Both etoposide and its excipient (polysorbate 80) are suspected of causing hypersensitivity reactions. Although the exact mechanism of the hypersensitivity reaction is not known, it is believed to be of nonimmunogenic origin. CONCLUSIONS: With a lower rate of infusion of etoposide and/or by premedication with antihistamines and/or corticosteroids, hypersensitivity reactions to etoposide might be prevented in patients with a history of hypersensitivity to this drug.
Aprotinin
Authors: Robert Sylvie , Wagner Bertil KJ , Boulanger Michelle , Richer Monique 
Published: January 2017

OBJECTIVE: To review the clinical pharmacology of aprotinin in patients undergoing surgical procedures involving major blood loss, namely, coronary artery bypass graft (CABG). DATA SOURCES: A MEDLINE search was used to identify French-and English-language publications on aprotinin using the indexing terms aprotinin, cardiothoracic surgery, and hemorrhage. The MEDLINE search was supplemented by review of article bibliographies. Data also were obtained from the approved Canadian and US product labels. STUDY SELECTIONS: All abstracts and uncontrolled and controlled clinical trials were reviewed. DATA EXTRACTION: Study design, population, results, and safety information were retained. Efficacy conclusions were drawn from controlled trials. DATA SYNTHESIS: Aprotinin, a serine protease inhibitor isolated from bovine lung tissue, decreases bleeding after cardiac surgery by mechanisms including antifibrinolytic activity and preservation of platelet function. Several trials have shown that aprotinin reduced blood loss and transfusion requirements in patients undergoing CABG. Its use in other surgical procedures involving major blood loss has been reported. Aprotinin is well tolerated, with minor allergic reactions being the most frequently reported adverse effect. Although unsubstantiated, the possibility that aprotinin could create a prothrombic state leading to early graft occlusion and formation of microthrombi in renal and coronary vasculatures is of concern. CONCLUSIONS: Aprotinin is an effective hemostatic agent in CABG. Clear definitions of indications, dosing, safety, and repeated use remain to be investigated thoroughly.
Phenytoin Protein Binding and Dosage Requirements during Acute and Convalescent Phases following Brain Injury
Authors: Markowsky Susan J , Skaar Debra J , Christie Joan M , Eyer Steven D , Ehresman David J 
Published: January 2017

OBJECTIVE: TO longitudinally evaluate unbound and total serum Phenytoin concentrations during intravenous phenytoin maintenance dosage and to determine the relationship among phenytoin protein binding, serum albumin, and unbound fatty acid concentrations in patients with head injuries during intensive care unit (ICU) and convalescent care. DESIGN: Serum albumin and phenytoin unbound fraction were determined twice weekly during ICU and convalescent care in 10 patients receiving phenytoin following acute brain injury. Phenytoin protein binding was also determined in 10 healthy control subjects. MAIN OUTCOME MEASURES: Longitudinal serum phenytoin concentrations associated with dosage adjustments targeted to achieve unbound phenytoin serum concentrations between 1.0 and 2.0 mg/L were documented during ICU and convalescent care. Longitudinal phenytoin protein binding was correlated with serum albumin and unbound fatty acid concentrations in neurotrauma patients. RESULTS: ICU patients received intravenous therapy for a mean of 15.0 days. The mean ± SD initial phenytoin intravenous dosage regimen of 6.0 ± 0.7 mg/kg/d resulted in mean ± SD total and unbound phenytoin concentrations of 3.2 ± 2.3 and 0.3 ± 0.2 mg/L. Two patients had seizures associated with low phenytoin concentrations. Four patients continued to receive oral phenytoin therapy during convalescent care; phenytoin dosage requirements decreased over time in these patients. During acute and convalescent care, the phenytoin unbound fraction ranged from 6.0% to 18.3% and correlated with albumin (r2 = 0.61, p < 0.0001) but did not correlate with unbound fatty acid concentrations. The mean phenytoin unbound fraction was 10.1% and 8.9% for the ICU and convalescent patients with brain injuries, respectively, and was 7.0% for the healthy volunteers. CONCLUSIONS: Phenytoin protein binding was significantly correlated with albumin and was more variable in ICU and convalescent patients with brain injuries than in healthy volunteers. The high dosage requirements and subtherapeutic unbound phenytoin concentrations observed during acute care are best explained by increased metabolism. Phenytoin dosage requirements decreased during convalescence.
Serum-Sickness-Like Reaction Associated with Minocycline Therapy in Adolescents
Authors: Harel Liora , Arnir Jacob , Livni Ella , Straussberg Rachel , Varsano Itzhak 
Published: January 2017

OBJECTIVE: TO describe a serum-sickness-like reaction in five adolescents treated with minocycline. CASE SUMMARY: Five adolescents developed a rash and arthralgias/arthritis after taking minocycline for 10-30 days. Symptoms resolved gradually after the medication was stopped. DISCUSSION: Serum sickness is not described in the pharmacology literature as an adverse effect of minocycline, and in the English literature there are only two case reports. The migration inhibitory factor assay and mast cell degranulation test were positive in four of the five patients. The results of these assays were consistent with a role for minocycline in causing these reactions. CONCLUSIONS: Clinicians should be aware of the possibility of serum-sickness-like reaction as an adverse effect of minocycline.
Vinorelbine: A New Antineoplastic Drug for the Treatment of Non-Small-Cell Lung Cancer
Authors: Jones Suzanne Fields , Burris Howard A 
Published: January 2017

OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, clinical activity, adverse effects, and dosage and administration guidelines for vinorelbine in the treatment of non-small-cell lung cancer (NSCLC). DATA SOURCES: A MEDLINE search (1989–1995) using the terms vinorelbine and Navelbine was conducted. Additional unpublished data were provided by Glaxo Wellcome Drug Information. STUDY SELECTION AND DATA EXTRACTION: The articles chosen for inclusion all appeared in peer-reviewed journals. Pertinent abstracts, as judged by the authors, were also included. DATA SYNTHESIS: Vinorelbine is a new semisynthetic vinca alkaloid approved by the Food and Drug Administration for the first-line treatment of patients with advanced NSCLC. The drug demonstrated a broad spectrum of antitumor activity in preclinical studies and produced dose-limiting neutropenia in Phase I trials. In Phase II studies, an overall response rate of approximately 30% was reported with single-agent vinorelbine. Furthermore, in large, multicenter, randomized Phase III trials, treatment with vinorelbine alone and in combination with cisplatin resulted in improved survival compared with controls. The drug was well tolerated, with granulocytopenia being the most commonly reported adverse effect. However, the incidence of fever and hospitalization associated with this granulocytopenia was exceptionally low. The recommended dose is 30 mg/m2 weekly administered by intravenous injection or infusion. CONCLUSIONS: As no specific chemotherapy regimen has previously been regarded as standard therapy for advanced NSCLC, vinorelbine is a promising new treatment for this patient population. It has been shown in several randomized, controlled trials to increase survival without compromising quality of life.
Cost Comparison of Recombinant Human Erythropoietin and Blood Transfusion in Cancer Chemotherapy-Induced Anemia
Authors: Sheffield Reinée E , Sullivan Sean D , Saltiel Emmanuel , Nishimura Lyn 
Published: January 2017

OBJECTIVE: To compare the cost of recombinant human erythropoietin (rHuEPO) with that of blood transfusion in the treatment of chemotherapy-induced anemia from a healthcare system perspective. DESIGN: A decision analytic model. Baseline estimates were obtained from a review of clinical trials data and economic evaluation studies. SUBJECTS: Secondary data analyses of patients with advanced malignancies, excluding hematologic malignancies and metastasized solid tumors. INTERVENTIONS: Patients received either leukocyte-depleted packed red blood cells (PRBCs) or rHuEPO 150 units/kg sc three times per week for 6 months (24 wk). After 6 weeks, if rHuEPO recipients did not display a response, they received rHuEPO 300 units/kg sc three times weekly for the duration of therapy. If rHuEPO recipients still exhibited no response, they were given blood transfusions. MEASUREMENTS AND MAIN RESULTS: For a treatment period of 24 weeks, approximately 64% of rHuEPO recipients responded at an average expected cost of $12 971 per patient. One hundred percent of transfusion recipients responded at a cost of $4481; this resulted in a cost savings of $8490. Variation of response rates for rHuEPO or PRBCs did not appreciably lower costs. Lower rHuEPO dosages and higher numbers of transfused units of PRBCs yielded approximately equivalent costs; however, these strategies may not be clinically prudent. CONCLUSIONS: From a healthcare system cost and outcome perspective, blood transfusion is the preferred strategy for chemotherapy-induced anemia. However, rHuEPO may be considered an effective blood-sparing alternative for patients with non-stem cell disorders. Future cost-effectiveness analyses are needed to assess more completely both the clinical and quality-of-life benefits rHuEPO may contribute to individual patients' lives and to society overall.
Mexiletine in the Symptomatic Treatment of Diabetic Peripheral Neuropathy
Authors: Wright Julie M , Oki Julie C , Graves Leland 
Published: January 2017

OBJECTIVE: To evaluate the efficacy and safety of mexiletine in the symptomatic treatment of diabetic peripheral neuropathy (DPN). METHODS: In this prospective, double-blind study, 29 patients were randomized to receive mexiletine 600 mg/d or matching placebo for 3 weeks. A four-item symptom score (FIS), which rated pain, dysesthesias, paresthesias, and nightly exacerbations of symptoms, and a 100-mm visual analog scale (VAS), which rated pain intensity, were completed by patients before and after treatment. At the end of treatment independent patient and investigator global assessments were made. Patients reported adverse effects after 1 and 3 weeks of treatment. RESULTS: Treatment groups were similar at baseline. The difference between the median changes in FIS scores (mexiletine = 5.5, placebo = 2) was not statistically significant. Overall symptom response was similar in both treatment groups as demonstrated by both global assessments (p = 0.19). The mean change in VAS score from baseline to posttreatment was determined for both groups and the difference between these mean scores was 16.5 mm (95% CI, −7.1 to 40.2 mm) (p = 0.16). Inadequate statistical power (1 — β = 0.40) may have resulted from small sample size, small magnitude of effect, or variability in the measured effect. Adverse effects were more common in the mexiletine group, though not statistically significant. One patient receiving mexiletine was hospitalized for palpitations. CONCLUSIONS: Because of conflicting reports of mexiletine's efficacy in the treatment of symptomatic DPN, this drug should be reserved for patients unresponsive or intolerant to standard therapy, without evidence of heart disease, and with sensations of burning, heat, formication, or stabbing pain.
Clinical Investigation of Topical Antimicrobials in Healthy Volunteers
Authors: Langford Jane H , Benrimoj Shalom I 
Published: January 2017

OBJECTIVE: To evaluate the antibacterial activity, onset of action, and duration of action of four topical antimicrobial gels containing cetrimide, bacitracin, polymyxin B sulfate, and a placebo gel. DESIGN: Multiples (1×, 2×, 4×, 8×) of minimally inhibitory in vitro drug concentrations were formulated in a gel vehicle. Antibacterial activity was evaluated using a scrub-wash methodology on artificially inoculated skin over an 8-hour study period. SETTING AND PARTICIPANTS: Healthy volunteers with intact forearm skin participated in the study. A standardized culture of Staphylococcus aureus NCTC 6571 was applied to four areas on each forearm, randomly assigned topical treatments were applied, and sites were sampled at predetermined time intervals using a surfactant wash fluid. OUTCOME MEASURES: Recovered bacteria were quantitated, allowing a comparison of antibacterial activity. RESULTS: Two-way and one-way ANOVA and a Scheffe test confirmed significant differences in antibacterial effect between the formulations containing 4 and 8 times the minimally inhibitory in vitro concentrations and placebo (p < 0.05). Duration of action was similar for all preparations; however, onset appeared to be faster with the formulations containing 4 and 8 times minimally inhibitory in vitro concentrations. CONCLUSIONS: The two topical preparations containing 4 and 8 times the minimally inhibitory in vitro concentrations of cetrimide, bacitracin, and polymyxin B sulfate demonstrated significant antibacterial activity and may have potential for further clinical investigations.